pulmicort and Asthma

The GINA recommends inhaled corticosteroids (ICSs) for the treatment of steps 2-3 of childhood asthma. However, the difference in efficacy between these drugs remains unclear. The purpose of this study was to compare the efficacy of different ICS drugs in the treatment of childhood asthma.. We searched PubMed and EMBASE for randomized controlled trials of ICSs in the treatment of childhood asthma. Using forced expiratory volume in the first second (FEV. Six studies involving 2237 children that reported FEV. In this study, the efficacy of three ICS drugs was quantitatively compared, providing necessary information for the implementation of medication guidelines for steps 2-3 of asthma in children.. This study analyzed the entire time-course of the drug efficacy of Inhaled corticosteroids in the treatment of asthma in children aged 5-12, which found that although the maximum efficacy of both ciclesonide and budesonide was the same, the onset speed of ciclesonide was faster than that of budesonide. The above information provides the necessary quantitative information for the implementation of medication guidelines for steps 2-3 asthma in children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Fluticasone; Humans

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans

Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary.. ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma.. Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Glucocorticoids; Humans

Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies.. We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios.. A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence.. In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Fluticasone; Humans

Current treatment for moderate-severe asthma with inhaled corticosteroid (ICS)-based therapy can follow two strategies: a single inhaler maintenance and reliever therapy (MART) regimen, or regular dosing with ICS/long-acting β. A systematic literature review (SLR) and meta-analysis was conducted to identify specific patient traits that may predict improved clinical outcomes with regular dosing or MART.. The SLR identified 28 studies in patients with moderate-severe asthma assessing regular dosing or MART treatments and reporting the traits and outcomes of interest. Network meta-regressions found no significant difference in the relative efficacy of regular dosing as compared with MART on any of the clinical outcomes (exacerbation rate, time to first exacerbation, FEV. The analysed patient traits evaluated in this study were associated with similar efficacy for the analysed outcomes to either regular dosing or MART; however, trends from the data observed encourage future analyses for possible identification of additional traits, or a combination of traits, that may be of interest. More comparable reporting of clinically important traits and outcomes would improve future analyses.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Ethanolamines; Formoterol Fumarate; Humans; Network Meta-Analysis

This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and pulmonary function in children with cough variant asthma (CVA). Five electronic databases were searched for studies about MKST+BUD therapy and BUD alone therapy on inflammation and pulmonary function in CVA children from inception to November 23, 2021. Twenty-two articles were included. The results showed that, compared with BUD alone, the combination treatment could achieve better improvement of pulmonary function and lower levels of inflammation (MKST+BUD group: FEV1: SMD = 2.77, 95% CI: 2.07, 3.46; FVC: SMD = 2.54, 95% CI: 1.82, 3.27; PEF: SMD = 2.27, 95% CI: 1.79, 2.75; IgE: SMD = -7.95, 95% CI: -9.66, -6.25; TNF-α: SMD = -4.67, 95% CI: -6.04, -3.31; IL-8: SMD = -8.18, 95% CI: -11.46, -4.90; BUD alone group: FEV1: SMD = 1.83, 95% CI: 1.34, 2.31; FVC: SMD = 1.39, 95% CI: 0.93, 1.84; PEF: SMD = 1.51, 95% CI: 1.13, 1.89; IgE: SMD = -4.93, 95% CI: -6.14, -3.72; TNF-α: SMD = -2.78, 95% CI: -3.76, -1.80; IL-8: SMD = -4.94, 95% CI: -7.10, -2.79). To conclude, compared with BUD alone, MKST+BUD therapy was found to be more effective in improving pulmonary function and reducing inflammation in CVA children. Key Words: Montelukast, Budesonide, Cough variant asthma, Children, Pulmonary function, Inflammatory markers, Meta-analysis.

Topics: Asthma; Budesonide; Child; Cough; Humans; Immunoglobulin E; Inflammation; Interleukin-8; Tumor Necrosis Factor-alpha

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Treatment Outcome

Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma.. We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratios with 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled.. AZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

Topics: Adolescent; Aged; Anti-Asthmatic Agents; Asthma; Azithromycin; Budesonide; Child; Disease Progression; Forced Expiratory Volume; Humans

The 2020 focused updates to the asthma management guidelines by the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group advocate for inhaled corticosteroid (ICS)-formoterol combinations as single maintenance and reliever therapy (SMART) for patients with persistent asthma. We review the rationale, the evidence supporting SMART use in asthma, and barriers limiting its wide adoption in the United States.. A growing body of evidence supports the use of SMART over the conventional use of controller medicaments with an as-needed short-acting β2 agonist for rescue therapy for the purpose of reducing the risk of asthma exacerbation and maintaining asthma control in adolescents and adults with persistent disease. Lack of US Food and Drug Administration approval, inconsistent insurance coverage, and limited options of ICS-formoterol combination available for use as SMART represent obstacles to wider integration of SMART in clinical practice.. SMART represents a paradigm shift in asthma management. By identifying and addressing the current and anticipated barriers to implementing SMART, its adoption by providers is likely to increase in the United States.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Drug Therapy, Combination; Formoterol Fumarate; Humans; United States

The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever.. To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma.. For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever.. Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher.. Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021.. The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression.. Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85).. In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Female; Formoterol Fumarate; Humans; Male; Randomized Controlled Trials as Topic

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans

To evaluate the effectiveness and practicality of single maintenance and reliever therapy (SMART) in the treatment of asthma exacerbation.. PubMed, MEDLINE, Cochrane, and Clinical Trial databases using the keywords SMART therapy, maintenance and reliever therapy, and budesonide and formoterol.. Articles were selected based on their relevance and applicability to this topic.. Multiple studies have evaluated the efficacy of SMART in reducing asthma exacerbations in comparison to standard inhaled corticosteroid maintenance and short-acting beta-agonist rescue therapy. Most of the randomized trials demonstrated a reduction in asthma exacerbation with open-label studies revealing similar effectiveness in reducing asthma exacerbation. Previously, concerns have been raised regarding the administration of increased doses of long-acting beta-agonist that may potentially mask symptoms and delay appropriate medical attention. However, studies have not demonstrated an increase in morbidity or mortality. The primary concern regarding many of these trials is that they have been sponsored by pharmaceutical companies.. Although not all studies demonstrated the effectiveness of SMART, most revealed a substantial reduction in asthma exacerbation frequency and severity.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Treatment Outcome

The claimed functional basis for ICSs in asthma and COPD is airway selectivity, attained by inhaling a potent, lipophilic compound with long local dissolution/absorption time. The development has been empirically based, resulting in five widely used ICSs. Among them, budesonide (BUD) deviates by being less lipophilic, leading to a more rapid systemic uptake with plasma peaks with some systemic anti-inflammatory activity. By this, BUD fits less well into the current pharmacological dogma of optimal ICS profile. In this review we compared the physicochemical, pharmacological and clinical properties of BUD, fluticasone propionate (FP) and fluticasone furoate (FF), representing different levels of lipophilicity, airway and systemic kinetics, focusing on their long-acting β2-agonist (LABA) combinations, in line with current GINA and GOLD recommendations. We are aware of the differences between formoterol (FORM) and the not rapid acting LABAs such as e.g. salmeterol and vilanterol but our comparisons are based on currently available combination products. A beclomethasone dipropionate (BDP)/FORM combination is also commented upon. Based on clinical comparisons in asthma and COPD, we conclude that the BUD/formoterol (BUD/FORM) combination is as effective and safe as the FP and FF combinations, and is in some cases even better as it can be used as "maintenance plus reliever therapy" (MART) in asthma and as maintenance in COPD. This is difficult to explain by current views of required ICS's/LABAs pharmacokinetic profiles. We propose that BUD achieves its efficacy by a combination of airway and systemic activity. The airway activity is dominating. The systemic activity contributes by plasma peaks, which are high enough for supportive anti-inflammatory actions at the blood and bone marrow levels but not sufficiently long to trigger a similar level of systemic adverse effects. This may be due to BUD's capacity to exploit a systemic differentiation mechanism as programmed for cortisol's various actions. This differentiation prospect can be reached only for an ICS with short plasma half-life. Here we present an alternative mode for an ICS to reach combined efficacy and safety, based on a poorly investigated and exploited physiological mechanism. A preference of this mode is broader versatility, due to that its straighter dose-response should allow a better adaptation to disease fluctuations, and that its rapid activity enables use as "anti-inflammatory reliever".

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive

Daily inhaled corticosteroid (ICS) and long-acting beta-2-agonist (LABA) combinations comprising either regular maintenance therapy with ICS/LABA plus as-needed short-acting beta-2-agonist (SABA) or ICS-formoterol combinations used as maintenance and reliever therapy (MART) are recommended for moderate asthma. This analysis compares the direct costs of twice-daily fluticasone propionate/salmeterol (FP/salm) and budesonide/formoterol MART in three Southeast Asian countries.. A literature review identified three randomized trials in patients with asthma (≥ 12 years) comparing regular twice-daily FP/salm with as-needed SABA versus MART in moderate asthma: AHEAD (NCT00242775/17 countries/2309 patients), COMPASS (AstraZeneca study SD-039-0735/16 countries/3335 patients), and COSMOS (AstraZeneca study SD-039-0691/16 countries/2143 patients). Economic analyses, conducted from a healthcare sector perspective (medication costs + healthcare utilization costs), applied unit costs from countries where healthcare costs are publicly available: Indonesia, Thailand and Vietnam. Results are expressed in British pound sterling (GBP/patient/year).. Annual exacerbation rates were low and differences between treatment strategies were small (range, FP/salm: 0.31-0.38, MART: 0.24-0.25) although statistically significant in favor of MART. Total average (minimum-maximum) direct costs (in GBP/patient/year) across the three studies were £187 (£137-£284), £158 (£125-£190), and £151 (£141-£164) for those who used FP/salm, and £242 (£217-£267), £284 (£237-£340) and £266 (£224-£315) for MART in Indonesia, Thailand and Vietnam, respectively. On average, total direct costs/patient/year with FP/salm were 22.8%, 44.6% and 43.0% lower than with MART for Indonesia, Thailand and Vietnam, respectively.. In the three countries evaluated, total treatment costs with regular twice-daily FP/salm were consistently lower than with budesonide/formoterol MART due to lower direct healthcare costs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Formoterol Fumarate; Health Care Costs; Humans; Indonesia; Thailand; Vietnam

In people with mild asthma poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. The use of fixed-dose combination inhalers containing an inhaled corticosteroid (ICS) and a fast-acting β. To evaluate the efficacy and safety of single combined FABA/ICS inhaler only used as needed in people with mild asthma.. Cochrane meta-analysis of available trial data.. Children aged 12+ and adults with mild asthma.. We searched the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE and Embase, ClinicalTrials.gov and the WHO trials portal on 19 March 2021.. A single fixed-dose FABA/ICS inhaler used as required compared with no treatment, placebo, short-acting beta agonist (SABA) as required, regular ICS with SABA as required, regular fixed-dose combination ICS/long-acting beta agonist (LABA), or regular fixed-dose combination ICS/FABA with as required ICS/FABA.We included randomised controlled trials (RCTs) and cross-over trial. We excluded trials shorter than 12 weeks. We included full texts, abstracts and unpublished data.. We used Cochrane's standard methodological procedures and applied the GRADE approach to assess the evidence.. We included six studies from which 9657 participants contributed to the meta-analyses. All used dry powder budesonide and formoterol as the combination inhaler. Two studies included children aged 12+ years and two studies were open-label.. Compared with as-required FABA alone, as-required FABA/ICS reduced exacerbations requiring systemic steroids (OR 0.45, 95% CI 0.34 to 0.60, 2 RCTs, 2997 participants, high-certainty evidence), equivalent to 109 people out of 1000 in the FABA alone group experiencing an exacerbation requiring systemic steroids, compared with 52 (95% CI 40 to 68) out of 1000 in the FABA/ICS as-required group. FABA/ICS as required may also reduce the odds of an asthma-related hospital admission or emergency department or urgent care visit (OR 0.35, 95% CI 0.20 to 0.60, 2 RCTs, 2997 participants, low-certainty evidence). Changes in asthma control were small and less than the minimal clinically important difference (MCID). FABA/ICS as required was associated with reductions in fractional exhaled nitric oxide, probably reducing the odds of an adverse event (OR 0.82, 95% CI 0.71 to 0.95) and may reduce total systemic steroid dose (mean difference (MD) -9.90, 95% CI -19.38 to -0.42).. There may be little or no difference in the number of people with asthma exacerbations requiring systemic steroids with FABA/ICS as required compared with regular ICS (OR 0.79, 95% CI 0.59 to 1.07, 4 RCTs, 8065 participants, low-certainty evidence), equivalent to 81 people out of 1000 in the regular ICS plus FABA group experiencing an exacerbation requiring systemic steroids, compared with 65 (95% CI 49 to 86) out of 1000 in the FABA/ICS as-required group. The odds of an asthma-related hospital admission or emergency department or urgent care visit may be reduced in those taking FABA/ICS as required (OR 0.63, 95% CI 0.44 to 0.91, 4 RCTs, 8065 participants, low-certainty evidence). Changes in asthma control were small and less than MCID. Adverse events and total systemic corticosteroid doses were similar between groups. FABA/ICS as required was likely associated with less average daily exposure to ICS than those on regular ICS (MD -154.51 mcg/day, 95% CI -207.94 to -101.09).. FABA/ICS as required is clinically effective in adults and adolescents with mild asthma and reduced exacerbations, hospital admissions or unscheduled healthcare visits and exposure to systemic corticosteroids and probably reduces adverse events compared with FABA as required alone. FABA/ICS as required is as effective as regular ICS and reduced asthma-related hospital admissions or unscheduled healthcare visits, and average exposure to ICS, and is unlikely associated with increased adverse events.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Humans; Nebulizers and Vaporizers

For decades, short acting beta agonists (SABAs) have been prescribed for giving symptomatic relief to asthmatics. However, this symptomatic benefit perceived by the patient leads to the overuse and dependency of the patient to the SABA inhaler and underusage of the inhaled corticosteroid (ICS) containing controller inhalers resulting in destabilizing disease control and increased risk of exacerbations. In order to address this issue, the 2019 update of the Global Initiative for Asthma (GINA) strategy document no longer recommends the use of SABA inhalers as the preferred reliever for asthma due to concerns around poor outcomes and safety. Instead, it strongly supports the use of a combined ICS-fast acting beta agonist as a reliever also termed as an Anti-inflammatory Reliever Therapy (AIR). In this review we discuss the extent of SABA overusage and its impact on asthma outcomes, the resultant change in the recommendations in the GINA document and finally the evidence supporting the use of formoterol- budesonide as AIR therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Formoterol Fumarate; Humans

The efficacy of inhaled budesonide for managing moderate-to-severe acute exacerbations in children is not clear. Therefore, this study aimed to evaluate hospital admission rates, need for use of systemic corticosteroids, length of hospital stay and adverse events when inhaled budesonide is added to standard pediatric emergency department management of moderate-to-severe acute exacerbations of asthma.. A systematic search was conducted in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases. Randomized controlled trials that evaluated the effect of nebulized budesonide in moderate-to-severe acute exacerbations of asthma in pediatric patients were included for this meta-analysis. Statistical analysis was done using STATA version 13.0.. A total of 16 RCTs were included. Children receiving nebulized budesonide had 43% lower risk of being hospitalized (RR 0.57; 95% CI, 0.39; 0.85) and 66% lower risk of requiring systemic corticosteroids (RR 0.34; 95 % CI, 0.21; 0.55) compared with those receiving placebo. There were no differences in the length of hospital stay (Hedges's g standardized mean difference - 1.53; 95% CI, - 3.64; 0.58) and risk of adverse events (RR 0.87, 95% CI; 0.65; 1.17) between the two groups. There was no evidence of publication bias for any of the outcomes considered.. The findings of this meta-analysis support the use of inhaled budesonide in reducing risk of hospitalization and the need for systemic corticosteroids among children with acute moderate-to-severe asthma exacerbation.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Emergency Service, Hospital; Hospitalization; Humans; Length of Stay; Randomized Controlled Trials as Topic

Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.. To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.. We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021.. We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.. Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.. Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-rel. Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Asthma affects 350 million people worldwide including 45% to 70% with mild disease. Treatment is mainly with inhalers containing beta₂-agonists, typically taken as required to relieve bronchospasm, and inhaled corticosteroids (ICS) as regular preventive therapy. Poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. Fixed-dose combination inhalers containing both a steroid and a fast-acting beta₂-agonist (FABA) in the same device simplify inhalers regimens and ensure symptomatic relief is accompanied by preventative therapy. Their use is established in moderate asthma, but they may also have potential utility in mild asthma.. To evaluate the efficacy and safety of single combined (fast-onset beta₂-agonist plus an inhaled corticosteroid (ICS)) inhaler only used as needed in people with mild asthma.. We searched the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, ClinicalTrials.gov and the World Health Organization (WHO) trials portal. We contacted trial authors for further information and requested details regarding the possibility of unpublished trials. The most recent search was conducted on 19 March 2021.. We included randomised controlled trials (RCTs) and cross-over trials with at least one week washout period. We included studies of a single fixed-dose FABA/ICS inhaler used as required compared with no treatment, placebo, short-acting beta agonist (SABA) as required, regular ICS with SABA as required, regular fixed-dose combination ICS/long-acting beta agonist (LABA), or regular fixed-dose combination ICS/FABA with as required ICS/FABA. We planned to include cluster-randomised trials if the data had been or could be adjusted for clustering. We excluded trials shorter than 12 weeks. We included full texts, abstracts and unpublished data.. Two review authors independently extracted data. We analysed dichotomous data as odds ratios (OR) or rate ratios (RR) and continuous data as mean difference (MD). We reported 95% confidence intervals (CIs). We used Cochrane's standard methodological procedures of meta-analysis. We applied the GRADE approach to summarise results and to assess the overall certainty of evidence. Primary outcomes were exacerbations requiring systemic steroids, hospital admissions/emergency department or urgent care visits for asthma, and measures of asthma control.. We included six studies of which five contributed results to the meta-analyses. All five used budesonide 200 μg and formoterol 6 μg in a dry powder formulation as the combination inhaler. Comparator fast-acting bronchodilators included terbutaline and formoterol. Two studies included children aged 12+ and adults; two studies were open-label. A total of 9657 participants were included, with a mean age of 36 to 43 years. 2.3% to 11% were current smokers. FABA / ICS as required versus FABA as required Compared with as-required FABA alone, as-required FABA/ICS reduced exacerbations requiring systemic steroids (OR 0.45, 95% CI 0.34 to 0.60, 2 RCTs, 2997 participants, high-certainty evidence), equivalent to 109 people out of 1000 in the FABA alone group experiencing an exacerbation requiring systemic steroids, compared to 52 (95% CI 40 to 68) out of 1000 in the FABA/ICS as-required group. FABA/ICS as required may also reduce the odds of an asthma-related hospital admission or emergency department or urgent care visit (OR 0.35, 95% CI 0.20 to 0.60, 2 RCTs, 2997 participants, low-certainty evidence). Compared with as-required FABA alone, any changes in asthma control or spirometry, though favouring as-required FABA/ICS, were small and less than the minimal clinically-important differences. We did not find evidence of differences in asthma-associated quality of life or mortality. For other secondary outcomes FABA/ICS as required was associated with reductions in fractional exhaled nitric oxide, probably reduces the odds of an adverse event (OR 0.82, 95% CI 0.71 to 0.95, 2 RCTs, 3002 participants, moderate-certainty evidence) and may reduce total systemic steroid dose (MD -9.90, 95% CI -19.38 to -0.42, 1 RCT, 443 participants, low-certainty evidence), and with an increase in the daily inhaled steroid dose (MD 77 μg beclomethasone equiv./day, 95% CI 69 to 84, 2 RCTs, 2554 participants, moderate-certainty evidence). FABA/ICS as required versus regular ICS plus FABA as required There may be little or no difference in the number of people with asthma exacerbations requiring systemic steroid with FABA/ICS as required compared with regular ICS (OR 0.79, 95% CI 0.59 to 1.07, 4 RCTs, 8065 participants, low-certainty evidence), equivalent to 81 people out of 1000 in the regular ICS plus FABA group experiencing an exacerbation requiring systemic steroids, compared to 65 (95% CI 49 to 86) out of 1000 FABA/ICS as required group. The odds of an asthma-related hospital admission. We found FABA/ICS as required is clinically effective in adults and adolescents with mild asthma. Their use instead of FABA as required alone reduced exacerbations, hospital admissions or unscheduled healthcare visits and exposure to systemic corticosteroids and probably reduces adverse events. FABA/ICS as required is as effective as regular ICS and reduced asthma-related hospital admissions or unscheduled healthcare visits, and average exposure to ICS, and is unlikely to be associated with an increase in adverse events. Further research is needed to explore use of FABA/ICS as required in children under 12 years of age, use of other FABA/ICS preparations, and long-term outcomes beyond 52 weeks.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Disease Progression; Drug Combinations; Formoterol Fumarate; Hospitalization; Humans; Nebulizers and Vaporizers; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Terbutaline

Acute asthmatic exacerbation in children causes economic burdens both directly and indirectly. The GINA guideline does mention the use of inhaled or oral corticosteroids in the treatment of asthmatic exacerbation, it provides little practical guidance on the use of nebulized corticosteroid.. To review and recommend the practical considerations in the use of nebulized corticosteroid in children with acute asthmatic exacerbation.. This consensus was developed by a group of expert pediatricians in respiratory and allergy fields in Thailand. The recommendations were made based on a review of published studies and clinical opinions. The eligible studies were confined to those published in English, and randomized controlled trials and meta-analyses involving nebulized corticosteroids in asthmatic exacerbation in children aged between 1-18 years.. There were 13 randomized controlled-trial studies published from 1998 to 2017. Nine of the 13 studies compared nebulized with systemic corticosteroid conducted in moderate to severe exacerbation, while the remaining four compared nebulized corticosteroid with placebo conducted in mild to severe exacerbation. The admission rate was significantly lower in severe exacerbation (one study) and pooled four mild to severe exacerbation studies comparing with placebo (p 0.022). Other clinical parameters were significantly improved with nebulized corticosteroid such as clinical scores, systemic corticosteroid/bronchodilator use, or shorter ER stays. Only one study used fluticasone, while the other 12 studies conducted by budesonide (92.31%).. Nebulized corticosteroid may offer an effective therapeutic option for the management of acute exacerbation of asthma in all severities. Nebulized budesonide is the preferred corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Consensus; Humans; Infant

Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aimed to clarify the role of NebCSs in children 5 years or younger for the management of acute asthma exacerbations, asthma maintenance therapy, and the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children 5 years or younger, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of 40 or more participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCSs to be at least as efficacious as oral corticosteroids in the emergency room for the management of mild to moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCSs are effective and well tolerated in patients 5 years or younger for the management of acute and chronic asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Respiratory Sounds

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dry Powder Inhalers; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive

This study was aimed to evaluate the beneficial role of inhalation budesonide(BUD) in improving the pulmonary functions, and reducing the hospital admission rate, worsening of asthma and commonly encountered adverse events in pediatric asthma.. The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases to identify the randomized control trials(RCTs).. 21 RCTs involving 12,787 subjects were included. The meta-analysis revealed that the BUD has reduced the hospitalization rate (Mantel-Haenszel (M-H), random effects odd ratio (RE-OR) of 0.34, p = 0.003, I. The outcomes of the meta-analysis suggest that high-dose inhalation BUD could benefit the pediatric patients in minimizing the worsening of asthma and hospitalization rate, along with improving the pulmonary functions, with negligible adverse drug reactions.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Emergency Service, Hospital; Hospitalization; Humans; Otitis Media; Randomized Controlled Trials as Topic; Sinusitis; Treatment Outcome

Despite improvements in medications, devices and understanding of the disease, about half of all asthma patients worldwide remain inadequately controlled, suggesting the need for a new approach to asthma management. Poor adherence to prescribed maintenance therapy and over-reliance on SABA reliever medication is a common cause of inadequate control. This article reviews published data from 6- to 12-month, double-blind, RCT and open-label real-world studies involving budesonide/formoterol maintenance and reliever therapy (MART) and relevant comparator approaches to asthma management, and considers how these compare in achieving the treatment goals described in guidelines. The data confirm that patients with asthma treated with budesonide/formoterol MART achieved the same or better asthma symptom control compared with ICS/LABA plus SABA regimens at similar or higher ICS doses, with consistently lower rates of exacerbations and considerably lower annual requirement for oral corticosteroids. These findings have been confirmed across a range of severities of persistent asthma. With the MART approach, maintenance dosing ensures coverage for day-to-day control, and the use of a reliever with anti-inflammatory properties (budesonide/formoterol) provides extra doses of ICS as soon as symptoms prompt the use of reliever, resulting in a 40-50% reduction of exacerbations compared with an ICS-based treatment approach plus as-needed SABA as reliever. As-needed, budesonide/formoterol has also recently been shown to be more effective as a reliever in mild asthma than SABA alone, reducing exacerbations by up to 64% in the SYGMA studies.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Female; Formoterol Fumarate; Humans; Maintenance Chemotherapy; Male

Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Electronic Nicotine Delivery Systems; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Tropanes

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Child; Clinical Trials as Topic; Eosinophilia; Forced Expiratory Volume; Humans; Sputum; Surveys and Questionnaires; Tiotropium Bromide

Topics: Asthma; Budesonide; Formoterol Fumarate; Humans

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Fluticasone; Glucocorticoids; Humans; Infant; Mometasone Furoate; Pregnenediones

Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.. To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.. We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.. We selected parallel-group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.. At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta-analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random-effects model for meta-analyses. We did not perform planned subgroup analyses due to there being too few included trials.. We included six randomized trials involving 1199 children aged from 4 to 12 years (per-protocol population: 1008), with mild-to-moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon-metered dose inhaler (CFC-MDI) at an equivalent dose (MD -0.44 cm/year, 95% CI -1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).. This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head-to-head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real-life observational studies seem more attractive and feasible.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluticasone; Growth; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Time Factors

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Humans; Risk Factors; United Kingdom

Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma.. To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma.. The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017. Two reviewers selected randomized clinical trials or observational studies evaluating SMART vs inhaled corticosteroids with or without a LABA used as the controller therapy and short-acting β-agonists as the relief therapy for patients aged 5 years or older with persistent asthma and reporting on an outcome of interest.. Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs), risk differences (RDs), and mean differences with corresponding 95% CIs. Citation screening, data abstraction, risk assessment, and strength of evidence grading were completed by 2 independent reviewers.. Asthma exacerbations.. The analyses included 16 randomized clinical trials (N = 22 748 patients), 15 of which evaluated SMART as a combination therapy with budesonide and formoterol in a dry-powder inhaler. Among patients aged 12 years or older (n = 22 524; mean age, 42 years; 14 634 [65%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.68 [95% CI, 0.58 to 0.80]; RD, -6.4% [95% CI, -10.2% to -2.6%]) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.77 [95% CI, 0.60 to 0.98]; RD, -2.8% [95% CI, -5.2% to -0.3%]). Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy. Among patients aged 4 to 11 years (n = 341; median age, 8 [range, 4-11] years; 69 [31%] were female), SMART was associated with a reduced risk of asthma exacerbations compared with a higher dose of inhaled corticosteroids as the controller therapy (RR, 0.55 [95% CI, 0.32 to 0.94]; RD, -12.0% [95% CI, -22.5% to -1.5%]) or the same dose of inhaled corticosteroids and LABA as the controller therapy (RR, 0.38 [95% CI, 0.23 to 0.63]; RD, -23.2% [95% CI, -33.6% to -12.1%]).. In this meta-analysis of patients with persistent asthma, the use of single maintenance and reliever therapy compared with inhaled corticosteroids as the controller therapy (with or without a long-acting β-agonist) and short-acting β-agonists as the relief therapy was associated with a lower risk of asthma exacerbations. Evidence for patients aged 4 to 11 years was limited.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Bias; Budesonide; Delayed-Action Preparations; Drug Therapy, Combination; Formoterol Fumarate; Humans; Maintenance Chemotherapy; Risk Assessment

Asthma affects about 300 million individuals worldwide. Although most patients have mild disease, the majority of them do not have good control and are at risk of exacerbations. Poor compliance with regular maintenance treatment is a considerable problem and is believed to be the main reason for poor control in asthma. In patients with moderate to severe asthma, maintenance and as-needed treatment with one inhaler containing an inhaled corticosteroid (ICS) and the long-acting inhaled β2-agonist formoterol has been proved effective in reducing the risk of severe exacerbations. Recently, the results of 2 large double-blind randomized trials assessing the use of as-needed budesonide/formoterol in patients with mild asthma, who had indications for a regular controller treatment, were published. In comparison with as-needed terbutaline treatment, as-needed budesonide/formoterol treatment improved symptom control and reduced the risk of exacerbations. In comparison with regular ICS treatment, exacerbation rates were similar, but regular treatment schedule was associated with better asthma control (despite a higher cumulative ICS dose). The results of these trials have shown that as-needed budesonide/formoterol therapy has acceptable efficacy in mild asthma and may be viewed as a therapeutic option for these patients. As-needed treatment may be preferred by patients who fear the side effects of ICS treatment or by those who experience difficulty in following a fixed-dose regimen. Patients with mild asthma wishing to achieve optimal asthma control may prefer regular maintenance treatment with an ICS.

Topics: Administration, Inhalation; Asthma; Budesonide; Disease Management; Formoterol Fumarate; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

Many trials have been published comparing inhaled corticosteroid (ICS) treatments in asthma. However, mixed results necessitate the summarization of available evidence to aid in decision-making. Areas covered: This systematic review evaluated randomized controlled trials (RCTs) that compared the efficacy and safety of inhaled fluticasone propionate (FP) with other ICS including beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed was searched and 54 RCTs that fit pre-determined criteria were included. Endpoints evaluated included lung function, asthma symptom control, exacerbation frequency, reliever use, quality of life and steroid-related side effects. Expert commentary: Across all studies, FP was associated with either more favorable or at least similar efficacy and safety, in comparison with BDP or BUD. This observation may be related to FP's higher relative potency and almost negligible oral bioavailability. FP was comparable to CIC for efficacy. However, CIC appeared to have a smaller impact on cortisol levels than FP, which is likely due to CIC's incomplete conversion to active metabolite (des-CIC) and the lower potency of des-CIC compared with FP. Although there were no significant differences in evaluated outcomes after treatment with different ICS in the majority of studies, some observed differences could be explained by their respective pharmacodynamic and pharmacokinetic properties.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Pregnenediones; Randomized Controlled Trials as Topic

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Budesonide; Disease Management; Drug Therapy, Combination; Formoterol Fumarate; Humans; Medication Adherence; Patient Satisfaction; Treatment Outcome

Maintenance treatment with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) is recommended for patients whose asthma is not controlled with a low-to-moderate dose of ICS alone; a separate reliever medication is used on an as-needed basis. The Gaining Optimal Asthma ControL (GOAL) study demonstrated that salmeterol/fluticasone maintenance treatment can improve asthma control and reduce future risk compared with fluticasone alone, although the dose escalation design of this study meant that most patients treated with salmeterol/fluticasone were receiving the highest dose of ICS at the end of the study. Similarly, budesonide/formoterol maintenance therapy improved asthma control and reduced future risk compared with budesonide alone in the Formoterol and Corticosteroids Establishing Therapy (FACET) study. An alternative approach to asthma management is to use an ICS/LABA for both maintenance and reliever therapy. A large body of clinical evidence has shown that the use of budesonide/formoterol in this way improves both current control and reduces future risk compared with ICS/LABA plus as-needed short-acting β2-agonist (SABA), even when patients receive lower maintenance doses of ICS as part of the maintenance and reliever therapy regimen. In addition, one study has shown that beclometasone/formoterol maintenance and reliever therapy reduces exacerbations more effectively than beclometasone/formoterol plus as-needed SABA. The use of ICS/LABA as both maintenance and reliever therapy ensures that an increase in reliever use in response to worsening symptoms is automatically matched by an increase in ICS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Humans

Fixed dose combinations (FDC) of inhaled corticosteroid (ICS) and long-acting beta agonist (LABA) are well established in asthma treatment. The budesonide/salmeterol (B/S) FDC is now about to reach the market. It is provided as powder in hard capsules of two strengths: 120/20μg and 240/20μg when expressed as delivered doses, equivalent to 150/25μg and 300/25μg when expressed as nominal doses. Its development involved 9 pharmacokinetic (320 subjects), 3 phase II (123 subjects) and 4 phase III (1206 patients with different asthma severity) studies. Delivery is effectuated via low resistance inhaler device, Axahaler®, generating also fine particles targeting the small airways. B/S safety, assessed in 1401 subjects, did not outline novel concerns specific for this FDC. In conclusion, the B/S dry powder FDC can be used for asthma treatment in adults not adequately controlled on ICS alone, or to maintain control of ICS/LABA treated patients, in whom switching to alternative FDC is indicated.

Topics: Adrenergic beta-2 Receptor Agonists; Asthma; Budesonide; Clinical Trials as Topic; Drug Combinations; Drug Evaluation, Preclinical; Glucocorticoids; Humans; Nebulizers and Vaporizers; Salmeterol Xinafoate

One of the most widely used fixed combinations in asthma management is dry powder budesonide+formoterol fumarate dihydrate which is commercially available as Symbicort Turbuhaler(®) (and generic products), Easyhaler Bufomix(®) and DuoRespSpiromax(®) inhaler. The aim of this paper was to review the fixed dry powder combination of inhaled budesonide+formoterol fumarate dihydrate for asthma treatment in adolescents and adults.. A literature search using relevant search terms, reference lists for reviews and meta-analyses was performed.. In symptomatic adolescent and adult patients with asthma maintenance and reliever therapy with a single-inhaler fixed combination of dry powder budesonide+formoterol fumarate dihydrate is an evidenced option. The combination treatment is convenient to patients. It reduces the number of exacerbations requiring treatment with oral corticosteroids. In some patients the strategy may also reduce the total intake of inhaled corticosteroids over time. Whether important outcome measures of asthma treatment, such as hospital admission and emergency room visit rates, may be reduced is less well documented since the published studies may have been influenced by publication bias. Non-pharmaceutical company-sponsored research evaluating such measures is needed. There is no evidence for the use of single inhaler fixed combinations of inhaled corticosteroids+long-acting β(2)-agonists in children (<12 years of age), and budesonide+formoterol fumarate dihydrate should not be prescribed to the age group.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Formoterol Fumarate; Hospitalization; Humans; Nebulizers and Vaporizers

Inhaled glucocorticoids are the mainstay of asthma treatment. Indeed, such therapeutic agents effectively interfere with many pathogenic circuits underpinning asthma. Among these drugs, during the last decades budesonide has been probably the most used molecule in both experimental studies and clinical practice. Therefore, a large body of evidence clearly shows that budesonide, either alone or in combination with long-acting bronchodilators, provides a successful control of asthma in many patients ranging throughout the overall spectrum of disease severity. These excellent therapeutic properties of budesonide basically depend on its molecular mechanisms of action, capable of inhibiting within the airways the activity of multiple immune-inflammatory and structural cells involved in asthma pathobiology.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Glucocorticoids; Humans; Severity of Illness Index

To evaluate the therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma.. The databases CNKI, Wanfang Data, VIP, PubMed, EMbase, and BioMed Central were searched for randomized controlled trials (RCTs) of montelukast sodium combined with budesonide in the treatment of children with cough variant asthma. Data extraction and quality assessment were performed for RCTs which met the inclusion criteria, and RevMan 5.3 software was used to perform quality assessment of the articles included and Meta analysis.. A total of 11 RCTs involving 1 097 patients were included. The results of the Meta analysis showed that compared with the control group (inhalation of budesonide alone), the observation group (inhalation of montelukast sodium combined with budesonide) had significantly higher overall response rate and more improved pulmonary function parameters including forced expiratory volume in the first second, percentage of forced expiratory volume in the first second, and peak expiratory flow, as well as significantly lower recurrence rate (P<0.01). The incidence of adverse events showed no significant difference between the two groups.. Inhalation of montelukast sodium combined with budesonide has a significant effect in children with cough variant asthma and does not increase the incidence of adverse events.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cough; Cyclopropanes; Drug Therapy, Combination; Humans; Quinolines; Sulfides

Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth.. We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic.. We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65).. Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Body Height; Budesonide; Child; Child Development; Child, Preschool; Humans

Sublingual immunotherapy (SLIT) for house dust mite (HDM) allergy has an evidence of efficacy demonstrated by meta-analyses, but marked differences are reported between the various SLIT products. The standardized quality (SQ) HDM sublingual tablet containing Dermatophagoides pteronyssinus and Dermatophagoides farinae in a 1:1 ratio (MK-8237) is a qualitative advance for SLIT products.. The rationale for developing the HDM tablets is discussed against the other available SLIT products, analyzing the clinical data on efficacy and safety obtained by controlled trials.. Following preliminary Phase I and II studies, a double-blind, placebo-controlled trial on 604 patients with mite-induced asthma, aged more than 14 years and treated by inhaled budesonide, was performed using one of three active doses (1, 3 or 6 SQ) or placebo. The results showed a significant mean difference between 6 SQ-HDM and placebo in the reduction in daily budesonide dose of 81 µg (p = 0.004), with relative mean and median reductions of 42 and 50% for 6 SQ-HDM and 15 and 25% for placebo, respectively. Safety was very good, with no report of anaphylactic reaction. These findings suggest a role to the HDM SLIT tablets in the treatment of patients with mite-induced asthma.

Topics: Animals; Asthma; Bronchodilator Agents; Budesonide; Humans; Pyroglyphidae; Sublingual Immunotherapy; Tablets

The recommended treatment of mild asthma is regular maintenance inhaled corticosteroids (ICSs) with a short-acting β-agonist as a separate inhaler used when needed for symptom relief. However, the benefits of regular ICS use in actual clinical practice are limited by poor adherence and low prescription rates. An alternative strategy would be the symptom-driven (as-required or "prn") use of a combination ICS/short-acting β-agonist or ICS/long-acting β-agonist inhaler as a reliever rather than regular maintenance use. The rationale for this approach is to titrate both the ICS and β-agonist dose according to need and enhance ICS use in otherwise poorly adherent patients who overrely on their reliever β-agonist inhaler. This strategy will only work if the β-agonist component has a rapid onset of action for symptom relief. There is evidence to suggest that this regimen has advantages over regular ICS therapy and might represent an effective, safe, and novel therapy for the treatment of intermittent and mild asthma. In this commentary we review this evidence and propose that randomized controlled trials investigating different combination ICS/β-agonist inhaler products prescribed according to this regimen in intermittent and mild asthma are an important priority.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Humans; Nebulizers and Vaporizers; Patient Compliance; Randomized Controlled Trials as Topic

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Disease Progression; Female; Glucocorticoids; Humans; Monitoring, Physiologic; Patient Education as Topic; Pregnancy; Pregnancy Complications; Respiratory Function Tests; Respiratory Physiological Phenomena; Risk; Severity of Illness Index; Smoking; Smoking Prevention; Theophylline

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians.. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma.. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014.. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma.. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation.. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision.. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses.Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence.. To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children.. We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinical study results.org were undertaken. Searches are up to date to 7 November 2012.. Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone.Ciclesonide compared to budesonide (dose ratio 1:2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group.Ciclesonide compared to fluticasone (dose ratio 1:1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00).Ciclesonide versus fluticasone (dose ratio 1:2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23).The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1:1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1:1). For ciclesonide versus fluticasone (dose ratio 1:2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1:2).. An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects.

Topics: Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Traditionally inhaled treatment for asthma has used separate preventer and reliever therapies. The combination of formoterol and budesonide in one inhaler has made possible a single inhaler for both prevention and relief of symptoms (single inhaler therapy or SiT).. To assess the efficacy and safety of budesonide and formoterol in a single inhaler for maintenance and reliever therapy in asthma compared with maintenance with inhaled corticosteroids (ICS) (alone or as part of current best practice) and any reliever therapy.. We searched the Cochrane Airways Group trials register in February 2013.. Parallel, randomised controlled trials of 12 weeks or longer in adults and children with chronic asthma. Studies had to assess the combination of formoterol and budesonide as SiT, against a control group that received inhaled steroids and a separate reliever inhaler.. We used standard methodological procedures expected by The Cochrane Collaboration.. We included 13 trials involving 13,152 adults and one of the trials also involved 224 children (which have been separately reported). All studies were sponsored by the manufacturer of the SiT inhaler. We considered the nine studies assessing SiT against best practice to be at a low risk of selection bias, but a high risk of detection bias as they were unblinded.In adults whose asthma was not well-controlled on ICS, the reduction in hospital admission with SiT did not reach statistical significance (Peto odds ratio (OR) 0.81; 95% confidence interval (CI) 0.45 to 1.44, eight trials, N = 8841, low quality evidence due to risk of detection bias in open studies and imprecision). The rates of hospital admission were low; for every 1000 people treated with current best practice six would experience a hospital admission over six months compared with between three and eight treated with SiT. The odds of experiencing exacerbations needing treatment with oral steroids were lower with SiT compared with control (OR 0.83; 95% CI 0.70 to 0.98, eight trials, N = 8841, moderate quality evidence due to risk of detection bias). For every 100 adults treated with current best practice over six months, seven required a course of oral steroids, whilst for SiT there would be six (95% CI 5 to 7). The small reduction in time to first severe exacerbation needing medical intervention was not statistically significant (hazard ratio (HR) 0.94; 95% CI 0.85 to 1.04, five trials, N = 7355). Most trials demonstrated a reduction in the mean total daily dose of ICS with SiT (mean reduction was based on self-reported data from patient diaries and ranged from 107 to 385 µg/day). Withdrawals due to adverse events were more common in people treated with SiT (OR 2.85; 95% CI 1.89 to 4.30, moderate quality evidence due to risk of detection bias).Three studies including 4209 adults compared SiT with higher dose budesonide maintenance and terbutaline for symptom relief. The studies were considered as low risk of bias. The run-in for these studies involved withdrawal of LABA, and patients were recruited who were symptomatic during run-in. The reduction in the odds of hospitalisation with SiT compared with higher dose ICS did not reach statistical significance (Peto OR; 0.56; 95% CI 0.28 to 1.09, moderate quality evidence due to imprecision). Fewer patients on SiT needed a course of oral corticosteroids (OR 0.54; 95% CI 0.45 to 0.64, high quality evidence). For every 100 adults treated with ICS over. Single inhaler therapy has now been demonstrated to reduce exacerbations requiring oral corticosteroids against current best practice strategies and against a fixed higher dose of inhaled steroids. The strength of evidence that SiT reduces hospitalisation against these same treatments is weak. There were more discontinuations due to adverse events on SiT compared to current best practice, but no significant differences in serious adverse events. Our confidence in these conclusions is limited by the open-label design of the trials, and by the unknown adherence to treatment in the current best practice arms of the trials.Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance ICS and separate relief medication. The reduced odds of exacerbations with SiT compared with higher dose ICS should be viewed in the context of the possible impact of LABA withdrawal during study run-in. This may have made the study populations more likely to respond to SiT.Single inhaler therapy is not currently licensed for children under 18 years of age in the United Kingdom and there is currently very little research evidence for this approach in children or adolescents.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Terbutaline

Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness and cough. Treatment with inhaled steroids and bronchodilators often results in good control of symptoms, prevention of further morbidity and mortality and improved quality of life. Several steroids and beta2-agonists (long- and short-acting) as well as combinations of these treatments are available in a single inhaler to be used once or twice a day, with a separate inhaler for relief of symptoms when needed (for patients in Step three or higher, according to Global Initiative for Asthma (GINA) guidelines). Budesonide/formoterol is also licenced for use as maintenance and reliever therapy from a single inhaler (SiT; sometimes referred to as SMART therapy). SiT can be prescribed at a lower dose than other combination therapy because of the additional steroid doses being received as reliever therapy. It has been suggested that using SiT improves compliance and hence reduces symptoms and exacerbations, but it is unclear whether it increases side effects associated with the use of inhaled steroids.. To assess the efficacy and safety of budesonide/formoterol in a single inhaler (SiT) to be used for both maintenance and reliever therapy in asthma in comparison with maintenance treatment provided through combination inhalers with a higher maintenance steroid dose (either fluticasone/salmeterol or budesonide/formoterol), along with additional fast-acting beta2-agonists for relief of symptoms.. We searched the Cochrane Airways Group Specialised Register of trials, online trial registries and drug company websites. The most recent search was conducted in November 2013.. We included parallel-group, randomised controlled trials of at least 12 weeks' duration. Studies were included if they compared single-inhaler therapy with budesonide/formoterol (SiT) versus combination inhalers at a higher maintenance dose of steroids than was given in the SiT arm (either salmeterol/fluticasone or budesonide/formoterol).. We used standard methods expected by The Cochrane Collaboration. Primary outcomes were exacerbations requiring hospitalisation, exacerbations requiring oral corticosteroids and serious adverse events (including mortality).. Four studies randomly assigning 9130 people with asthma were included; two were six-month double-blind studies, and two were 12-month open-label studies. No trials included children younger than age 12. Trials included more women than men, with mean age ranging from 38 to 45, and mean baseline steroid dose (inhaled beclomethasone (BDP) equivalent) from 636 to 888 μg. Mean baseline forced expiratory volume in one second (FEV1) percentage predicted was between 70% and 73% in three of the trials, and 96% in another. All studies were funded by AstraZeneca and were generally free from methodological biases, although the two open-label studies were rated as having high risk for blinding, and some evidence of selective outcome reporting was found. These possible sources of bias did not lead us to downgrade the quality of the evidence. The quantity of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups.Separate data for exacerbations leading to hospitalisations, to emergency room (ER) visits or to a course of oral steroids could not be obtained. Compared with higher fixed-dose combination inhalers, fewer people using SiT had exacerbations requiring hospitalisation or a visit to the ER (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57 to 0.90; I(2) = 0%, P = 0.66), and fewer had exacerbations requiring a course of oral corticosteroids (OR 0.75, 95% CI 0.65 to 0.87; I(2) = 0%, P = 0.82). This translates to one less person admitted to hospital or visiting the ER (95% CI 0 to 2 fewer) and two fewer people needing oral steroids (95% CI 1 to 3 fewer) compared with fixed-dose combination treatment with a short-acting beta-agonist (SABA) reliever (per 100 treated over eight months). No statistical heterogeneity was observed in either outcome, and the evidence was rated of high quality. Although issues with blinding were evident in two of the studies, and one study recruited a less severe population, sensitivity analyses did not change the main results, so quality was not downgraded.We could not rule out the possibility that SiT increased rates of serious adverse events (OR 0.92, 95% CI 0.74 to 1.13; I(2) = 0%, P = 0.98; moderate-quality evidence, downgraded owing to imprecision).We were unable to say whether SiT improved results for several secondary outcomes (morning and evening peak expiratory flow (PEF), rescue medication use, symptoms scales), and in cases where results were significan. SiT reduces the number of people having asthma exacerbations requiring oral steroids and the number requiring hospitalisation or an ER visit compared with fixed-dose combination inhalers. Evidence for serious adverse events was unclear. The mean daily dose of inhaled corticosteroids (ICS) in SiT, including the total dose administered with reliever use, was always lower than that of the other combination groups. This suggests that the flexibility in steroid administration that is possible with SiT might be more effective than a standard fixed-dose combination by increasing the dose only when needed and keeping it low during stable stages of the disease. Data for hospitalisations alone could not be obtained, and no studies have yet addressed this question in children younger than age 12.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Maintenance Chemotherapy; Male; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

Low-dose budesonide/formoterol combination used in the SMART fashion with symptom-reactive supplemental dosing has been reported to reduce asthma exacerbations as compared to the use of budesonide alone or to lower doses of budesonide/formoterol without supplemental dosing.. We undertook to review the non-exacerbation outcomes of SMART therapy and to assess the patient education implications of this treatment strategy.. Systematic review.. Patients treated with this strategy appear to be under-treated in that the majority fail to achieve guideline-defined control standards. The SMART strategy has not been tested against equivalent or higher doses of budesonide/formoterol given in symptom-prevention fashion. Existing educational strategies that focus on recognition of poor disease control may not be applicable with SMART therapy and the use of action plans has not been clarified with this symptom-reactive strategy. There is some evidence from that the current clinical use of SMART therapy may be contaminated frequently by the concurrent prescription of short-acting bronchodilators. There is no information on long-term outcomes with a symptom-reactive ICS/LABA strategy but the use of the strategy for one year has been associated with rising sputum and airway biopsy eosinophil counts.. Despite fewer severe exacerbations with SMART therapy as compared to ICS monotherapy or lower dose ICS/LABA therapy, the strategy produces poor day-to-day control of symptoms and is associated with increasing inflammation.. The symptom-reactive strategy described as SMART therapy is associated with poor symptom control of asthma.

Topics: Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers

The fraction of exhaled nitric oxide (FeNO) has gained interest as a non-invasive tool to measure airway inflammation in asthma since it reflects allergic inflammation. Recent controlled clinical studies have, however, questioned its role in the management of asthma in children. To assess the clinical value of FeNO in paediatric asthma management, a meta-analysis was performed on the controlled studies of childhood asthma management guided by repeated FeNO measurements, and relevant publications on the confounders of FeNO were reviewed. The data suggests that utilising FeNO to tailor the dose of inhaled corticosteroids in children cannot be recommended for routine clinical practice since there is a danger of excessive inhaled corticosteroid doses in children without meaningful changes in clinical outcomes. Many disease and non-disease related factors (most importantly atopy, height/age and infection) affect FeNO levels which can easily confound the interpretation.

Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Disease Management; Fluticasone; Humans; Nitric Oxide

A recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls.. The purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids.. A retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773).. In the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38-2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67-1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS.. Treatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Diabetes Mellitus; Double-Blind Method; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Hyperglycemia; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors

Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred therapy option for patients who do not achieve optimal control of their asthma with low-dose ICS monotherapy. In Europe, four ICS/LABA products are commercially available for asthma maintenance therapy (fluticasone propionate/formoterol fumarate, fluticasone propionate/salmeterol xinafoate, budesonide/formoterol fumarate and beclometasone dipropionate/formoterol fumarate), and other combinations are likely to be developed over the next few years (e.g. mometasone/formoterol fumarate, fluticasone furoate/vilanterol, mometasone/indacaterol). Data from randomized, controlled, clinical trials do not demonstrate a clear overall efficacy difference among ICS/LABA combinations approved for asthma therapy. Conversely, pharmacological data indicate that there may be certain advantages to using one ICS or LABA over another because of the specific pharmacodynamic and pharmacokinetic profiles associated with particular treatments. This review article summarizes the pharmacological characteristics oft he various ICSs and LABAs available for the treatment of asthma, including the potential for ICS and LABA synergy, and gives an insight into the rationale for the development of the latest ICS/LABA combination approved for asthma maintenance therapy.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Time Factors; Treatment Outcome

In mild asthma low-dose steroid inhalation treatment reduces severe exacerbations and exacerbation associated loss of lung function. In patients with mild asthma, symptom-driven use of a combination of inhaled steroid and short-acting beta-2-sympathomimetics in a single inhaler is feasible. In moderate and severe asthma the fixed combination of formoterol and budesonide can be used a maintenance therapy but also as treatment of acute symptoms. Monotherapy with long-acting beta 2-sympathomimetics should be completely avoided. Long-acting anticholinergic drugs are equally efficacious as long-acting beta-2-sympathomimetics, but have not yet been approved for use in patients with asthma. The correct identification of various phenotypes is especially important in severe asthma, because there are different specific treatment approaches.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Airway Resistance; Asthma; Bronchodilator Agents; Budesonide; Cholinergic Antagonists; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Feasibility Studies; Formoterol Fumarate; Humans; Long-Term Care; Respiratory Function Tests

Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART® Turbuhaler®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.. This is a post hoc analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.. At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) (plus short-acting β2-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.. BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Kaplan-Meier Estimate; Logistic Models; Lung; Male; Nebulizers and Vaporizers; Odds Ratio; Patient Selection; Practice Guidelines as Topic; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Time Factors; Treatment Outcome

Two recent trials from the National Heart, Lung, and Blood Institute's asthma clinical trials networks raise a concern about using double the dose of an inhaled corticosteroid (ICS) as a positive control arm in clinical trials of add-on therapy. The literature evaluating the response to doubling the dose of an ICS is briefly reviewed. The vast majority of studies do not demonstrate a significant positive benefit from doubling the dose of an ICS but do show improvement with 4-fold increases that is equal to or greater than that of add-on long-acting bronchodilators. It is recommended that doubling the dose of an ICS no longer be considered a positive comparator arm in clinical trials, although it might be beneficial in individual patients.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Clinical Trials as Topic; Glucocorticoids; Humans; Treatment Outcome

Guidelines for clinical practice are expected to gather evidence-based recommendations to support optimal medical behaviours. The aim of the current review is to explore how currently available research regarding the strategy of using budesonide/formoterol (BUD/FORM) as maintenance and reliever therapy (Symbicort SMART) covers the items considered by the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) system, through a comparative analysis of methodological approaches, clinical outcomes, patient-reported outcomes and costs, in order to highlight uncovered areas.. Thirteen trials providing data on 21 095 analysed patients were available. No serious limits in methodological study features were found. Evaluation of the clinical outcome was consistent with the efficacy of BUD/FORM maintenance and reliever therapy. As the time to first exacerbation was the primary outcome in most of the studies, conclusive indications cannot be drawn regarding other clinical outcomes or patient-reported outcomes, which were investigated as secondary outcomes. A comprehensive systematic review exploring all critical and important outcomes is desirable, but further research concerning the safety issues of Long Acting β2 Agonists (LABA) and patients' reported outcomes about the SMART in respect to alternative strategies is likely to affect a clear recommendation in the near future.. The efficacy of BUD/FORM maintenance and reliever therapy in extending the time to first exacerbation appears consistent between studies. Further studies exploring all patients' important outcomes are needed. Clinical and economic assessments are worthy of being investigated to verify the directness of the evidence in respect to real life patients and different geographical realities.

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bias; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Costs and Cost Analysis; Data Collection; Disease Progression; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Europe; Evidence-Based Medicine; Fluticasone; Formoterol Fumarate; Humans; Multicenter Studies as Topic; Patient Satisfaction; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Spirometry; Time Factors; Treatment Outcome; World Health Organization

Around 5.2 million people in the UK are estimated to have asthma.1 Mortality and hospitalisation rates associated with the condition fell significantly in the last 20 years of the 20th century, but have not fallen further since then.2 In 2006, there were over 1,000 asthma deaths and around 78,000 hospital admissions due to asthma in the UK.2 One pharmacological strategy that has been developed recently to try to improve asthma management is the use of single maintenance and reliever therapy (SMART). This involves the patient using a single inhaler containing a corticosteroid (budesonide) and a long-acting beta(2) agonist (LABA; formoterol), for regular maintenance treatment, but also for additional 'rescue' use on an as-needed basis. Combination inhaler use is claimed to improve adherence, and is now included in UK asthma guidelines.3 Here we assess the evidence for single combination therapy, its relative effectiveness in comparison with other approaches, and whether or under what circumstances it should be used.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Medication Adherence; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Long-acting beta-agonists are a common second line treatment in people with asthma inadequately controlled with inhaled corticosteroids. Single device inhalers combine a long-acting beta-agonist with an inhaled steroid delivering both drugs as a maintenance treatment regimen. This updated review compares two fixed-dose options, fluticasone/salmeterol FP/SALand budesonide/formoterol, since this comparison represents a common therapeutic choice.. To assess the relative effects of fluticasone/salmeterol and budesonide/formoterol in people with asthma.. We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Search results are current to June 2011.. We included randomised studies comparing fixed dose fluticasone/salmeterol and budesonide/formoterol in adults or children with a diagnosis of asthma. Treatment in the studies had to last for a minimum of 12 weeks.. Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.. Five studies met the review entry criteria (5537 adults). Study populations entered the studies having previously been treated with inhaled steroids and had moderate or mild airway obstruction (mean FEV(1) predicted between 65% and 84% at baseline). Most of the studies assessed treatment over a period of six months. The studies were at a low risk of selection and performance/detection bias, although we could not determine whether missing data had an impact on the results. Availablility of outcome data was satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral steroids was lower with fluticasone/salmeterol but did not reach statistical significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N = 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants requiring oral steroids, treatment with fluticasone/salmeterol would lead to between 25 fewer and seven more people per 1000 experiencing a course of oral steroids. Although the odds of hospital admission was higher with fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95% CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000 would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse event related to asthma was higher with fluticasone/salmeterol but did not differ significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies, 4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 13 more people per 1000 would experience a serious adverse event on fluticasone/salmeterol.Secondary outcomesLung function outcomes, symptoms, rescue medication, composite of exacerbations leading to either emergency department visit or hospital admission, withdrawals and adverse events did not differ statistically between treatments. Assessment of quality of life was limited to two studies, both of which gave results that did not reach statistical significance. One study reported one death out of 1000 participants on fluticasone/salmeterol and no deaths in a similar number of participants treated with budesonide/formoterol. No deaths were reported in the other studies.. Statistical imprecision in the effect estimates for exacerbations and serious adverse events do not enable us to conclude that either therapy is superior. The uncertainty around the effect estimates justify further trials to provide more definitive conclusions; the overall quality of evidence based on GRADE recommendations for the three primary outcomes and withdrawals due to serious adverse events was moderate. We rated the quality of evidence for mortality to be low. Results for lung function outcomes showed that the drugs were sufficiently similar that further research is unlikely to change the effects. No trials were identified in the under-12s and research in this population is a high priority. Evaluation of quality of life is a priority for future research.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Respiratory type-IV hypersensitivity reactions due to corticosteroids is a rare phenomenon. We describe two such cases. The first is a 37- year-old atopic woman who developed labial angioedema and nasal itching after the use of budesonide nasal spray. A month later, after the first puffs of a formoterol/budesonide spray prescribed for asthma, she noticed symptoms of tongue and oropharyngeal itching and redness with subsequent dysphagia, labial and tongue angioedema, and facial oedema. The second is a 15-year-old non-atopic woman who reported pruritic eruptions around the nostrils after using a budesonide nasal spray. A year later she presented with nasal pruritus with intense congestion and labial and facial oedema after using the same spray. Both patients were evaluated with patch-tests using the commercial T.R.U.E. test, a budesonide solution, and corticosteroid creams. Test evaluation was performed at 48 and 96 hours. In both patients, patch tests were positive to budesonide (++) on the second day. The first patient also had a positive (+) reaction to tixocortol-21-pivalate. All the other patch tests were negative. Clinicians should be aware that hypersensitivity reactions may occur during the use of nasal or inhaled corticosteroids.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Female; Humans; Patch Tests; Respiratory Hypersensitivity

The aim of asthma management is to gain and maintain asthma control and reduce the risk of future exacerbations. However, despite the availability of effective therapies and national and international guidelines for their use, many patients remain inadequately controlled and continue to endure and accept a reduced quality of life. This review discusses current challenges in asthma management facing primary care physicians and provides insight into new treatment strategies developed to improve asthma control. A web-based literature review was undertaken with a focus on studies and reviews discussing asthma control and management with traditional therapies and new therapies, including a novel treatment approach using budesonide/formoterol maintenance and reliever therapy. One of the most common problems in long-term asthma control is poor adherence to inhaled corticosteroid (ICS) maintenance therapy, resulting in under-treatment of inflammation. Many patients tend to over-rely on short-acting beta(2)-agonist medication for quick relief of symptoms at the expense of ICS therapy, thus lowering anti-inflammatory protection and increasing the propensity for the development of severe and potentially life-threatening exacerbations. New simplified treatment strategies have been investigated with the aim of overcoming many of these primary care challenges, ultimately improving asthma control and reducing the future risk of exacerbations.

Topics: Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Medication Adherence; Quality of Life

Asthma is a heterogeneous disease with various components that may contribute to symptoms. Obtaining global control of is one of the fundamental parts of the management of this disease.. The Cochrane trial database, Medline and Embase, were searched systematically, and approximately 20 respiratory journals and conference abstracts were searched manually. The search was limited to publications in English language of last 20 years and which included the keywords 'budesonide', 'formoterol', 'asthma' and 'control'.. The purposes of this review are: i) to discuss the rationale about possibility of using combination therapy administered with a single inhaler for both daily maintenance and relief as needed of breakthrough symptoms in asthma management; ii) to give readers the current status of clinical pharmacological treatment of asthma; iii) to discuss the evidence on the use of budesonide/formoterol dry powder in one inhaler.. Among the various inhalatory drugs, budesonide and formoterol can be conveniently delivered in one dry powder inhaler and simplify treatment by providing immediate step-up when symptoms increase. Alongside the anti-inflammatory component, formoterol provides both short- and long-acting bronchodilator effects with maintenance and reliever properties. The option of using one inhaler simplifies treatment by simultaneously providing bronchodilator and anti-inflammatory activity, thus enhancing compliance. As indicated in guidelines, all these characteristics are essential for optimizing asthma treatment and control.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Powders

An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in comparison with placebo in previous Cochrane reviews. This increase was significant in trials that did not randomise participants to an inhaled corticosteroid, but less certain in the smaller numbers of participants in trials that included an inhaled corticosteroid in the randomised treatment regimen.. We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol, when each are used with an inhaled corticosteroid as part of the randomised treatment.. Trials were identified using the Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol were also checked. The date of the most recent search was July 2009.. Controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid), and were of at least 12 weeks duration.. Two authors independently selected trials for inclusion in the review and extracted outcome data. Unpublished data on mortality and serious adverse events were sought from the sponsors and authors.. Eight studies met the eligibility criteria of the review recruiting 6,163 adults and adolescents. There were seven studies (involving 5,935 adults and adolescents) comparing formoterol and budesonide to salmeterol and fluticasone. All but one study administered the products as a combined inhaler, and most used formoterol 50 mcg and budesonide 400 mcg twice daily versus salmeterol 50 mcg and fluticasone 250 mcg twice daily. There were two deaths overall (one on each combination) and neither were thought to be related to asthma.There was no significant difference between treatment groups for non-fatal serious adverse events, either all-cause (Peto OR 1.14; 95% CI 0.82 to 1.59, I(2) = 26%) or asthma-related (Peto OR 0.69; 95% CI 0.37 to 1.26, I(2) = 33%). Over 23 weeks the rates for all-cause serious adverse events were 2.6% on formoterol and budesonide and 2.3% on salmeterol and fluticasone, and for asthma-related serious adverse events, 0.6% and 0.8% respectively.There was one study (228 adults) comparing formoterol and beclomethasone to salmeterol and fluticasone, but there were no deaths or hospital admissions.No studies were found in children.. The seven identified studies in adults did not show any significant difference in safety between formoterol and budesonide in comparison with salmeterol and fluticasone. Asthma-related serious adverse events were rare, and there were no reported asthma-related deaths. There was a single small study comparing formoterol and beclomethasone to salmeterol and fluticasone in adults, but no serious adverse events occurred in this study. No studies were found in children.Overall there is insufficient evidence to decide whether regular formoterol and budesonide or beclomethasone have equivalent or different safety profiles from salmeterol and fluticasone.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

To examine the efficacy of the maintenance and reliever (M+R) approach in the treatment of asthma exacerbations.. PubMed, MEDLINE, and Cochrane database searches using the key words formoterol and budesonide, dynamic dosing, adjustable dosing, and M+R therapy.. Articles were selected based on their relevance to the topic of this review.. Several studies have examined dynamic dosing of the long-acting beta-agonist formoterol combined with budesonide in the treatment of asthma. Most of these studies have shown reductions in asthma exacerbations. Although obvious concern arises regarding increase in dose of the long-acting beta-agonist component, no significant signal of morbidity or mortality has been seen. Potential concerns regarding the studies performed thus far include the fact that all have been sponsored by the pharmaceutical industry and have required beta-agonist response as an inclusion criterion.. Although many of the data regarding this approach are positive, not all the studies have demonstrated efficacy. It is hoped that future non-pharmaceutical company-sponsored research will clarify this issue and, should efficacy be confirmed, shed light on the mechanism of action.

Topics: Asthma; Budesonide; Controlled Clinical Trials as Topic; Drug Dosage Calculations; Drug Synergism; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans

To compare the effectiveness of budesonide/formoterol (Symbicort) for Maintenance and Reliever Therapy (Symbicort SMART) Turbuhaler with twice daily inhaled corticosteroid (ICS) treatment, alone or in combination with a long-acting beta(2)-agonist (LABA).. Meta analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with budesonide/formoterol for maintenance and relief had the equivalent, or up to fourfold higher, maintenance dose of ICS. The primary outcome was the incidence of severe exacerbation (oral glucocorticosteroid treatment for > or = 3 days, emergency visit and/or hospitalisation).. Of the seven RCTs available six met the inclusion criteria. Risk of severe exacerbations was significantly reduced: 41% vs. higher-dose budesonide alone [relative risk (RR) 0.59, 95% confidence interval (95% CI): 0.51-0.68, p < 0.00001]; 43% vs. equivalent dose budesonide/formoterol as maintenance twice daily (RR 0.57, 95% CI: 0.49-0.66, p < 0.00001); 24% vs. higher-dose salmeterol/fluticasone twice daily (RR 0.76, 95% CI: 0.64-0.90, p = 0.002); and 26% vs. higher-dose budesonide/formoterol twice daily (RR 0.74, 95% CI: 0.58-0.96, p = 0.02). Significant heterogeneity was not detected in the primary analyses (p > 0.1). Secondary analyses also demonstrated that budesonide/formoterol for maintenance and relief reduced the most severe exacerbations, resulting in less hospitalisations/accident and emergency visits than higher-dose budesonide, equivalent dose budesonide/formoterol and higher-dose salmeterol/fluticasone twice daily.. Budesonide/formoterol for maintenance and relief is significantly more effective at reducing severe exacerbations than higher-dose ICS alone, or in combination with a LABA. This has important implications for treating uncontrolled patients at steps 2 and 3 of the joint BTS/SIGN guidelines.

Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Hospitalization; Humans; Publication Bias; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome

Current asthma guidelines recommend the use of long-acting beta-agonists (LABAs) in combination with inhaled corticosteroids (ICSs) for long-term control and prevention of symptoms in persistent asthma. Data on the risk of asthma exacerbations of LABAs in combination with ICSs, as prescribed in typical clinical practice, are very scarce.. The authors conducted a systematic literature review and meta-analysis of observational studies to examine the risk of asthma exacerbations, measured as asthma-related hospitalization and/or asthma-related emergency room (ER) visits, in adults receiving LABAs plus ICSs in a fixed-dose combination compared with patients receiving ICSs alone.. Seven studies, all retrospective cohort studies conducted in the United States, representing approximately 96,000 patients, were included in the meta-analysis. The meta-analysis found that the use of ICSs plus LABAs was associated with a lower risk of asthma-related hospitalizations and/or ER visits than ICSs alone (odds ratio: 0.82; 95% confidence interval: 0.72-0.94). Sensitivity analyses to explore heterogeneity of endpoint definition, duration of follow-up, and patient characteristics did not significantly alter the findings.. Overall, this systematic meta-analysis suggests that patients in clinical practice treated with a single inhaler containing ICSs plus LABAs experience fewer asthma exacerbations than similar patients treated with ICSs alone.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Respiratory Function Tests

Budesonide/formoterol inhalation aerosol (Symbicort AstraZeneca, Wilmington, Delaware) is an inhaled corticosteroid (ICS) and long-acting beta(2)-adrenergic agonist (LABA) combination administered twice daily via one hydrofluoroalkane pressurized metered-dose inhaler (pMDI) approved in the United States for the long-term maintenance treatment of persistent asthma in patients >or=12 years of age whose asthma cannot be controlled by an ICS alone. The objective was to review efficacy, safety, and pharmacogenetic data on budesonide/formoterol pMDI in the treatment of persistent asthma.. The authors searched PubMed and respiratory meeting databases to identify asthma studies of budesonide/formoterol pMDI. Studies involving traditional and patient-reported outcomes, safety, tolerability, or pharmacogenetics were included.. In two 12-week pivotal trials in adolescents and adults, treatment with budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg) twice daily for moderate to severe persistent asthma or 80/4.5 microg x 2 inhalations (160/9 microg) twice daily for mild to moderate persistent asthma, demonstrated greater efficacy and similar tolerability compared with placebo and the same nominal dose of its monocomponents. Comparisons with formoterol dry powder inhaler (DPI) for predose forced expiratory volume in one second (FEV(1)) and with budesonide pMDI for 12-hour mean postdose FEV(1) demonstrated the anti-inflammatory and bronchodilatory contributions of budesonide and formoterol, respectively. Evaluations of patient-reported outcomes, including asthma-specific quality of life and treatment satisfaction, further supported the clinical benefits of budesonide/formoterol pMDI. In a 52-week tolerability study of patients aged >or=12 years, budesonide/formoterol pMDI was delivered at up to double the maximum dose (640/18 microg twice daily) and demonstrated a safety profile similar to that of budesonide (640 microg twice daily), with no unexpected pattern of abnormalities. Additional studies reported that budesonide/formoterol pMDI 320/9 microg twice daily and fluticasone propionate/salmeterol DPI 250/50 microg twice daily have similar efficacy and tolerability, with significantly more patients achieving >or=15% improvement in FEV(1) within 15 minutes with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI. Moreover, inheritance of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor does not appear to affect clinical outcomes with budesonide/formoterol pMDI.. Budesonide/formoterol pMDI administered twice daily is effective and generally well tolerated in patients whose asthma is not well controlled on ICS alone.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Clinical Trials as Topic; Delayed-Action Preparations; Drug Combinations; Ethanolamines; Glucocorticoids; Humans; Metered Dose Inhalers; Patient Satisfaction; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2

The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents.. A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed.. Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Canada; Child; Cromolyn Sodium; Cyclopropanes; Drug Prescriptions; Ethanolamines; Europe; Fluocinolone Acetonide; Fluticasone; Humans; Italy; Prevalence; Quinolines; Salmeterol Xinafoate; Sulfides; United States

The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting beta agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6-12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7-10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Patient Compliance; Randomized Controlled Trials as Topic; Treatment Outcome

Children who are referred to specialist care with asthma that does not respond to treatment (problematic severe asthma) are a heterogeneous group, with substantial morbidity. The evidence base for management is sparse, and is mostly based on data from studies in children with mild and moderate asthma and on extrapolation of data from studies in adults with severe asthma. In many children with severe asthma, the diagnosis is wrong or adherence to treatment is poor. The first step is a detailed diagnostic assessment to exclude an alternative diagnosis ("not asthma at all"), followed by a multidisciplinary approach to exclude comorbidities ("asthma plus") and to assess whether the child has difficult asthma (improves when the basic management needs, such as adherence and inhaler technique, are corrected) or true, therapy-resistant asthma (still symptomatic even when the basic management needs are resolved). In particular, environmental causes of secondary steroid resistance should be identified. An individualised treatment plan should be devised depending on the clinical and pathophysiological characterisation. Licensed therapeutic approaches include high-dose inhaled steroids, the Symbicort maintenance and reliever (SMART) regimen (with budesonide and formoterol fumarate), and anti-IgE therapy. Unlicensed treatments include methotrexate, azathioprine, ciclosporin, and subcutaneous terbutaline infusions. Paediatric data are needed on cytokine-specific monoclonal antibody therapies and bronchial thermoplasty. However, despite the interest in innovative approaches, getting the basics right in children with apparently severe asthma will remain the foundation of management for the foreseeable future.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Allergens; Anti-Asthmatic Agents; Asthma; Azathioprine; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Clinical Trials as Topic; Comorbidity; Cyclosporine; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Eosinophils; Ethanolamines; Formoterol Fumarate; House Calls; Humans; Immunoglobulin E; Interdisciplinary Communication; Methotrexate; Off-Label Use; Risk Factors; Severity of Illness Index; Spirometry; Terbutaline; Tobacco Smoke Pollution; Tomography, X-Ray Computed; Treatment Outcome

Formoterol is a long-acting beta(2)-agonist but because it has a fast onset of action it can also be used as a relief medication.. To asses the efficacy and safety of formoterol as reliever therapy in comparison to short-acting beta(2)-agonists in adults and children with asthma.. We searched the Cochrane Airways Group Specialised Register and websites of clinical trial registers (for unpublished trial data), and we checked the Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was February 2010.. Randomised, parallel-arm trials of at least 12 weeks duration in patients of any age and severity of asthma. Studies randomised patients to any dose of as-needed formoterol versus short-acting beta(2)-agonist. Concomitant use of inhaled corticosteroids or other maintenance medication was allowed, as long as this was not part of the randomised treatment regimen.. Two authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. We sought unpublished data on primary outcomes.. This review includes eight studies conducted in 22,604 participants (mostly adults). Six studies compared formoterol as-needed to terbutaline whilst two studies compared formoterol with salbutamol as-needed. Background maintenance therapy varied across the trials. Asthma exacerbations and serious adverse events showed a direction of treatment effect favouring formoterol, of which one outcome reached statistical significance (exacerbations requiring a course of oral corticosteroids). In patients on short-acting beta(2)-agonists, 117 people out of 1000 had exacerbations requiring oral corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for patients on formoterol as-needed. In patients on maintenance inhaled corticosteroids there were also significantly fewer exacerbations requiring a course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62 to 0.91). There was one death per 1000 people on formoterol or on short-acting beta(2)-agonists.. In adults, formoterol was similar to short-acting beta(2)-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta(2)-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta(2)-agonists should be given only to patients already taking inhaled corticosteroids.There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma.

Topics: Adult; Age Factors; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Cromolyn Sodium; Ethanolamines; Formoterol Fumarate; Humans; Nedocromil; Randomized Controlled Trials as Topic; Terbutaline

Budesonide and formoterol are available in a combined inhaler that offers therapeutic advantages in the treatment of asthma. The rapid onset of bronchodilation seen with formoterol means that budesonide/formoterol can be used as both maintenance and relief therapy. This approach has been shown to reduce exacerbations and overcome the problem of patients who overuse short-acting β-agonists at the expense of inhaled corticosteroids. Concerns regarding safety of long-acting β-agonists have not been confirmed in studies of the budesonide/formoterol combination inhaler, and we believe the benefits of this medication clearly outweigh any possible small increased risk.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Nebulizers and Vaporizers; Risk Assessment; Treatment Outcome

Formoterol has a fast onset of action and can therefore be used to relieve symptoms of asthma. A combination inhaler can deliver formoterol with different doses of inhaled corticosteroid; when used as a reliever both drugs will be delivered more frequently when asthma symptoms increase. This has the potential to treat both bronchoconstriction and inflammation in the early stages of exacerbations.. To assess the efficacy and safety of combined inhalers containing both formoterol and an inhaled corticosteroid when used for reliever therapy in adults and children with chronic asthma.. We last searched the Cochrane Airways Group trials register in April 2008.. Randomised trials in adults and children with chronic asthma, where a combination inhaler containing formoterol and inhaled corticosteroid is compared with fast-acting beta2-agonist alone for the relief of asthma symptoms. This should be the only planned difference between the trial arms.. Two review authors independently extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes.. Three trials involving 5905 participants were included. In patients with mild asthma who do not need maintenance treatment, no clinically important advantages of budesonide/formoterol as reliever were found in comparison to formoterol as reliever.Two studies enrolled patients with more severe asthma who were not controlled on high doses of inhaled corticosteroids (around 700 mcg/day in adults), and had suffered a clinically important asthma exacerbation in the past year. Hospitalisations related to asthma in the two studies comparing budesonide/formoterol for maintenance and relief with the same dose of budesonide/formoterol for maintenance with terbutaline for relief yielded an odds ratio of 0.68 (95% CI 0.40 to 1.16), which was not a statistically significant reduction. One adult study found a reduction in exacerbations requiring oral corticosteroids compared to terbutaline, odds ratio 0.56 (95% CI 0.42 to 0.74) and the study in children found less serious adverse events with budesonide/formoterol used for maintenance and relief. There was no significant difference in annual growth in children using budesonide/formoterol reliever in comparison to terbutaline.. In mild asthma it is not yet known whether patients who use a budesonide/formoterol inhaler for relief of asthma symptoms derive any clinically important benefits. In more severe asthma, one study that enrolled patients who were not controlled on quite high doses of inhaled corticosteroids, and had suffered an exacerbation in the previous year, demonstrated a reduction in the risk of exacerbations that require oral corticosteroids with budesonide/formoterol for maintenance and relief in comparison with budesonide/formoterol for maintenance and terbutaline or formoterol for relief. The incidence of serious adverse events in children was also less using budesonide/formoterol for maintenance and relief in one study, which similarly enrolled children who were not controlled on medium to high doses of inhaled corticosteroids, and compared to terbutaline relief with an explorative maintenance dose of budesonide/formoterol that is not approved for treatment.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchial Diseases; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Constriction, Pathologic; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Terbutaline

To compare the efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing or asthma.. Randomized, prospective, controlled trials published January 1996 to March 2008 with a minimum of 4 weeks of inhaled corticosteroids versus placebo were retrieved through Medline, Embase, and Central databases. The primary outcome was wheezing/asthma exacerbations; secondary outcomes were withdrawal caused by wheezing/asthma exacerbations, changes in symptoms score, pulmonary function (peak expiratory flow and forced expiratory volume in 1 second), or albuterol use.. Of eighty-nine studies identified, 29 (N = 3592 subjects) met the criteria for inclusion. Patients who received inhaled corticosteroids had significantly less wheezing/asthma exacerbations than those on placebo (18.0% vs 32.1%); posthoc subgroup analysis suggests that this effect was higher in those with a diagnosis of asthma than wheeze but was independent of age (infants versus preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler versus fluticasone metered-dose inhaler), mode of delivery (metered-dose inhaler versus nebulizer), and study quality (Jadad score: <4 vs >/=4) and duration (<12 vs >/=12 weeks). In addition, children treated with inhaled corticosteroids had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less albuterol use, and more clinical and functional improvement than those on placebo.. Infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations and improve their symptoms and lung function during treatment with inhaled corticosteroids.

Topics: Adrenal Cortex Hormones; Androstadienes; Asthma; Beclomethasone; Budesonide; Child, Preschool; Fluticasone; Humans; Infant; Lung Volume Measurements; Metered Dose Inhalers; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Respiratory Sounds; Secondary Prevention

Traditionally inhaled treatment for asthma has been considered as preventer and reliever therapy. The combination of formoterol and budesonide in a single inhaler introduces the possibility of using a single inhaler for both prevention and relief of symptoms (single inhaler therapy).. The aim of this review is to compare formoterol and corticosteroid in single inhaler for maintenance and relief of symptoms with inhaled corticosteroids for maintenance and a separate reliever inhaler.. We last searched the Cochrane Airways Group trials register in September 2008.. Randomised controlled trials in adults and children with chronic asthma.. Two review authors independently assessed studies for inclusion and extracted the characteristics and results of each study. Authors or manufacturers were asked to supply unpublished data in relation to primary outcomes.. Five studies on 5,378 adults compared single inhaler therapy with current best practice, and did not show a significant reduction in participants with exacerbations causing hospitalisation (Peto OR 0.59; 95% CI 0.24 to 1.45) or treated with oral steroids (OR 0.83; 95% CI 0.66 to 1.03). Three of these studies on 4281 adults did not show a significant reduction in time to first severe exacerbation needing medical intervention (HR 0.96; 95% CI 0.85 to 1.07). These trials demonstrated a reduction in the mean total daily dose of inhaled corticosteroids with single inhaler therapy (mean reduction ranged from 107 to 267 micrograms/day, but the trial results were not combined due to heterogeneity). The full results from four further studies on 4,600 adults comparing single inhaler therapy with current best practice are awaited.Three studies including 4,209 adults compared single inhaler therapy with higher dose budesonide maintenance and terbutaline for symptom relief. No significant reduction was found with single inhaler therapy in the risk of patients suffering an asthma exacerbation leading to hospitalisation (Peto OR 0.56; 95% CI 0.28 to 1.09), but fewer patients on single inhaler therapy needed a course of oral corticosteroids (OR 0.54; 95% CI 0.45 to 0.64). These results translate into an eleven month number needed to treat of 14 (95% CI 12 to 18), to prevent one patient being treated with oral corticosteroids for an exacerbation. The run-in for these studies involved withdrawal of long-acting beta(2)-agonists, and patients were recruited who were symptomatic during run-in.One study included children (N = 224), in which single inhaler therapy was compared to higher dose budesonide. There was a significant reduction in participants who needed an increase in their inhaled steroids with single inhaler therapy, but there were only two hospitalisations for asthma and no separate data on courses of oral corticosteroids. Less inhaled and oral corticosteroids were used in the single inhaler therapy group and the annual height gain was also 1 cm greater in the single inhaler therapy group, [95% CI 0.3 to 1.7 cm].There was no significant difference found in fatal or non-fatal serious adverse events for any of the comparisons.. Single inhaler therapy can reduce the risk of asthma exacerbations needing oral corticosteroids in comparison with fixed dose maintenance inhaled corticosteroids. Guidelines and common best practice suggest the addition of regular long-acting beta(2)-agonist to inhaled corticosteroids for uncontrolled asthma, and single inhaler therapy has not been demonstrated to significantly reduce exacerbations in comparison with current best practice, although results of five large trials are awaiting full publication. Single inhaler therapy is not currently licensed for children under 18 years of age in the United Kingdom.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Terbutaline

Although much progress has been achieved in the treatment of asthma it continues to constitute an important public health problem. Asthma guidelines have been developed to standardize the diagnosis and treatment of asthma worldwide. Studies on asthma control have unfortunately shown that asthma treatment is far from reaching the guideline goals. Recently the Symbicort Maintenance and Reliever Therapy (SMART) approach has gained importance in the control of asthma which suggests the use of a maintenance dose of budesonide/formoterol as well as budesonide/formoterol for relief. Several clinical studies evaluating the new approach have been completed. Use of budesonide/formoterol maintenance + reliever therapy led to a greater reduction in risks of exacerbations than the conventional treatment regimens (higher ICS or similar or higher ICS/LABA) with short-acting Beta(2)-agonist and provided similar or better current asthma control compared to high dose ICS/long acting Beta(2)-agonist therapy in moderate-severe, uncontrolled, persistent asthma patients. SMART studies also demonstrated that this approach is advantageous in terms of patient compliance since it allows the use of a single inhalation device as both maintenance and rescue therapy; led to lower total healthcare costs and did not differ from the conventional treatment regimens in terms of frequency of side effects. In all the above mentioned studies, mean ICS doses were found to be lower in budesonide/ formoterol maintenance and reliever therapy groups than in the comparison groups. Most studies have revealed better asthma control, improved respiratory function tests and reduced oral steroid use at lower ICS doses. SMART approach seems to be promising as a treatment approach that treats both chronic and dynamic increases in inflammation with maintenance and reliever therapy in uncontrolled, moderate-severe persistent asthma patients.

Topics: Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Ethanolamines; Formoterol Fumarate; Humans

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Middle Aged; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

The combination of inhaled corticosteroids (ICS) and long-acting beta2 agonists (LABA) has been used as a single inhaler both for maintenance and reliever therapy in asthma, the SMART approach. The administration of additional CS with each reliever inhalation in response to symptoms is expected to provide better control of airway inflammation. The aim of this meta-analysis was to evaluate the efficacy and safety of the SMART approach versus other approaches in the management of asthma in preventing asthma exacerbations.. We searched the MEDLINE and EMBASE databases for studies that have reported exacerbations in the SMART group versus the control group. We calculated the odds ratio (OR) and 95% confidence intervals (CI) to assess the exacerbations in the two groups and pooled the results using a random-effects model.. Our search yielded eight studies. The use of SMART approach compared to fixed-dose ICS-LABA combination significantly decreased the odds of a severe exacerbation (OR 0.65; 95% CI, 0.53-0.80) and severe exacerbation requiring hospitalization/ER treatment (OR 0.69; 95% CI, 058-0.83). The use of SMART approach compared to fixed-dose ICS also significantly decreased the odds of a severe exacerbation (OR 0.52; 95% CI, 0.45-0.61) and severe exacerbation requiring medical intervention (OR 0.52; 95% CI, 0.42-0.65). The occurrence of adverse events was similar in the two groups. There was some evidence of statistical heterogeneity.. The SMART approach using formoterol-budesonide is superior in preventing exacerbations when compared to traditional therapy with fixed dose ICS or ICS-LABA combination without any increase in adverse events.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Disease Progression; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Humans; Odds Ratio

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Fluticasone; Glucocorticoids; Humans; Japan; Pediatrics; Practice Guidelines as Topic; Severity of Illness Index

Combination therapies are frequently recommended as maintenance therapy for people with asthma, whose disease is not adequately controlled with inhaled steroids. Fluticasone/salmeterol (FP/SAL) and budesonide/formoterol (BUD/F) have been assessed against their respective monocomponents, but there is a need to compare these two therapies on a head-to-head basis.. To estimate the relative effects of fluticasone/salmeterol and budesonide/formoterol in terms of asthma control, safety and lung function.. We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Searches are current to May 2008.. Randomised studies comparing fixed dose FP/SAL and BUD/F were eligible, for a minimum of 12 weeks. Crossover studies were excluded. Our primary outcomes were: i) exacerbations requiring oral steroid bursts, ii) hospital admission and iii) serious adverse events.. Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR).. Five studies met the review entry criteria (5537 participants).. The odds of an exacerbation requiring oral steroids did not differ significantly between treatments (OR 0.89; 95% CI 0.73 to 1.09, three studies, 4515 participants). The odds of an exacerbation leading hospital admission were also not significantly different (OR 1.29; 95% CI 0.68 to 2.47, four studies, 4879 participants). The odds of serious adverse events did not differ significantly between treatments (OR 1.47; 95% CI 0.75, 2.86, three studies, 4054 participants).. Lung function outcomes, symptoms, rescue medication, exacerbations leading ED visit/hospital admission and adverse events were not significantly different between treatments.. The evidence in this review indicates that differences in the requirement for oral steroids and hospital admission between BUD/F and FP/SAL do not reach statistical significance. However, the confidence intervals do not exclude clinically important differences between treatments in reducing exacerbations or causing adverse events. The width of the confidence intervals for the primary outcomes justify further trials in order to better determine the relative effects of these drug combinations. Although this review sought to assess the effects of these drugs in both adults and children, no trials were identified in the under-12s and research in this area is of a high priority.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

*The corticosteroid budesonide and the long-acting [beta]2-adrenoceptor agonist formoterol have been combined into a single pressurized metered-dose inhaler (pMDI) for use in patients aged > or =12 years with asthma. *In well designed 12-week clinical trials in patients with mild to moderate or moderate to severe persistent asthma, lung function improved to a significantly greater extent with twice-daily budesonide/formoterol pMDI 160 [micro]g/9 [micro]g or 320 [micro]g/9 [micro]g than with placebo or the same nominal dosage of either of the components alone. *Budesonide/formoterol pMDI was also associated with improvements from baseline in patient-reported asthma control, asthma symptom and asthma-related quality of life outcomes that were significantly greater than those with placebo and, for many endpoints, monotherapy with the individual components. *In a 52-week safety study, treatment with twice-daily budesonide/formoterol pMDI 320 [micro]g/9 [micro]g was associated with rapid and durable improvements in lung function and asthma control that were significantly greater than those with twice-daily budesonide pMDI 640 [micro]g monotherapy. *Budesonide/formoterol pMDI was well tolerated in clinical trials. Its overall adverse event profile is consistent with the known tolerability profiles of long-acting [beta]2-adrenoceptor agonist and inhaled corticosteroid therapy, and is similar to that shown with placebo.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Treatment Outcome

Inhaled corticosteroid (ICS) therapy is central to the long-term management of asthma and is extensively used in the management of chronic obstructive pulmonary disease (COPD). While administration via inhalation limits systemic exposure compared with oral or injected corticosteroids and, therefore, the risk of systemic corticosteroid-related adverse effects, concerns over the long-term safety of ICS persist. The assessment of the long-term effects of ICS therapy requires considerable research effort over years or even decades. Surrogate markers/predictors for clinical endpoints such as adrenal crisis, reduced final height and fractures have been identified for use in relatively short-term studies. However, the predictive value of such markers remains questionable.Inhaled budesonide has been available since the early 1980s and there is a considerable evidence base investigating the safety of this agent. To assess the long-term safety of inhaled budesonide therapy in terms of the actual incidence of the clinical endpoints adrenal crisis/insufficiency, reduced final height, fractures and pregnancy complications, we undertook a review of the scientific literature. The external databases BIOSIS, Cochrane Central Register of Controlled Trials, Current Contents, EMBASE, International Pharmaceutical Abstracts and MEDLINE were searched, in addition to AstraZeneca's internal product literature database Planet, up to 29 February 2008. Only original articles of epidemiological studies, national surveys, clinical trials and case reports concerning inhaled budesonide were included.Eight surveys of adrenal crisis were found. The only survey with specified criteria for diagnosis involved 2912 paediatricians and endocrinologists and revealed 33 patients with adrenal crisis associated with ICS therapy; only one patient used budesonide (in co-treatment with fluticasone propionate). In addition, 14 case reports of adrenal crisis in budesonide-treated patients were found. In only two of these, budesonide was used at recommended doses and in the absence of interacting medication.Three retrospective studies and one prospective study assessing final height were found. None of them showed any reduced final height in patients receiving inhaled budesonide during childhood or adolescence.Seventeen epidemiological studies investigating the risk of fractures were found. When adjusting for confounding factors, they did not provide any unequivocal data for an increased fracture risk wi

Topics: Administration, Inhalation; Adrenal Gland Diseases; Adult; Asthma; Body Height; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Female; Fractures, Bone; Humans; Pregnancy; Young Adult

The Global Initiative for Asthma (GINA) guidelines aim at improving asthma control and preventing future risk. For patients with moderate to severe asthma an inhaled corticosteroid (ICS) or an ICS/long-acting beta2-agonist (LABA) combination with a short-acting beta2-agonist (SABA) as reliever is recommended. Despite the availability of effective maintenance therapies, a large proportion of patients still fail to achieve guideline-defined asthma control, and overuse of SABA reliever medication at the expense of ICS is commonly observed. New simplified treatment approaches may offer a solution and assist physicians to achieve overall asthma control. One such treatment approach, which is recommended in the GINA guidelines, is budesonide/formoterol for both maintenance and reliever therapy. This treatment strategy significantly reduces the rate of severe asthma exacerbations compared with ICS/LABA plus SABA and achieves equivalent daily symptom control compared with higher doses of ICS/LABA plus separate SABA for relief. These benefits are achieved at a lower overall steroid load, and budesonide/formoterol maintenance and reliever therapy is well tolerated in patients with moderate to severe asthma. This review discusses current asthma management in patients with moderate to severe disease and examines the evidence for alternative asthma management approaches.

Topics: Administration, Inhalation; Animals; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Severity of Illness Index

Although the available inhaled corticosteroid (ICS)/long-acting beta( 2)-agonist (LABA) combinations principally work in a similar fashion, they differ in several important ways, leading to different efficacy. The ICS/LABA combination product budesonide/formoterol can be used as both maintenance and reliever therapy, providing a fixed maintenance dose, which does not change, and replacing short-acting beta(2)-agonists as relievers thereby allowing intervention to address the underlying inflammation at the earliest sign of symptomatic worsening. This approach is not suitable for other combination products such as salmeterol/fluticasone. Here we review the pharmacological differences of budesonide/ formoterol and salmeterol/fluticasone that permit the use of budesonide/formoterol as both maintenance and reliever therapy.

Topics: Adrenergic beta-Agonists; Albuterol; Anti-Inflammatory Agents; Asthma; Budesonide; Disease Progression; Drug Therapy, Combination; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

This systematic review examines the published evidence on the pharmacoecomonics of Symbicort. Symbicort is a combination inhaler used in asthma and chronic obstructive pulmonary disease (COPD) that contains budesonide and formoterol. In asthma, Symbicort can be used as fixed or adjustable dose maintenance therapy as well as for both maintenance and reliever therapy (SMART).. A literature search of PubMed was carried out to find all publications on the pharmacoeconomics of Symbicort. Additional studies were searched for in the reference lists of the papers retrieved and by searching tables of contents of relevant journals. A total of 13 studies on Symbicort in asthma and 2 studies on Symbicort in COPD were found.. Total costs were lower with Symbicort than with separate inhalers containing budesonide and formoterol. Adjustable dosing maintained control of asthma using less medication and was associated with lower treatment costs than fixed dosing with Symbicort or the combination of fluticasone/salmeterol. SMART improves asthma control, reduces exacerbations and reduces direct and indirect costs compared to fixed maintenance therapy with either Symbicort or fluticasone/salmeterol. In COPD, Symbicort offers clinical advantages over therapy with the monocomponents and these are achieved at little or no extra cost.

Topics: Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Economics, Pharmaceutical; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Pulmonary Disease, Chronic Obstructive

Asthma is characterised by variable airflow obstruction, airway inflammation and hyper-responsiveness. Persistent inflammation is thought to lead to 'remodelling' of the airway, which in turn leads to the progressive loss of lung function seen in asthmatics. It would appear logical that anti-inflammatory drugs such as inhaled corticosteroids (ICS) would influence the natural history of asthma by reducing inflammation, subsequent remodelling, and thus preventing the decline in lung function. This review will summarise the effects of ICS on the secondary prevention of asthma, lung function and remodelling.. Many published studies show a reduction in airway inflammation, improvement in clinical symptoms and prebronchodilator lung function whilst taking ICS. Few studies, however, examine their effect on the natural history of asthma. Several recent studies have targeted very young children with asthma using ICS, and despite their differing target populations and treatment strategies, have failed to show any difference in lung function. Studies in adults with mild persistent asthma show similar findings. ICS appear to reverse some of the processes involved in airway remodelling, but not all.. Although ICS are effective in controlling symptoms they do not appear to alter the natural history of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Age Factors; Airway Obstruction; Asthma; Budesonide; Child; Humans; Infant; Respiratory Physiological Phenomena

The connection between asthma and rhinitis is not a new discovery. Significant progress has been made in understanding the relationship of these two conditions, however, and the implications of the asthma-rhinitis link make it increasingly important. Patients who have asthma and rhinitis tend to have more severe disease with higher treatment costs. Treatment of rhinitis may improve asthma control, and early treatment of allergies may prevent the development of asthma. This article more fully explores the epidemiologic, pathophysiologic, and clinical relationships between asthma and rhinitis.

Topics: Anti-Inflammatory Agents; Asthma; Budesonide; Comorbidity; Humans; Immunotherapy; Intercellular Adhesion Molecule-1; Rhinitis, Allergic, Perennial; Vascular Cell Adhesion Molecule-1

Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects.. To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma.. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007.. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01).. The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

An inhaled corticosteroid (ICS) or an ICS/long-acting beta(2)-agonist (LABA) combination plus short-acting beta(2)-agonist (SABA) as needed for symptom relief is recommended for persistent asthma. Additionally, budesonide/formoterol maintenance and reliever therapy (Symbicort) SMART, AstraZeneca, Sweden) has been approved for adults in the European Union. This option is well tolerated and offers greater reductions in asthma exacerbations together with similar improvements in daily symptom control, at a lower overall steroid load, compared with fixed-dose ICS/LABA plus SABA.. Two large clinical trials investigated the use of budesonide/formoterol as maintenance and reliever compared with medium or high doses of an ICS/LABA combination as controller plus SABA as reliever in adults (aged >or= 18 years). COMPASS was a 6-month, double-blind, randomized trial, while COSMOS was a 1-year, dose titration study which reflected routine clinical practice.. Among adults, the studies confirmed a 21-39% reduction in severe exacerbations in patients treated with budesonide/formoterol maintenance and reliever therapy compared with titrated salmeterol/fluticasone plus SABA (COSMOS) or fixed higher budesonide/formoterol or salmeterol/fluticasone plus SABA (COMPASS), respectively. Similar levels of daily asthma control were achieved with budesonide/formoterol maintenance and reliever therapy at a significantly lower overall steroid load compared with salmeterol/fluticasone or budesonide/formoterol plus SABA. Budesonide/formoterol maintenance and reliever therapy was as well tolerated as combination therapies.. In adult patients, budesonide/formoterol maintenance and reliever therapy is a safe and simplified approach to asthma management, using a single inhaler, which reduces severe exacerbations and maintains similar daily asthma control at a lower drug load compared with the traditional strategy of ICS/LABA plus SABA.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Clinical Trials as Topic; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome

In the recent years, considerable insight has been gained in to the optimal management of adult asthma. Most adult patients with asthma have mild intermittent and persistent disease, and it is acknowledged that many patients do not reach full control of all symptoms and signs of asthma. Those with mild persistent asthma are usually not well controlled without inhaled corticosteroids (ICS). Studies have provided firm evidence that these patients can be well controlled when receiving ICS, especially when disease is of recent onset. This treatment should be given on a daily basis at a low dose and when providing a good response should be maintained to prevent severe exacerbations and disease deterioration. Intermittent ICS treatment at the time of an exacerbation has also been suggested as a strategy for mild persistent asthma, but it is less effective than low-dose regular treatment for most outcomes. Adding a long-acting beta-agonist (LABA) to ICS appears to be unnecessary in most of these patients for optimising control of their asthma. Patients with moderate persistent asthma can be regarded as those who are not ideally controlled on low-dose ICS alone. The combination of an ICS and LABA is preferred in these patients, irrespective of the brand of medicine, and this combination is better than doubling or even quadrupling the dose of ICS to achieve better asthma control and reduce exacerbation risks. An ICS/LABA combination in a single inhaler represents a safe, effective and convenient treatment option for the management of patients with asthma unstable on inhaled steroids alone. Ideally, once asthma is under full control, the dose of inhaled steroids should be reduced, which is possible in many patients. The duration of treatment before initiating this dose reduction has, however, not been fully established. One of the combinations available to treat asthma (budesonide and formoterol) has also been assessed as both maintenance and rescue therapy with a further reduction in the risk for a severe exacerbation. Clinical effectiveness in the real world now has to be established, since this approach likely improves compliance with regular maintenance therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Severity of Illness Index; Treatment Outcome

The use of systemic corticosteroids, together with bronchodilators and oxygen therapy, has become established for the management of acute asthma. These agents are undoubtedly effective, but are also associated with problems such as metabolic adverse effects. Inhaled corticosteroids (ICS) offer potential benefit in the acute setting because they are delivered directly to the airways. They are also likely to reduce systemic exposure, which would lead in turn to reductions in rates of unwanted systemic effects. In order to evaluate the role of budesonide in the management of acute asthma exacerbations we conducted a review of the literature and critically evaluated the rationale for the use of ICS in general in this setting. Trials in adults and children requiring treatment for acute exacerbation of asthma have shown clinical and/or spirometric benefit for budesonide when delivered via nebulizer, dry powder inhaler, or aerosol in the emergency department, hospital and follow-up settings. The efficacy seems to benefit from high doses given repeatedly during the initial phase of an acute exacerbation. These acute effects are likely to be linked to the drug's distinctive pharmacokinetic and pharmacodynamic profile. The current evidence base revealed encouraging results regarding the efficacy of the ICS budesonide in patients with wheeze and acute worsening of asthma. Future studies should focus on the efficacy of these agents in more severe asthma worsenings.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Administration Schedule; Emergencies; Glucocorticoids; Hospitalization; Humans; Respiratory Sounds; Treatment Outcome

Clinical trials have recently demonstrated that using a budesonide/formoterol combination inhaler as regular maintenance treatment twice daily but also as a rescue therapy for breakthrough symptoms can provide more effective control of asthma, particularly in reducing exacerbations, than using a short-acting beta2-agonist or formoterol as rescue therapy. This suggests that the corticosteroid component of the combination therapy plays an important role in rescue therapy. Formoterol as a rescue therapy is effective in relieving symptoms by relaxing airway smooth muscle but is also likely to have important inhibitory effects on mast cells, plasma exudation and neutrophilic inflammation. Inhaled corticosteroids have much more rapid suppressing effects on airway inflammation than previously recognised and the increased dose used as rescue therapy may prevent the increase in airway inflammation that occurs during the evolution of an exacerbation, thus preventing its development. It is likely that the molecular interactions between beta2-agonists and corticosteroids also enhance the effect of the combination therapy as rescue therapy. There is now a strong scientific rationale for single inhaler therapy in asthma, but more research is now needed to better understand the mechanisms involved.

Topics: Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchodilator Agents; Budesonide; Capillary Permeability; Delayed-Action Preparations; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Mast Cells; Muscle, Smooth; Nebulizers and Vaporizers; Neutrophils; Treatment Outcome

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Chemical Phenomena; Chemistry, Physical; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Esterification; Glucocorticoids; Humans; Respiratory System

In some patients, asthma control is improved by combining inhaled corticosteroids with long-acting beta(2)-agonists. However, fluctuating asthma control and exacerbations can still occur. The STAY study evaluated whether, in patients with moderate to severe asthma, replacing a short-acting beta(2)-agonist reliever with the combination of budesonide/formoterol as reliever would both provide rapid symptom relief and reduce asthma exacerbations. The study evaluated 2760 patients with asthma (4-80 years) randomized to budesonide 400 microg twice daily (bid) and terbutaline as reliever, budesonide/formoterol 100/6 microg bid and terbutaline as reliever, or budesonide/formoterol 100/6 microg bid both as maintenance and reliever. Children (age 4-11 years) used a once-daily maintenance dose. Budesonide/formoterol as maintenance and reliever significantly reduced severe exacerbation risk by 45% to 47% compared with the other 2 treatments and improved symptoms, awakenings, and lung function. The benefit was seen in patients of all ages. Subsequent studies have revealed that this beneficial effect of budesonide/formoterol as maintenance and reliever requires both components of the combination.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans

To compare the effectiveness of budesonide/formoterol using fixed dosing (BUD/FORM) with inhaled corticosteroid (ICS) alone or alternative ICS and long-acting beta(2)-agonist (LABA) regimens for adults with moderate/severe asthma.. BIOSIS, CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in July 2006. No restriction was placed on language. Meta-analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with BUD/FORM had an equivalent daily dose of ICS at the start of the trial. The primary outcome measure was, 'treatment failure', defined as: asthma-related serious adverse event, oral glucocorticosteroid treatment, A&E visit and/or admission to hospital, withdrawal due to a need for additional asthma therapy.. Of the 330 papers identified in the literature search, 15 met the inclusion criteria. The following alternative treatments were found: ICS alone (BUD), BUD/FORM adjustable maintenance dose (BUD/FORM-AMD), and salmeterol/fluticasone in a single inhaler (SALM/FP). Meta-analysis of treatment failure demonstrated a 50% increase with BUD versus BUD/FORM (Relative Risk [RR] 1.50, 95% confidence interval [95% CI]: 1.12-2.02, p = 0.007; 2 RCTs); a trend in favour of a reduction with BUD/FORM-AMD versus BUD/FORM (RR 0.88, 95% CI: 0.77-1.02, p = 0.09; 11 RCTs); and no evidence of a difference with SALM/FP versus BUD/FORM (RR 0.99, 95% CI: 0.83-1.16, p = 0.86; 3 RCTs). Significant heterogeneity was not detected in the primary analyses. Secondary analyses demonstrated the following significant differences: hospitalisations/A&E visits (49% increased risk with SALM/FP vs. BUD/FORM, RR 1.49, 95% CI: 1.07-2.08, p = 0.02, and 28% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.72, 95% CI: 0.52-0.99, p = 0.04); and use of oral steroids (51% increase in risk with BUD vs. BUD/FORM, RR 1.51, 95% CI: 1.10-2.09, p = 0.01, and 19% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.81, 95% CI: 0.70-0.95, p = 0.01).. Fixed-dose BUD/FORM is an effective treatment option for adult patients with moderate/severe asthma when compared to BUD and SALM/FP, with adjustable maintenance dosing demonstrating important advantages over fixed dosing in relation to exacerbation prevention and reduced treatment load.

Topics: Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Practice Guidelines as Topic; Publication Bias; Treatment Outcome

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Professional Practice; Salvage Therapy

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2007) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2006).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. Seventy-one studies (14,602 participants) representing 74 randomised comparisons met the inclusion criteria. Methodological quality was fair. Dose ratio 1:2: FP produced a significantly greater end of treatment FEV1 (0.04 litres (95% CI 0 to 0.07 litres), end of treatment and change in morning PEF, but not change in FEV1 or evening PEF. This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. FP led to fewer symptoms and less rescue medication use. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in morning PEF, evening PEF, and FEV1 over BDP or BUD. The effects on exacerbations were mixed. There were no significant differences incidence of hoarseness, pharyngitis, candidiasis, or cough.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

The use of combination budesonide/formoterol dry powder inhaler (Symbicort Turbuhaler) for both daily maintenance therapy and as-needed relief of breakthrough symptoms using a single inhaler is a new approach to asthma management that is indicated in patients with persistent asthma not adequately controlled by conventional regimens using reliever therapy with a short-acting beta(2)-adrenoceptor agonist alone. The administration of additional corticosteroid with each reliever inhalation in response to symptoms is expected to provide improved control of airway inflammation.Budesonide/formoterol maintenance and reliever therapy reduced the risk of severe asthma exacerbations compared with conventional regimens using a short-acting beta(2)-adrenoceptor agonist alone as reliever therapy in the majority of trials, while providing similar or better daily asthma control than higher fixed maintenance doses of budesonide or inhaled corticosteroid/long-acting beta(2)-adrenoceptor agonist combination therapy in patients with generally moderate to severe, uncontrolled, persistent asthma. The strategy offers the convenience of a single inhaler and simplifies treatment by providing immediate additional anti-inflammatory medication in response to asthma symptoms and immediate step-down when symptoms abate. The improved efficacy, with respect to exacerbation prevention, observed with budesonide/formoterol maintenance and reliever therapy in all double-blind comparative trials was achieved with a lower mean daily dose of inhaled corticosteroid or with fewer daily inhalations of reliever medication. Budesonide/formoterol maintenance and reliever therapy was well tolerated with an incidence of adverse events similar to that with conventional regimens. Therefore, it offers a new approach to therapy in patients with uncontrolled, persistent asthma; providing improved efficacy with a lower overall drug load.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers

New evidence has suggested that people with asthma who are homozygous for arginine at aminoacid 16 of the beta2-adrenergic receptor (ADRB2) might not benefit from longacting beta2-agonist therapy. We, therefore, investigated whether ADRB2 polymorphisms affect response to longacting beta2-agonists in combination with inhaled corticosteroids.. Asthmatics were stratified by ADRB2 genotype in two studies to assess the effects of inhaled corticosteroids plus longacting beta2-agonists on asthma exacerbations. In study 1 (double-blind), 2250 asthmatics were randomly assigned to budesonide plus formoterol maintenance and reliever therapy, fixed-dose budesonide plus formoterol, or fixed-dose fluticasone plus salmeterol for 6 months. Study 2 (open-label) consisted of 405 asthmatics and compared an adjustable regimen of budesonide plus formoterol with fixed-dose budesonide plus formoterol and fixed-dose fluticasone plus salmeterol for 7 months. The relation between ADRB2 polymorphism, severe asthma exacerbations, and other asthma outcomes was analysed. Primary endpoints for studies 1 and 2 were severe asthma exacerbation and asthma control as assessed by measures of exacerbations, respectively.. In study 1, Gly16Arg genotype had no effect on the percentage of participants with severe exacerbations across all treatment groups (99 [12%] of 833 Gly/Gly, 110 [11%] of 1028 Gly/Arg, and 32 [9%] of 361 Arg/Arg participants). Secondary endpoints, including forced expiratory volume in 1 s, peak expiratory flow, use of as-needed medication, and number of nights with awakenings were similar between genotype groups. No relation was recorded between ADRB2 haplotype and primary and secondary endpoints. In study 2, the frequency of asthma exacerbations (15 [9%] of 168 Gly/Gly, 13 [8%] of 169 Gly/Arg, and 6 [9%] of 67 Arg/Arg participants) and other study endpoints were closely similar for all ADRB2 genotypes.. Since we showed no pharmacogenetic effect of ADRB2 variation on therapeutic response in asthma, patients, irrespective of their genotype, can continue to receive inhaled corticosteroids plus longacting beta2-agonists.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Budesonide; Ethanolamines; Female; Formoterol Fumarate; Genotype; Humans; Male; Peak Expiratory Flow Rate; Pharmacogenetics; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate

Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear.. To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999). Date of last search August 2005.. Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1.. Two studies were selected for inclusion (63 subjects), both concerned adults. An additional small study including 14 children was identified for the 2005 update. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery.. Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that still require further assessment. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Delivery Systems; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor agonists is increasingly used as maintenance therapy in patients with moderate to severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of inhaled corticosteroids is thought to be mediated through suppression of airway inflammation, while long-acting beta2-adrenoceptor agonists are thought to work by inducing bronchodilation. However, there is emerging data to indicate that these two classes of drugs interact positively with each other, leading to added or perhaps synergistic benefits for patients. Corticosteroids enhance the expression of beta2-adrenoceptor, thus providing protection against desensitization and development of tolerance to beta2-adrenoceptor agonists, which may occur with prolonged use of these medications. Long-acting beta2-adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory effects of corticosteroids by accelerating nuclear translocation of the glucocorticoid receptor complex, and enhancing transcription and expression of steroid-inducible genes in pro-inflammatory cells. In clinical trials, corticosteroids in combination with long-acting beta2-adrenoceptor agonists reduce exacerbation rates, and improve lung function and health status of patients with moderate to severe asthma or COPD beyond that achieved by individual component therapy. Their effects on mortality are unknown. There is a large clinical trial currently underway, which will provide mortality data by the year 2006. On balance, clinical evidence supports the use of combination therapy in moderate to severe asthma and COPD.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Gene Expression Regulation; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Receptors, Glucocorticoid

Randomised, double-blind studies with a knemometer have shown that the risk of inhaled glucocorticoid-induced growth suppression depends on dose, administration regimen, delivery device and specific glucocorticoid. Dry-powder beclomethasone dipropionate, 300-400 microg daily, and budesonide, 400 microg daily, suppress height growth rate by 20-25% during the first year of treatment, whereas lower doses of budesonide and fluticasone propionate do not affect growth rate. Available assessments of final height are flawed by poor compliance rates. Children with asthma on continuous treatment with inhaled glucocorticoids should have their height measured at six-month intervals. In the case of growth deviation, they should be referred for evaluation.

Topics: Administration, Inhalation; Anthropometry; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Glucocorticoids; Growth; Humans; Leg; Randomized Controlled Trials as Topic

Therapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers. A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews. Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramycin, or colistin are physico-chemically compatible. Physico-chemical compatibility has been demonstrated for admixtures of cromolyn with albuterol and/or ipratropium and for admixtures of cromolyn and budesonide. Admixtures of budesonide with ipratropium and/or fenoterol, and admixtures of budesonide and albuterol, or cromolyn are physico-chemically compatible. Both cromolyn and colistin are incompatible with benzalkonium chloride. Admixtures should be prepared from inhalation solutions/suspensions formulated without preservatives. Besides studies of the physico-chemical compatibility, the aerodynamic behaviour of physico-chemical mixtures needs to be studied before a final recommendation of simultaneous nebulization of compatible admixtures can be made.

Topics: Acetylcysteine; Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Budesonide; Colistin; Cromolyn Sodium; Cystic Fibrosis; Deoxyribonuclease I; Drug Therapy, Combination; Expectorants; Humans; Ipratropium; Nebulizers and Vaporizers; Respiratory Therapy; Tobramycin

Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma.. We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer.. Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response.. There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids form the cornerstone of treatment for most patients with asthma. A range of compounds are available with a wide range of prescribable doses. In this overview, we summarize the findings from a number of Cochrane systematic reviews that have examined the relative benefits of different doses of beclometasone dipropionate, budesonide and fluticasone propionate when used to treat children and adults. The key findings are that all inhaled corticosteroids demonstrate a dose-response relationship for efficacy measures, but most of the benefit in mild-to-moderate severity disease is gained in the low-to-moderate dose range of each drug. In this group, high doses of fluticasone lead to small improvements in measures of control at the expense of a steep increase in the incidence of oral side-effects. In patients with severe disease who are dependent on oral steroids, there may be appreciable benefit in reducing oral steroids from very high compared with high doses of fluticasone.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Evidence-Based Medicine; Fluticasone; Forced Expiratory Volume; Humans; Peak Expiratory Flow Rate; Treatment Outcome

To discuss the clinical efficacy and safety of formoterol when used to relieve symptoms of asthma and prevent exercise-induced bronchoconstriction (EIB).. A PubMed search was performed for articles published between 1997 and 2005 with the keywords formoterol, asthma, and long-acting beta2-adrenergic agonist, with cross-referencing to identify peer-reviewed journal articles.. Published articles on the clinical use of formoterol for asthma or EIB were included as well as articles detailing the pharmacologic properties of the drug. To present a thorough review of the literature, published studies based on patient number, study design, or other measures of study quality were not excluded.. Formoterol is the only long-acting beta2-adrenergic agonist that combines a rapid onset of action (within 3 minutes) with a long duration of effect (approximately 12 hours). Clinically, as recommended by asthma treatment guidelines, formoterol in conjunction with inhaled corticosteroids (ICSs) is a preferred treatment for moderate to severe persistent asthma. Significant clinical data support the use of formoterol in combination with ICSs for the treatment of asthma, with studies demonstrating improved pulmonary function and symptom scores and decreased need for maintenance ICSs and short-acting beta2-adrenergic agonists (SABAs) as relief medication. Recent studies also demonstrate that use of formoterol as needed as relief medication is associated with a prolonged time to exacerbation, improved pulmonary function, and decreased asthma symptoms. When used as monotherapy, formoterol provides protection against EIB. Clinical data also demonstrate that formoterol is safe and well tolerated even in high doses, with an adverse event profile similar to that of SABAs.. Overall, formoterol is safe and effective as adjunct controller therapy for moderate and severe persistent asthma and as monotherapy for EIB.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Hydrophobic and Hydrophilic Interactions; Hypokalemia; Infant; Polymorphism, Genetic; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Tachycardia; Terbutaline; Treatment Outcome

Patients with mild persistent asthma rarely see their doctor with symptoms of the disease. Partly as a result of this situation, mild asthma is generally undertreated. Findings of several large randomised clinical trials have shown benefits for this population of regular treatment with low doses of inhaled corticosteroids. Additional drugs are rarely needed, and although leukotriene modifiers are effective, they are less so than inhaled corticosteroids. People with moderate persistent asthma are not well controlled on low doses of inhaled corticosteroids. A combination of this drug and long-acting inhaled beta2 agonists provides improved control compared with doubling of the maintenance dose of inhaled corticosteroids. The combination of budesonide and formoterol has been assessed as both maintenance and reliever treatment. This approach further reduces the risk for severe exacerbations. With these strategies, most individuals can achieve good control of their asthma. For patients who do not achieve asthma control despite taking drugs, measurement of the inflammatory response in the airway in induced sputum could provide further information to guide treatment.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Severity of Illness Index

Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting beta(2)-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment of the cost effectiveness of ICS plus LABA combination therapy for asthma. A systematic literature research was conducted in MEDLINE to identify studies published between January 1994 and September 2005. Cost-effectiveness studies derived from 11 clinical studies were identified. The ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus a leukotriene antagonist in two studies, and a leukotriene antagonist alone in one study. All studies focused on measuring direct medical costs in a total of six different healthcare systems, and three studies conducted sensitivity analyses, including productivity costs. Outcomes were measured in treatment success (changes in lung function), episode-free days, and symptom-free days by evaluating short-term follow-up. The combination of ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Further considerations for measuring long-term outcomes and dose-response relationships might be required to provide further evidence on the cost effectiveness of combination therapy with ICS plus LABA.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Clinical Trials as Topic; Cost-Benefit Analysis; Cyclopropanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Quinolines; Sulfides

Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma.. Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected.. In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate.. ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Bone and Bones; Bone Density; Budesonide; Child; Child Development; Fluticasone; Humans; Pregnenediones; Treatment Outcome

Asthma is the most common chronic illness among children, and inhaled corticosteroids (ICS) are the most effective long-term therapy available for suppressing airway inflammation in persistent asthma. While the primary aim of ICS therapy is good efficacy with minimal side effects, early diagnosis and treatment of asthma can also improve asthma control and normalize lung function, and may prevent irreversible airway injury. Poor patient compliance is a major barrier to treatment. Simplified dosing regimens (e.g., once-daily administration), good inhaler technique, and education of the patient/caregiver should improve patient compliance. Concerns over ICS therapy are often based on the potential for systemic effects associated with oral corticosteroids (e.g., effects on bone mineral density, or growth suppression in children). Since adverse events are associated with high doses of ICS, the dose in all patients should be titrated to the minimum effective dose required to maintain control. Optimal distribution of an ICS in the lungs rather than the systemic compartment is affected by several factors, including the drug's pharmacokinetic profile, inhaler type, inhaler technique, and drug particle size. For young patients unable to use a dry-powder inhaler or pressurized metered-dose inhaler, a nebulizer facilitates drug delivery through passive inhalation; ICS therapy in the form of budesonide inhalation suspension can be given to children with persistent asthma from 12 months of age. In conclusion, selecting a drug with good efficacy and minimal side effects, such as budesonide, together with an easy-to-use delivery system and ongoing patient/caregiver education, is important in optimizing ICS therapy for children with persistent asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Chronic Disease; Drug Administration Schedule; Female; Humans; Infant; Male; Patient Compliance; Patient Education as Topic; Safety

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2004) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. Fifty six studies (12, 119 participants) met the inclusion criteria. Methodological quality was variable. Dose ratio 1:2: FP produced a significantly greater FEV1 (0.14 litres, 95% Confidence Interval (CI) 0.06 to 0.22), morning PEF (11.10 L/min, 95%CI 3.12 to 19.09 L/min) and evening PEF (9.31 L/min, 95%CI 5.12 to 13.5 L/min). This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in am PEF (9.58 L/min (95% CI 5.20 to 13.97)), pm PEF (7.41 L/min (95% CI 2.61 to 12.22)), and FEV1 (0.09 L (0.02 to 0.17)). The effects on exacerbations were mixed. There was an increase in the incidence of hoarseness, but no significant difference in pharyngitis, candidiasis, or cough.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing hoarseness when given at the same daily dose. Future studies should attempt to establish the relative efficacy of inhaled steroids delivered with CFC-free propellants.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICSs) have become the mainstay of chronic controller therapy to treat airways inflammation in asthma and to reduce exacerbations in chronic obstructive pulmonary disease. An array of ICSs are now available that are aerosolized by a range of delivery systems. Such devices include pressurized (or propellant) metered-dose inhalers (pMDIs), pMDIs plus valved holding chambers or spacers, breath-actuated inhalers, and nebulizers. More recently, dry-powder inhalers (DPIs) were developed to help overcome problems of hand-breath coordination associated with pMDIs. The clinical benefit of ICSs therapy is determined by a complex interplay between the nature and severity of the disease, the type of drug and its formulation, and characteristics of the delivery device together with the patient's ability to use the device correctly. The ICSs budesonide is available by pMDI, DPI, and nebulizer-allowing the physician to select the best device for each individual patient. Indeed, the availability of budesonide in three different delivery systems allows versatility for the prescribing physician and provides continuity of drug therapy for younger patients who may remain on the same ICSs as they mature.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Choice Behavior; Dose-Response Relationship, Drug; Equipment Design; Female; Humans; Long-Term Care; Male; Metered Dose Inhalers; Particle Size; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Treatment Outcome

Inadequately controlled rhinitis is associated with worsening asthma, one of the most common potentially serious causes of pregnancy complications. Recent evidence-based guidelines now stress the importance of inhaled corticosteroids as first-line therapy in controlling asthma during pregnancy, with preference given to budesonide. Both inhaled and intranasal budesonide formulations are rated Pregnancy Category B; all other inhaled and intranasal corticosteroids are rated Pregnancy Category C.. To review data from clinical and epidemiological studies investigating the effects of orally inhaled or intranasal budesonide on pregnancy outcomes.. Clinical and epidemiological studies on the effects of maternal exposure to orally inhaled or intranasal budesonide were identified through searches of the literature indexed on Medline or the Developmental and Reproductive Toxicology (DART) database through January 2005. The search terms used were: 'budesonide' and 'pregnancy'; 'pregnancy complications'; 'teratogens'; 'fetus'; 'embryo'; or 'toxicology'. The search was limited to English-language articles and those evaluating humans. Pertinent abstracts were identified from recent US asthma and allergy meetings.. A total of five articles and three abstracts meeting the search criteria were identified. Retrospective epidemiological studies and a randomized, placebo-controlled, multicenter trial found no clinically or statistically significant effects on fetal outcomes among more than 6600 infants whose mothers were exposed to orally inhaled budesonide during pregnancy. Women who reported use of orally inhaled budesonide either during early pregnancy only or throughout pregnancy gave birth to infants of normal gestational age, birth weight, and length, with no increased rate of stillbirths, multiple births, or congenital malformations. In a retrospective case-control analysis, no association was found between inhaled budesonide or intranasal budesonide and the overall rate of infant cardiovascular defects. However, a marginally increased risk of less severe cardiovascular defects (odds ratio = 1.58, 95% confidence interval 1.02 to 2.46) was observed with intranasal budesonide in one analysis, possibly the result of a random association due to multiple testing or an unidentified confounder.. Maternal exposure to orally inhaled budesonide during pregnancy is not associated with an increased risk of congenital malformations or other adverse fetal outcomes in studies of more than 6600 infants. Data on pregnancy outcomes after maternal exposure to intranasal budesonide are limited, but the totality of evidence, including pharmacological studies showing a much lower systemic exposure after intranasal administration, indicates its safety profile is at least comparable with that of orally inhaled budesonide.

Topics: Abnormalities, Drug-Induced; Administration, Inhalation; Administration, Intranasal; Administration, Oral; Asthma; Bronchodilator Agents; Budesonide; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Randomized Controlled Trials as Topic; Retrospective Studies; Rhinitis, Allergic, Perennial

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Topics: Acetates; Administration, Inhalation; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Quinolines; Salmeterol Xinafoate; Sulfides; Therapeutic Equivalency

On the basis of the well recognised role of inflammation in the pathogenesis of asthma, anti-inflammatory therapy, in the form of inhaled corticosteroids, has become the mainstay of treatment in patients with persistent asthma. Budesonide inhalation suspension (BIS) is a nonhalogenated corticosteroid with a high ratio of local anti-inflammatory activity to systemic activity. Furthermore, BIS is approved in >70 countries for the maintenance treatment of bronchial asthma in both paediatric and adult patients (approval is limited to paediatric patients in the US and France).Randomised, double-blind, placebo-controlled trials conducted in >1000 children have demonstrated the efficacy of BIS in children with persistent asthma of varying degrees of severity. In children frequently hospitalised with uncontrolled asthma, initiation of BIS therapy can reduce the need for emergency intervention. Moreover, limited data suggest that BIS is effective for the treatment of acute exacerbations of asthma in children and may reduce the need for short courses of oral corticosteroids.BIS is well tolerated in children, with an adverse event profile similar to that of placebo, and no clinically relevant changes in adrenal function have been demonstrated during the course of short- and long-term (1-year) studies. Small but statistically significant reductions in growth velocity have been demonstrated with BIS over 1 year of treatment. However, available evidence suggests that growth effects are transient in children receiving budesonide and that these children eventually achieve full adult height.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Humans; Infant; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

Combination therapy with inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is a recognized treatment for adults with moderate to severe asthma. The introduction of inhalers containing both an ICS and a LABA simplifies treatment and improves asthma control. This review discusses clinical evidence that budesonide/formoterol and salmeterol/fluticasone are effective and well tolerated in asthma treatment. Moreover, the rapid onset of effect and long duration of action of budesonide and formoterol make once-daily dosing, adjustable maintenance dosing, and the novel treatment strategy of using budesonide/formoterol for maintenance and as needed for symptom relief, valuable treatment options for patients with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans; Nebulizers and Vaporizers; Treatment Outcome

Medication for the treatment of asthma and chronic obstructive pulmonary disease should be given locally by inhalation. There is, however, no such thing as an ideal inhaler, or 'Idealhaler', which has all desired properties with no drawbacks. In this short review, we have compared the relative merits of the two most commonly used dry powder inhalers -- Turbuhaler and Diskus. Clinical effect is related to the amount of inhaled drug that reaches the lungs, and this in turn depends on the amount of fine particles generated at inhalation. Turbuhaler is more than twice as effective as Diskus at generating fine particles, and the higher lung deposition with Turbuhaler is accompanied by a lower variability in lung deposition. Compared with Diskus, the lung deposition with Turbuhaler is affected less by factors such as humidity.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Fluticasone; Humans; Nebulizers and Vaporizers; Particle Size; Pulmonary Disease, Chronic Obstructive

Different international guidelines recommend the early introduction of inhaled corticosteroids (ICS) and their regular use to gain clinical and functional control of persistent asthma. There is now evidence that the starting dose of all ICS is lower than previously regarded. Initial moderate ICS doses appear to be more effective than an initial low ICS dose. The lowest effective dose should always be seeked by a step-down procedure. More than 90% of benefit is achieved by approximately a daily regular dose of 200 microg of fluticasone or 400 microg of beclomethasone or budesonide. The beneficial effects of increasing the dose of ICS alone appear to be modest in most cases. Intermittent ICS therapy has been successfully used in the long term treatment of mild asthma. In general, twice-daily administration of ICS provides greater therapeutic benefit than a once-daily regimen in moderate asthma. When asthma control has been obtained, a once-daily regimen can be tried. In clinical practice, this has the potential advantage of increasing patients' compliance. Chlorofluorocarbon-free formulations of old ICS have also remarkably improved their clinical efficacy mainly through an increased peripheral deposition pattern. Despite some limitations due to poor response in neutrophilic asthma and to potential systemic side effects, ICS will certainly be the cornerstone of asthma therapy even the next future.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Fluticasone; Humans

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Delayed-Action Preparations; Down-Regulation; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Salmeterol Xinafoate; Treatment Outcome

Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. Although compliance to this type of medication is often suboptimal and once-daily dosing can help to improve adherence to the treatment, the clinical implications of such a mode of administration should be determined.. This review summarizes the recent studies on comparative efficacy of once-versus twice-daily administration of ICS, in light of previous reports.. Although twice-daily administration of ICS is often better to optimize asthma parameters, in many patients, asthma can be sufficiently controlled by a once-daily regimen of most ICS. An increased frequency of dosing seems preferable if asthma becomes uncontrolled or is severe, although this requires further study. A therapeutic trial should, however, be done to ensure that asthma control is adequate. Comparative long-term effects of such a strategy on inflammatory and remodeling parameters remain to be determined, as does the proportion of patients who can adequately control their asthma with once-daily administration of the various ICS available.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Treatment Outcome

The impact of long-term inhaled corticosteroid (ICS) therapy on bone mineral density (BMD) is poorly understood.. To evaluate the impact of long-term ICS use on BMD.. Random-effects meta-analysis. Published and unpublished literature were identified by searches of MEDLINE and EMBASE databases and consultation with experts. Studies reporting BMD among adult asthma and chronic obstructive pulmonary disease (COPD) patients using ICS and non-ICS controls were identified. Studies selected for review included at least 1 year of follow-up. Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted for inclusion in the meta-analysis.. Fourteen (5.3%) of 266 reviewed studies met specified inclusion criteria. Sufficient data were available to perform meta-analysis on 3 measures for ICS-using patients (lumbar, femoral neck, and major trochanter BMD) and 1 measure (lumbar BMD) for non-ICS-using controls. Using current National Asthma Education and Prevention Program definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of ICSs. Among ICS users, annual changes from baseline in lumbar, femoral neck, and major trochanter BMD (-0.23%, -0.17%, and +1.46%, respectively) were not statistically significant. Mean changes in lumbar BMD were also not significantly different from controls (-0.02%). Further, annual changes in lumbar BMD were not statistically significant for subgroups of patients with asthma or COPD.. Long-term use of ICSs in patients with asthma or COPD was not associated with significant changes in BMD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Budesonide; Fluticasone; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

Asthma, a chronic and potentially life-threatening disease of the airways, affects patients of all ages. Inhaled corticosteroids (ICS) are the recommended first-line therapy for patients with persistent asthma. To review the clinical efficacy and tolerability data available on budesonide in the treatment of mild-to-moderate persistent asthma, a MEDLINE database search was performed for 1996-2003 using the following key words: budesonide, inhaled corticosteroid, efficacy, safety, systemic. When administered once or twice daily, budesonide effectively controls asthma in children, adolescents, and adults with mild-to-moderate asthma. Budesonide can be delivered effectively via a dry powder inhaler (Pulmicort Turbuhaler) in patients aged > or = 6 years or as an inhalation suspension (Pulmicort Respules) in children as young as 12 months. With over 20 years' clinical exposure, budesonide has been demonstrated to be well tolerated in the treatment of chronic asthma in patients as young as 12 months. Specifically, at doses required to treat mild or moderate persistent asthma, budesonide does not affect hypothalamic-pituitary-adrenal axis function, bone mineral density, cataract formation, or final adult height. As Pulmicort Turbuhaler, budesonide is the only ICS to achieve a Food and Drug Administration pregnancy category B rating. Early intervention with budesonide is recommended in asthma management: maximum benefit from therapy is reported in patients treated within 2 years of disease recognition. Budesonide is effective and well tolerated in the control of mild-to-moderate persistent asthma in patients aged 12 months and older. There is no evidence for variation in efficacy in population subgroups.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bone Density; Budesonide; Cataract; Child; Child, Preschool; Female; Humans; Hypothalamo-Hypophyseal System; Infant; Male; Middle Aged; Pituitary-Adrenal System; Pregnancy; Pregnancy Outcome; Treatment Outcome

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma. A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhaler + spacer twice daily. A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 micrograms.day-1 was achieved at doses of approximately 200-400 micrograms.day-1 and 90% by 300-600 micrograms.day-1. Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of approximately 1,000 micrograms.day-1. In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhaler + spacer is achieved with a dose of approximately 400 micrograms.day-1 and the maximum effect is achieved at approximately 1,000 micrograms.day-1. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Randomized Controlled Trials as Topic; Regression Analysis; Remission Induction; Treatment Outcome

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma.. To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS.. We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: January 2003. Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS.. Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies).. 31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV(1) ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ). Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS.. For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Fluticasone; Humans; Randomized Controlled Trials as Topic

Budesonide and formoterol have been combined in a single dry powder device, Symbicort Turbuhaler (budesonide/formoterol 160/9-640/18 microg/day), in an effort to simplify asthma management. The efficacy of budesonide/formoterol as maintenance therapy in patients with asthma has been examined in several randomised studies.Twice-daily budesonide/formoterol was significantly more effective than an equivalent or higher daily dose of budesonide alone or high-dose fluticasone propionate alone at improving peak expiratory flow (PEF) in adults with predominantly moderate persistent asthma. Symptom control and the risk of mild exacerbations were significantly improved versus budesonide alone. Moreover, budesonide/formoterol appeared to be as effective as concurrent therapy with equivalent dosages of budesonide and formoterol administered via separate inhalers in adults with moderate persistent asthma. Budesonide/formoterol administered once daily was as effective as twice-daily administration (equivalent daily doses) and more effective than once-daily budesonide in adults with moderate persistent asthma. Twice-daily budesonide/formoterol significantly improved PEF compared with budesonide in paediatric patients with asthma. Adjustable maintenance dosing with budesonide/formoterol was associated with significantly less study drug use than fixed dosing with budesonide/formoterol in adults with predominantly mild or moderate persistent asthma. In two of three studies (all longer than 4 months' duration), the risk of exacerbations was significantly lower with adjustable than with fixed dosing, but no difference was detected in four short-term studies. Symptom severity was maintained or improved in most patients receiving either treatment regimen. In adults with moderate-to-severe persistent asthma, adjustable maintenance dosing with budesonide/formoterol reduced the rate of exacerbations and reliever medication use compared with fixed dosing with salmeterol/fluticasone propionate. Budesonide/formoterol was well tolerated in both fixed and adjustable dosing regimens. In conclusion, in patients with persistent asthma symptoms despite treatment with inhaled corticosteroids, budesonide/formoterol administered via a single dry powder Turbuhaler device is an effective, well tolerated, convenient treatment option, which may have the potential for improved compliance. It appears to be as effective as treatment with budesonide and formoterol administered via separate inhalers

Topics: Animals; Asthma; Budesonide; Clinical Trials as Topic; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans

Difficult asthma is defined as asthma that is not controlled despite treatment with> 800 micro g budesonide or equivalent per day. Poor control is defined as the need for bronchodilators more than three times a week, school absence of more than five days a term, or one episode or more of wheezing each month. Common causes of poor response to treatment include; wrong diagnosis, inappropriate medications or improper inhalation technique, poor adherence to medications and co-morbidity. Steroid resistant asthma is uncommon and estimated to be 1 in 1000-10000 asthmatic patients. If there is no functional improvement to prednisolone 2 mg/kg/day for 2 weeks with adherence checked by measuring serum prednisolone and cortisol levels, a fibreoptic bronchoscopic examination with bronchoalveolar lavage and large airway biopsy should be considered. Eosinophilic inflammation identified on the biopsy in a child who is unresponsive to prednisolone may benefit from alternative anti-inflammatory treatments such as cyclosporin. Neutrophilic infiltration in biopsy may benefit with macrolide antibiotics, 5-lipogenase inhibitors or theophyllines.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Drug Resistance; Glucocorticoids; Humans; Patient Compliance; Treatment Failure

Inhaled corticosteroids (ICSs) are the gold standard anti-inflammatory therapy for asthma and have been studied using a variety of different clinical trial designs. In long-term comparative studies ICSs are more effective in controlling asthma than beta-agonists or leukotriene antagonists (LTAs). Efficacy has also been shown retrospectively, as patients frequently experience an exacerbation of their asthma upon withdrawal of ICSs, whilst the regular use of low dose ICSs prevents death from asthma. The combination of ICSs with long-acting beta2-agonists (LABAs) is effective for patients with asthma non-responsive to low doses of ICSs, particularly in reducing exacerbations. In shorter term studies a modest dose-response effect of ICSs has been shown for lung function, symptom control and oral corticosteroid use in asthmatic patients. ICSs are also effective in reducing airway hyperresponsiveness (AHR) to various stimuli, as well as reducing exhaled nitric oxide (NO) concentrations and the number and activation state of a wide variety of inflammatory cells. Finally, using allergen challenge models even single doses of ICSs have profound inhibitory effects on the late asthmatic reaction. Since ICSs are the mainstay of asthma management guidelines, it is important that novel therapies should be judged against ICSs in future clinical trials. There are many potential designs for these comparative studies.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Allergens; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Budesonide; Dose-Response Relationship, Drug; Humans; Leukotriene Antagonists; Nitric Oxide; Randomized Controlled Trials as Topic; Treatment Outcome

Inhalation therapy delivers therapeutic agents directly into the lungs of patients with asthma, and is likely to remain the route of delivery of choice for the foreseeable future. The majority of patients with asthma suffer from mild intermittent to mild persistent disease for which regular low dose inhaled corticosteroids and on demand short-acting beta2-agonists have been recommended. These highly effective anti-asthma medications are readily available, and so in the future improvement in asthma therapy will most Likely derive from improvements in inhaler technology. Dry powder inhalers (DPIs) have many advantages compared to chlorofluorocarbon pressurised metered dose inhalers. Most notably, with DPIs patients no longer need to co-ordinate activation of the inhaler with inspiration. The Novolizer (VIATRIS, Germany) which is one of the latest developments in DPI technology offers a number of features required to increase the safety and efficacy of inhaled therapy. It is the first DPI to include an inspiratory trigger threshold, which helps to prevent sub-optimal dose administration. Repeated activation without inhalation is mechanically inhibited by an overdose prevention mechanism. In conclusion, there is good evidence that technically refined DPIs are more likely to advance inhaled anti-asthmatic therapy than newly developed inhaled drugs. This is important when inhalation therapy is considered not only for asthma but also for chronic obstructive pulmonary disease.

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Forced Expiratory Volume; Humans; Metered Dose Inhalers; Practice Guidelines as Topic; Product Surveillance, Postmarketing; Professional Practice; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Vital Capacity

The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Tolerance; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Metered Dose Inhalers; Salmeterol Xinafoate

The aim of this study was to examine the efficacy of budesonide administered once daily compared to twice daily in asthma.. Meta-analysis of randomised controlled trials comparing budesonide administered once versus twice a day that presented data on at least one clinical outcome measure was conducted.. A total of 10 studies, with 1922 children and adults with asthma, met the inclusion criteria. These studies were performed predominantly with mild to moderate asthmatic patients, using doses of budesonide ranging from 200 to 800 microg per day. There was no significant difference between daily dosing once or twice for all the clinical outcome variables, including withdrawals due to asthma, for which the odds ratio was 1.0 (95% confidence interval, 0.65-1.52).. In mild to moderate asthma a once-daily budesonide regimen has a similar efficacy to a twice-daily regimen in doses up to 800 microg per day. A once-daily regimen has potential advantages in terms of patient compliance and satisfaction, when used in clinical practice.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Respiratory Function Tests; Treatment Outcome

Budesonide, a widely used inhaled corticosteroid (ICS) with a favorable therapeutic ratio, is available via a dry powder inhaler (Pulmicort Turbuhaler) and as a suspension for nebulization (Pulmicort Respules).. MEDLINE and an AstraZeneca database were searched to identify relevant controlled clinical trials published between 1986 and 2002 using the key words budesonide OR inhaled corticosteroid, AND once daily.. Thirty-four controlled clinical studies involving once-daily administration of budesonide to asthmatic patients were identified. Excluding long-term studies, this review presents data from 23 controlled studies for 4466 adults or adolescents and 1532 children with asthma and demonstrates efficacy of budesonide in both corticosteroid-naïve patients and patients previously treated with ICS. Once-daily administration of budesonide achieves clinical efficacy comparable with that of twice-daily regimens in patients with mild-to-moderate asthma and is equally effective when given in the morning or evening. Once-daily administration simplifies treatment regimens and may improve patient compliance. The tolerability profiles of budesonide once-daily via Turbuhaler or as budesonide inhalation suspension are good and comparable with those for twice-daily dosing.. Once-daily budesonide is effective and well tolerated as initial treatment for adults and children with mild asthma and as maintenance therapy in patients with more severe asthma once asthma control has been achieved.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Randomized Controlled Trials as Topic

The introduction of inhaled corticosteroids (ICS) has been a milestone in asthma therapy. According to current guidelines ICS are the first line drug in chronic anti-inflammatory therapy. The purpose of first part of this publication is to present updated knowledge on mechanisms of anti-inflammatory action as well as some pharmacokinetics and pharmacodynamics data about commonly used ICS, especially fluticasone propionate (FP) and two others: budesonide (BUD), beclomethasone dipropionate (BDP). Some differences between mentioned drugs have been found concerning systemic activity and safety of therapy. Fluticasone propionate is twice as active as the BUD and BDP. First results of therapy are seen 1-2 week after administration. Fluticasone propionate, more lipophilic than other steroids, has also high glucocorticoid receptor affinity and specificity, high topical anti-inflammatory activity and low systemic bioavailability. Systemic availability of FP depends on absorption from respiratory system. Oral bioavailability can be neglected because of almost total inactivation in liver during first pass. Fluticasone propionate has some features of dissociated steroids which means predominance of transrepression over transactivation--beneficial from safety point of view. Clinical efficacy of FP in chronic asthma therapy in children was confirmed in many studies. It significantly reduces the symptoms and exacerbations of asthma. There is a close correlation between FP use and lung function tests. The therapy with FP decreases bronchial hyperreactivity and the use of systemic steroids and rescue medication. The beneficial action of fluticasone propionate in asthma is due its anti-inflammatory properties within the airways (decreasing levels of direct and indirect markers of airways inflammations are observed).

Topics: Administration, Inhalation; Adolescent; Age Factors; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Infant; Infant, Newborn; Male; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome

Inhaled corticosteroids (ICS) are known to reduce the risk of asthma exacerbations and asthma fatalities. In addition, an increased dose of ICS at the onset of exacerbation can reduce the need for systemic corticosteroids, although this may require a fourfold increase in dose. The overuse of short-acting beta(2)-agonists or long-acting inhaled beta(2)-agonists, used as monotherapy, increases these risks. By contrast, the use of long-acting beta(2)-agonists together with ICS has been demonstrated to reduce the doses of ICS needed for ideal asthma control, as well as to reduce asthma exacerbations. This has been best demonstrated in the Formoterol and Corticosteroids Establishing Therapy and Oxis and Pulmicort Turbuhaler in the Management of Asthma studies, which demonstrated that the combination of inhaled budesonide and formoterol reduced the risk of asthma exacerbations over that achieved by budesonide alone. Even the "as needed" use of inhaled formoterol added to ICS reduces asthma exacerbations. The combination inhaler, Symbicort, containing both budesonide and formoterol, reduced the risk of asthma exacerbations to a similar extent as the monocomponents, given separately. Treatment with either leukotriene receptor antagonists or anti-IgE also reduces the risks of asthma exacerbations, but the magnitude of the benefit compared with the combination of ICS and long-acting beta(2)-agonists is not yet known.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Humans; Leukotriene Antagonists; Nebulizers and Vaporizers

Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241-252.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child, Preschool; Cromolyn Sodium; Glucocorticoids; Humans; Infant; Leukotriene Antagonists; Recurrence; Respiratory Sounds; Theophylline

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 ( p=0.001) for healthy subjects, and ES=0.27 ( p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 ( p<0.01) at the lumbar spine, and 0.26 ( p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 microg (158 microg), BDP at 703 microg (123 microg) and TRI at 1,000 microg (282 microg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Bone Density; Budesonide; Fluticasone; Fractures, Bone; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

Asthma is a chronic inflammatory disease of the airways. Inhaled corticosteroids are recognized as the preferred long-term control medication for persistent asthma based on their anti-inflammatory properties and significant evidence of efficacy. Inhaled budesonide is the most carefully characterized inhaled corticosteroid for childhood asthma. It is available for administration in children down to six months of age and to date has an excellent safety profile.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bone Density; Budesonide; Child; Child Development; Child, Preschool; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Growth Disorders; Humans; Male; Nebulizers and Vaporizers; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome

Budesonide/formoterol (Symbicort), AstraZeneca plc) is a novel treatment for asthma, combining an inhaled corticosteroid - budesonide, and a long-acting beta(2)-agonist - formoterol, in a single inhaler, the Turbuhaler. Randomised, clinical studies in patients with asthma have demonstrated that budesonide/formoterol is more effective than the inhaled corticosteroids, budesonide and fluticasone alone, and at least as effective as both monocomponents in separate inhalers. Results from clinical studies suggest a synergistic effect when both drugs are administered via one inhaler, although the mechanisms for this are not fully understood. Budesonide/formoterol has a rapid onset of effect, apparent within 1 min of treatment, which is largely because of the properties of formoterol. Once- and twice-daily dosing with budesonide/formoterol are effective treatment options for patients with mild or moderate asthma. Studies have also shown that the beneficial safety profiles and dose relationships of both budesonide and formoterol allow dose adjustments of budesonide/formoterol in response to variations in the patient's asthma. Findings from the budesonide/formoterol adjustable maintenance dosing programme, comparing fixed and adjustable, symptom-guided dosing regimens, demonstrate that patients achieve equally good asthma control with adjustable dosing (from one inhalation twice-daily to more than four inhalations twice-daily), but at a significantly lower overall drug load. Adverse events, mainly expected inhaled corticosteroid and long-acting beta(2)agonist class effects, have been few in number and mild in nature. In addition, there is growing evidence that budesonide/formoterol is also effective in patients with chronic obstructive pulmonary disease. The future for treatment with budesonide/formoterol may include as-needed administration in addition to maintenance therapy.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Drug Synergism; Ethanolamines; Formoterol Fumarate; Humans

When asthma is being treated, it is essential that sufficient drug is deposited at the site(s) where it is needed. In recent years, many dry powder inhalers have been developed by the pharmaceutical industry. Drug delivery to the lung from dry powder inhalers is dependent upon the patient's peak inhaled flow rate, and so it is very important to be able to assess the amount and location of drug delivered from different devices. Lung deposition has recently been assessed from a new dry powder inhaler, the Novolizer (ASTA Medica, now VIATRIS GmbH & Co. KG, subsidiary Sofotec GmbH & Co. KG, Frankfurt, Germany), using gamma scintigraphy. It was shown that the Novolizer deposited significantly more budesonide in the lungs than a Turbuhaler used either at similar inspiratory flow rates or with similar inspiratory effort. Equivalent clinical efficacy and safety profiles have also been shown in asthmatic patients treated with budesonide from each device.

Topics: Administration, Inhalation; Aerosols; Anti-Inflammatory Agents; Asthma; Budesonide; Drug Delivery Systems; Humans; Lung; Nebulizers and Vaporizers; Patient Compliance; Powders; Pulmonary Ventilation; Radionuclide Imaging

Asthma is a chronic inflammatory disease of the bronchial tree, characterised by reversible obturation, bronchial mucosal inflammation and bronchial hyperresponsiveness. In the treatment of asthma, most important is avoidance of provoking allergens and regular anti-inflammatory treatment with inhaled glucocorticosteroids. For patients, very important is quick relief from asthma symptoms, this is why they prefer fast and long acting beta 2-agonists as a symptomatic treatment. Optimal control of asthma symptoms can be achieved with combination treatment consisting of inhaled glucocorticosteroid and beta 2-agonist. Budesonide is a corticosteroid that treats the underlying airway inflammation in asthma; formoterol is a fast and long-acting beta 2-agonist that prevents and reverses airway obstruction. Thus budesonide and formoterol have complementary effects, treating two different components of asthma. Clinical studies show that in the treatment of asthma Symbicort is more effective than double dose GCS, due to the budesonide/formoterol synergy. It is at least as effective, well tolerated and safe as its mono-products in corresponding doses given via separate inhalers. More convenient treatment represents an important benefit for patients with asthma. Symbicort is recommended for regular treatment and could also be used "as needed" due to the rapid onset of the bronchodilatory effect of formoterol.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Synergism; Ethanolamines; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive

Novolizer is a multidose breath-actuated dry powder inhaler (DPI) approved for use with salbutamol (albuterol) and budesonide. It has multiple patient feedback mechanisms and an inspiratory flow rate threshold designed to optimise dosage. In two studies, children aged 4-11 years with asthma correctly used Novolizer and generated mean peak inspiratory flow rates (PIFRs) through Novolizer of 76 and 92.7 L/min, well above the Novolizer threshold of 35-50 L/min. In healthy volunteers, median lung deposition of budesonide administered via Novolizer was 19.9-32.1% at mean PIFRs of 54-99 L/min. In a randomised, double-blind, single-dose study in patients with chronic obstructive pulmonary disease (COPD) and asthma, the 1-hour improvement from baseline in mean maximum forced expiratory volume in 1 second (FEV(1)) was 21.3% with inhalation of salbutamol through Novolizer, and 19.5% through Sultanol pressurised metered-dose inhaler (MDI). FEV(1) increased significantly in patients with asthma and COPD treated for 4 weeks in a randomised, open-label comparison of salbutamol through either Novolizer or Sultanol MDI. A randomised open-label study in adults with asthma treated with inhaled budesonide found equivalent improvements in FEV(1) and symptoms with Novolizer and Turbuhaler. Novolizer was well accepted overall. Most patients preferred it to previously used MDIs or DPIs. Only 4-5% found the taste feedback unacceptable. Physicians observed improved compliance over 4 weeks in 80% of patients with asthma using Novolizer.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Clinical Trials as Topic; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Powders; Pulmonary Disease, Chronic Obstructive

Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patients with untreated or undertreated asthma, which may lead to deterioration in disease control, with direct effects on morbidity and mortality rates. The costs attributed to asthma translate into a considerable economic burden, from the direct costs of medical treatment to the costs incurred through lost work or school days. International treatment guidelines currently recommend early intervention with ICS therapy to improve lung function and disease control.. This article reviews the role of therapy with ICSs, particularly budesonide, in improving the management of asthma in patients of all ages and in reducing the economic and social burdens of this disease.. Randomized, controlled clinical studies confirm the efficacy of early intervention with ICSs in patients with mild persistent asthma. Regular use of an ICS can reduce the number of exacerbations and hospitalizations in patients of all ages and with all disease severities.. Budesonide has a well-established efficacy and safety profile. Its once-daily dosing may contribute to improved adherence and cost-effectiveness.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Glucocorticoids; Humans; Randomized Controlled Trials as Topic

Since their introduction in the 1970s, inhaled corticosteroids (ICSs) have been used to control airway inflammation associated with asthma. Budesonide is one of the ICSs recommended as first-line therapy for mild to moderate persistent asthma.. This article describes the esterification of budesonide and how it results in prolonged, location-specific retention of drug in the airways, allowing once-daily dosing.. Studies conducted over the past decade have shown that budesonide forms reversible fatty acid esters within the cells of airway tissue, resulting in the formation of an intracellular depot pool of inactive drug. As the intracellular concentration of free budesonide decreases, these budesonide esters are hydrolyzed back to their active state. This process increases budesonide's retention in the airways, prolongs its duration of action, and lowers the risk of systemic effects.. By extending budesonide's local anti-inflammatory effect and increasing its airway selectivity, the esterification process appears to contribute to the drug's efficacy, particularly during once-daily administration. Reducing the number of required daily inhalations may increase patient compliance with asthma therapy, although this remains to be evaluated.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Esterification; Humans; Lung

The aim of inhaled corticosteroid (ICS) therapy for asthma is to attain high therapeutic activity in the airways while keeping the risk of systemic adverse effects relatively low. However, the physicochemical and pharmacokinetic properties of various ICSs affect this ratio, thereby influencing their ability to fulfill the requirements of an ideal agent.. This article reviews the physical and pharmacokinetic properties of budesonide, outlining how they, safety data, and use of different inhalation devices enable budesonide to meet many of the clinical requirements of an ideal ICS for the treatment of asthma.. ICS efficacy is influenced by lipophilicity, lung deposition, and retention in airway tissue, whereas the rate of elimination determines systemic activity. Budesonide is retained in the airways to a greater extent than other ICSs because of an esterification process that increases its lipophilicity. The prolonged retention of budesonide in the airways may contribute to its efficacy when administered QD. In addition to a pressurized metered-dose inhaler, budesonide is available as a dry-powder inhaler and in nebulized form, which can be used by asthma patients aged > or =6 months.. When combined with delivery devices suitable for a spectrum of patient groups, the physical and pharmacokinetic properties of budesonide lend it many of the characteristics of an ideal ICS, including favorable efficacy and tolerability profiles.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Esterification; Humans; Nebulizers and Vaporizers; Quality of Life; Randomized Controlled Trials as Topic

The therapeutic margin of a drug is the difference between the optimal effective dose and the dose at which unacceptable adverse effects occur. This margin is particularly important in the case of therapies that are used long term for the control of chronic illnesses, such as inhaled corticosteroids (ICSs) in the treatment of asthma. Because data from controlled clinical studies indicate that the available ICSs have similar clinical efficacy, the safety profile is central to differentiating between them on the basis of their therapeutic margins. The main safety concern with long-term use and high doses of ICSs is systemic exposure that could result in such unwanted effects as cortisol suppression, a reduction in the final adult height of pediatric patients, and decreased bone mineral density.. This article reviews data from clinical trials, including long-term prospective studies, to compare the therapeutic margin of budesonide with those of other second-generation ICSs and to determine whether there are variations in the therapeutic margin with different delivery devices, severities of disease, or patient age.. Based on the tolerability data for budesonide from short-term (6-12 wk) and long-term (1-9 y) studies in patients with mild to moderate persistent asthma, the dose-response and dose-tolerability curves for budesonide delivered by dry-powder inhaler can be plotted in parallel. The margin between these curves-the therapeutic margin-is favorable and consistent in pediatric and adult patients and at all degrees of asthma severity. Fewer tolerability data are available for other ICSS.. Whereas budesonide has clinical efficacy similar to that of other currently available ICSs, it has a good safety profile-and hence a favorable therapeutic margin-that is supported by long-term clinical data. Budesonides favorable therapeutic margin is probably a result of its pharmacokinetic and physical properties.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Nebulizers and Vaporizers; Quality of Life

Since the introduction of inhaled corticosteroids (ICSs) nearly 30 years ago, the management of asthma has been transformed. It is now understood that asthma is primarily a disease of chronic inflammation, even in its milder forms, and that to delay treatment may lead to deterioration in lung function. International treatment guidelines for asthma recommend early intervention with a potent ICS, with the greatest benefit observed when treatment is started within 2 years of the onset of symptoms. Each of the currently available ICSs has distinct physical and pharmacokinetic properties and is delivered via different devices.. This article brings together the findings and concepts presented in this supplement. It provides an overview of budesonide's predicted clinical efficacy and tolerability in patients with asthma based on its physical properties and pharmacokinetic and pharmacodynamic characteristics.. Budesonide's physical properties and pharmacokinetic and pharmacodynamic profiles help predict its clinical efficacy and tolerability when used as early intervention in asthma. Study results indicate that lung deposition of budesonide is increased by delivery via dry-powder inhaler, enhancing the drug's efficacy in patients with newly diagnosed mild persistent asthma. The preclinical, clinical, and safety data support budesonide's predicted performance in the clinical setting.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Clinical Trials as Topic; Humans

The worldwide prevalence of asthma is increasing by approximately 50% per decade. Budesonide is one of several inhaled corticosteroids available for the treatment of asthma and has been extensively evaluated in clinical trials.. This article reviews the published literature on the efficacy of budesonide in the management of adult and pediatric patients with moderate to severe asthma and compares budesonide with other inhaled corticosteroids and nonsteroidal treatment options.. All controlled, randomized studies in patients with moderate or severe asthma were considered for inclusion. Relevant studies were identified through a MEDLINE search of the period from 1980 to 2000 using the terms budesonide plus efficacy, with or without the termsfluticasone, mometasone, and beclomethasone. The manufacturer's reference database was used to identify additional publications.. Budesonide is associated with a dose-response effect in adults and children with moderate to severe asthma. The data on budesonide are in line with the current recommendation for a high starting dose of inhaled corticosteroid (800 microg/d), followed by downward titration to the minimal effective dose. Budesonide administered by Turbuhaler (AstraZeneca Pharmaceuticals LP, Wilmington, Del) dry-powder inhaler (DPI) was effective at a significantly lower dose than beclomethasone dipropionate (BDP) administered by pressurized metered-dose inhaler (pMDI) (P = 0.009), whereas its efficacy was similar to that of BDP delivered by hydrofluoroalkane pMDI and that of fluticasone propionate administered by DPI. Inhaled budesonide therapy was shown to be oral corticosteroid sparing in patients with severe asthma, thus reducing the total corticosteroid dose and the risk of systemic side effects. Pulmicort Respules (AstraZeneca), a nebulized formulation, was effective in the treatment of moderate to severe asthma in patients aged > or =12 months.. Once- or twice-daily administration of budesonide delivered via the Turbuhaler and Pulmicort Respules systems has been shown to be well tolerated and efficacious in populations with moderate to severe asthma.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

Patients with mild intermittent or mild persistent asthma represent 70% of asthma sufferers. Inhaled corticosteroids (ICSs) are the mainstay of treatment for persistent asthma, although many of the early clinical studies of these drugs included only patients with moderate to severe asthma.. This article reviews the literature on the efficacy of budesonide in the treatment of mild persistent asthma, including newly diagnosed ICS-naive patients.. Published data were identified by a MEDLINE search of the English-language literature from 1992 to 2002 using the terms budesonide plus efficacy or safety, both with and without the termsfluticasone or beclomethasone. An AstraZeneca reference database was also used to identify publications from the same period. Controlled, randomized studies that included patients with mild persistent asthma and early-treatment intervention were selected for inclusion.. Inhaled budesonide has been used for almost 20 years in the treatment and control of moderate to severe asthma. Studies involving patients with mild persistent asthma have demonstrated significant improvements in peak expiratory flow (PEF) rates (P < 0.01) and forced expiratory volume in I second (P < 0.016) values for adult, adolescent, and pediatric patients treated with budesonide compared with placebo. Budesonide therapy is effective when given once or twice daily via dry powder inhaler or nebulizer, even at a low starting dose (200 microg/d). No significant adverse events have been reported with budesonide within the dose range used to treat mild persistent asthma (200 to 400 microg/d). Significant improvements in PEF rates (P < 0.01) and significant reductions in the risk of exacerbations and the number of days with poorly controlled asthma have been reported for ICS-naive patients treated with budesonide compared with placebo (both P < 0.001). In the primary care setting, mild persistent asthma may be undertreated. Patients with mild persistent asthma benefit significantly from early treatment with budesonide (P < 0.05).. Budesonide is effective and well tolerated in the treatment of mild persistent asthma in adults and children, including many patients whose primary care physicians do not think they require daily ICS treatment.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Humans; Time Factors; Treatment Outcome

Airmax is a multi-dose dry powder inhaler. An internal pump measures out the drug dose using controlled air pressure. Inhalation transports the drug into a cyclone separator (where active drug is separated from the lactose carrier) and then into the patient airway. In vitro studies indicate that Airmax may be less dependent on airflow than Turbuhaler for drug delivery; greater dose consistency was seen with administration of budesonide via Airmax than via Turbuhaler. At a low flow rate, the lung deposition of budesonide administered via Airmax was greater than that of budesonide administered via Turbuhaler or a pressurised metered dose inhaler in patients with asthma. In cumulative-dose studies, the mean forced expiratory volume in 1 second (FEV(1)) achieved with salbutamol (albuterol) or formoterol administered via Airmax was equivalent to that achieved with twice the dose administered via dry powder inhalers. black triangle In randomised, double-blind studies, budesonide administration via Airmax was equivalent to administration via Turbuhaler with regards to FEV(1) and improvement in asthma symptoms in both adults and children with asthma. The concentration of adenosine monophosphate producing a 20% fall in FEV(1) increased from pretreatment levels by a greater extent with budesonide administered via Airmax, compared with Turbuhaler. Both adults and children preferred Airmax to Turbuhaler, and more found Airmax easier to use. In one study, the majority of children found learning how to use Airmax trade mark easier than learning how to use Turbuhaler.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Equipment Design; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Powders; Randomized Controlled Trials as Topic; Treatment Outcome

Maintenance treatment for mild asthma frequently comprises both a regular inhaled corticosteroid and an 'as required' inhaled short-acting beta 2-agonist. Where such treatment fails, additional regular treatment with an inhaled long-acting beta 2-agonist is increasingly recommended. In the UK, combination inhalers containing salmeterol + fluticasone ([symbol: see text] Seretide--Allen & Hanburys) or formoterol + budesonide ([symbol: see text] Symbicort--AstraZeneca) are licensed for use either in "patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short-acting beta 2-agonists" or in "patients already adequately controlled on both inhaled corticosteroids and long-acting beta 2-agonists". Here we review the efficacy of Seretide and Symbicort and discuss their place in asthma management.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Costs; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Randomized Controlled Trials as Topic

To provide product information; review and analyze the clinical literature studying combination therapy, budesonide, and formoterol in asthmatics; and to define the role for this therapy in asthma treatment.. A MEDLINE search (1990-September 2001) was conducted to identify the primary literature. Bibliographies were reviewed for further relevant citations.. All randomized, blinded, controlled studies at least 3 months in duration exploring the efficacy of the combination of budesonide and formoterol (in 1 or separate formulations) compared with other treatments were selected to be included in the review of clinical studies.. The combination of budesonide and formoterol was more effective than increasing the dose of budesonide in patients with moderate or severe persistent asthma and in patients with mild asthma not previously controlled with inhaled corticosteroids. Milder corticosteroid-naïve asthmatics did not derive benefit compared with inhaled corticosteroids alone.. Combination therapy in 1 device is a preferred treatment option in patients with moderate to severe persistent asthma and in those with milder asthma not controlled with inhaled corticosteroids. Advantages of this product include rapid onset of action, long duration of action, and a wide dosing range to assist with titration. Further research is required to evaluate this therapy in asthmatic children <5 years old and in patients with oral corticosteroid-dependent asthma. Investigations into the effect of this combination product on other disease outcomes, such as quality of life and productivity, will further define the role for this drug therapy.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Powders

The clinical value of corticosteroids in treating asthma has long been recognised. Major advances in the use of these drugs came with the introduction of inhaled corticosteroids (ICS) and the recognition that even mild asthma has an inflammatory component. ICS are now considered as first-line therapy in all asthma treatment guidelines. Over the past decade there has been clarification of the dose-response relationship with ICS and confirmation of the general long-term efficacy and safety of these drugs in both adults and children. Recent work has focused on simplifying dosing regimens and investigating flexibility of dosing. Moreover, ICS can be used in combination with other agents such as long-acting inhaled beta(2)-agonists to provide effective asthma control in patients with persistent asthma not adequately controlled on ICS alone. Thus, ICS remain the cornerstone of modern asthma therapy.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Budesonide; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Humans

Asthma varies in severity over time; consequently, treatment regimens must be sufficiently flexible to be adjusted when necessary. At present, inhaled corticosteroids (ICS) remain the cornerstone of asthma therapy and optimal treatment strategies must consider total daily dose and dosing frequency. The dose responsiveness to ICS varies for different indices of asthma. Symptoms and lung function respond readily to low-dose ICS and the dose-response curve is relatively flat. In contrast, the prevention of asthma exacerbations displays a more pronounced dose-response relationship. In mild asthma, once-daily dosing with budesonide is as effective as twice-daily dosing. However, in moderate-to-severe asthma, four-times daily dosing is better than twice-daily dosing for obtaining maximal benefit with minimal side effects. A flexible treatment regimen, consisting of low-dose maintenance treatment combined with high dose and frequently dosed ICS at the earliest sign of an exacerbation, has been shown to be effective. This could be achieved using a single inhaler combination product if the beta(2)-agonist moiety allows for the same flexibility in dosing. Formoterol, with its wide dose range, rapid onset and long duration of effect, has the pharmacological features that permit this versatile, flexible dosing. As a result, Symbicort would seem to offer the flexibility required in a single inhaler for maintenance and reliever purposes in the management of this variable disease.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Clinical Trials as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans

For patients whose asthma is not adequately controlled with inhaled corticosteroid (ICS) therapy alone, increasing the dose of ICS or the addition of a long-acting beta(2)-agonist is recommended. Greater improvements in lung function are achieved with the addition of a long-acting beta(2)-agonist to ICS therapy, rather than doubling the dose of ICS. Formoterol and salmeterol have a similarly long duration of effect (up to 12 h). However, as a result of their different chemical structures, there are marked pharmacological differences in the mechanism of action which affect their speeds of onset. These differences amount to a more rapid onset of effect for formoterol compared with salmeterol. Long-acting beta(2)-agonists appear to be well tolerated at elevated doses. These two features (tolerability at high doses and rapid onset of effect) support the use of formoterol as a reliever medication in addition to use in maintenance therapy. The long-acting beta(2)-agonists can be considered as beneficial additions to ICS therapy for the management of moderate-to-severe asthma.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Salmeterol Xinafoate

Symbicort is a novel asthma product containing both budesonide and formoterol in a single inhaler, Turbuhaler. Budesonide is a corticosteroid that treats underlying airway inflammation in asthma; formoterol is a rapid- and long-acting beta2-agonist that prevents and reverses airway obstruction. Budesonide and formoterol therefore have complementary effects, treating two different components of asthma. Clinical studies have shown that Symbicort is more effective in the treatment of asthma than double-dose corticosteroid, and clinical experience to date indicates that Symbicort is at least as effective and well tolerated as budesonide and formoterol given in separate inhalers. Symbicort has a fast onset of effect, which may help patients feel more in control of their condition and improve adherence to their medication, and a long duration of effect that allows twice-daily or even once-daily dosing during periods of good control. More convenient treatment represents another important benefit for patients with asthma, as ease of use can also result in improved adherence, leading to better disease control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Treatment Outcome

A small effect (1 cm) of inhaled corticosteroids (ICS) on the 1-year growth of asthmatic children was observed in studies published during the 1990s. A high volume of literature published during the past year confirmed mild growth suppression at one year, but provided information on the effects of longer-term treatment. These developments are important, since the effect was previously unknown and the findings have major implications for asthma caregivers and the communication that they have with asthmatic children and their parents. The possibility that this is an idiosyncratic effect received conflicting support. These studies collectively provide support for ICS use and ease the minds of caregivers, parents, and children. The risk of growth retardation can be lessened and managed by the employment of several simple strategies: (1) monitor growth; (2) use the minimal effective dose; (3) optimize steroid-sparing strategies (smoke and allergen environmental controls, vaccinate for influenza, diagnose and treat rhinitis, sinusitis, and gastroesophageal reflux disease, use add-on therapy with a second controller rather than doubling the ICS dose if control is inadequate); and (4) use spacing devices (for pressurized metered-dose inhalers) and mouth rinsing. Open and accurate communication with patients and parents about this possible effect is essential to minimize nonadherence. Ultimately, no child whose disease severity warrants ICS therapy should be denied the tremendous benefits that this therapy can provide because of relatively minor concerns about growth effects.

Topics: Androstadienes; Asthma; Body Height; Budesonide; Child; Fluticasone; Glucocorticoids; Humans; Respiratory Function Tests

Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Drug Therapy, Combination; Fluticasone; Humans; Leukotriene Antagonists; Salmeterol Xinafoate; Triamcinolone Acetonide

To evaluate the role of budesonide inhalation suspension (BIS) in the treatment of children with asthma.. Literature identified through Medline (1966-November 2000) and references obtained from selected articles. Search terms included budesonide and asthma.. Asthma is a chronic inflammatory disease that affects approximately 4.8 million children in the US. By reducing inflammation, corticosteroids decrease symptoms and improve lung function. As the first nebulized corticosteroid, BIS offers an important treatment option for children with persistent asthma.. BIS is effective in reducing symptoms and improving lung function in children with asthma. It should be used in children ages 1-8 years with moderate to severe persistent asthma who are unable to effectively use a metered-dose inhaler with or without a spacer or a dry-powder inhaler.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Humans; MEDLINE; Randomized Controlled Trials as Topic; Suspensions; Treatment Outcome

Inhaled corticosteroids reduce airway inflammation and bronchial hyper-responsiveness in asthma. Their regular use is associated with a reduction in morbidity and mortality from asthma. International guidelines recommend their use as first-line treatment in asthma and the dose should be increased stepwise in accordance with asthma severity. Short-acting beta2-agonists are recommended for use as reliever medication for the acute relief of symptoms. Long-acting beta2-agonists have a sustained bronchodilator action but are not recommended for use as monotherapy in asthma, particularly because they lack clinically relevant anti-inflammatory action. The seminal observation in a controlled trial that the addition of salmeterol to low-dose inhaled beclomethasone dipropionate was superior to doubling the dose ofthe beclomethasone dipropionate was followed by several well-controlled studies that confirmed this observation. These included multinational and multicentre trials in large numbers of patients and the use of different inhaled corticosteroids and the two long-acting beta2-agonists, formoterol and salmeterol. Therefore level A evidence (randomized controlled trials with a rich body of evidence) is available for this recommendation. Based on this, updated asthma guidelines recommend the addition of long-acting beta2-agonists for chronic asthma that is at least moderately severe or mild asthmathat is not well controlled with low-dose inhaled corticosteroids. Attention was therefore focused on developing combination inhalers that included inhaled corticosteroids and long-acting beta2-agonists in order to simplify asthma treatment and improve adherence to prescribed medication. Symbicort Turbuhaler (budesonide/formoterol in a single inhaler) is one such development. Studies to date in over 800 adult patients have confirmed that budesonide/formoterol is superior to double the dose of budesonide monotherapy and at least as effective and safe as budesonide and formoterol in separate inhalers, These studies also demonstrate that there are no physico-chemical interactions when the two medications are combined in a single inhaler. Symbicort in its easy to use formulation and inhaler device represents a valuable addition to the pharmacological management of asthma.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate; Treatment Outcome

Asthma is now widely recognized as a chronic inflammatory condition of the airways that requires early pharmacological treatment and long-term management. Anti-inflammatory agents, particularly inhaled corticosteroids, are currently the most effective long-term preventative medication. Moreover, early intervention with inhaled corticosteroids plays an important role in airway remodelling. Despite significant advances in the understanding of asthma and its pharmacological management, the prevalence of asthma in children, teenagers and young adults is on the increase. For patients whose asthma is not fully controlled with daily inhaled corticosteroid therapy, national guidelines advocate the addition of long-acting inhaled beta2-agonist therapy, rather than an increase in dose of inhaled corticosteroids, for the treatment of persistent childhood asthma. However, adherence to treatment with asthma medication declines as the regimen becomes more complicated. Adherence to therapy and therapy convenience are key to the successful pharmacological management of asthma, particularly in children. The administration of prescribed medication via a single inhaler offers a convenient treatment regimen that has the potential to improve adherence to treatment. This paper presents data to show that the combined administration of budesonide and formoterol via a single inhaler (Symbicort Turbuhaler) is effective and well tolerated in the treatment of asthma in children.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Infant; Infant, Newborn; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Practice Guidelines as Topic; Treatment Outcome

Asthma is a chronic inflammatory disease of the airways involving a wide range of cells and mediators. First-line therapy of persistent asthma involves the use of inhaled corticosteroids to control the underlying inflammation of the airways. Inhaled beta2-agonists are also widely used in asthma therapy and are the most effective bronchodilators currently available. The short-acting beta2-agonists are now used on an as-needed basis for rapid relief of symptoms, In recent years, long-acting inhaled beta2-agonists have had an increasing role in the management of asthma, particularly in patients with moderate to severe asthma. This class of drug has a long duration of action and is recommended as add-on treatment to inhaled corticosteroids in the long-term control of asthma. New therapies have been added to asthma therapy as our understand ng of the pathogenesis of asthma has increased. The use of multiple therapies necessitates a clear understanding of the mode of action of the drugs and any potential interaction or overlap of effect. For many people asthma is associated with complex therapy; thus treatment developments that simplify asthma treatment are an mportant step forward n asthma management.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Formoterol Fumarate; Humans; Leukotriene Antagonists; Macrophages; Mast Cells; T-Lymphocytes

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physic an education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort is more cost-effective than treatment with budesonide alone.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Australia; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Canada; Child; Cost-Benefit Analysis; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Quality of Life; Sweden; Treatment Outcome; United Kingdom; United States

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 42 studies (>10,000 patients) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01, 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5, 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1, 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.77, 95%CI 0.54, 1.10). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.42, 3.28) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic characteristics. It is unclear whether this translates into clinically significant differences in efficacy or safety when treating children and adults with chronic asthma.. To assess clinical outcomes in studies which have compared inhaled BDP and BUD in the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Prospective, randomised trials comparing BDP to BUD in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 24 studies met the criteria for inclusion (1174 subjects). Methodological quality was variable. A meta-analysis of crossover studies did not demonstrate a significant difference between BDP and BUD for FEV1, morning PEF, evening PEF, asthma symptoms or rescue beta2 agonist use, over a dose range of 400 to 1000 mcg/d. The majority of crossover trials had significant design flaws related to a lack of washout and/or failure to exclude carryover effects so the results must be viewed with caution. A single crossover study with adequate washout showed that BUD 400 mcg/d delivered via Turbohaler dry powder inhaler (DPI) may be more effective than BDP 400 mcg/d delivered via Rotahaler DPI in reducing histamine bronchial hyper-responsiveness: Weighted Mean Difference (WMD) 0.43 log10 PC20 FEV1 (95% Confidence Intervals (CI) 0.05, 0.81 log10 PC20 FEV1). A meta-analysis of two parallel group, dose down-titration studies (231 patients) showed that less BUD delivered via a Turbohaler DPI was required to maintain control in adults asthmatics compared to BDP delivered via metered dose inhaler with or without a spacer: WMD 444 mcg/d (95% CI 332, 556 mcg/d).. There is limited high quality randomised controlled trial data comparing the relative efficacy of BDP and BUD. Current guidelines (BTS 1997, GINA 1995, NHLBI 1997) assume BDP and BUD to have equal efficacy, such that for each defined level of asthma severity, the recommended doses BDP and BUD are the same. Although there is some data to suggest that BUD via Turbohaler is more effective than BDP via either Rotahaler or MDI (with and without spacer), these comparisons are confounded by use of different delivery devices, and are not sufficient to warrant a change in guideline recommendations.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

Guidelines for managing asthma in pediatric patients published by the American Academy of Allergy, Asthma, and Immunology and the American Academy of Pediatrics recommend the use of inhaled corticosteroids for the management of persistent asthma in infants and young children. When these guidelines were published, pressurized metered-dose inhalers and dry-powder inhalers were the only delivery devices available for inhaled corticosteroids in the United States. These devices can be difficult for young children to use correctly. Furthermore, no inhaled corticosteroid was approved in the United States for the treatment of children younger than 4 years. Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, Del) was developed to meet the medication delivery needs of infants and young children with persistent asthma. Pulmicort Respules is the first inhaled corticosteroid approved for administration by means of a nebulizer and the only inhaled corticosteroid approved in the United States for infants as young as 12 months. Budesonide has been studied extensively worldwide. In the United States the tolerability and efficacy of budesonide inhalation suspension were confirmed in 3 placebo-controlled multicenter trials. These studies demonstrated that both once- and twice-daily dosing of budesonide inhalation suspension (0.25-1 mg) improved pulmonary function and ameliorated asthma symptoms in infants and young children with persistent asthma. Budesonide inhalation suspension was well tolerated, and the incidences of reported adverse events were similar among patients in the budesonide, placebo, and conventional asthma therapy groups. This article reviews the results of these studies, as well as the pharmacokinetics, pharmacodynamics, and clinical use of budesonide inhalation suspension.

Topics: Administration, Inhalation; Age Factors; Asthma; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Guidelines as Topic; Humans; Incidence; Infant; Nebulizers and Vaporizers; Suspensions

Oral corticosteroids (CS) are standard treatment for patients discharged from the emergency department (ED) after treatment for acute asthma. Several recent, relatively small trials have investigated the replacement of CS with inhaled corticosteroids (ICS), with varied results and conclusions. This systematic review examined the effect of using ICS in place of CS on outcomes in this setting.. Only randomized controlled trials were eligible for inclusion. Studies in which patients were treated for acute asthma in the ED or its equivalent, and on discharge compared ICS therapy to standard CS therapy, were eligible for inclusion. Trials were identified using the Cochrane Airways Review Group register, searching abstracts and bibliographies, and contacting primary authors and pharmaceutical companies. Data were extracted and methodologic quality assessed independently by two reviewers, and missing data were obtained from authors.. Seven trials, involving a total of 1,204 patients, compared high-dose ICS therapy vs CS therapy after ED discharge. There were no significant differences demonstrated between the treatments for relapse rates (odds ratio, 1.00; 95% confidence interval, 0.66 to 1.52) or in the secondary outcomes of beta-agonist use, symptoms, or adverse events. However, the sample size was not adequate to prove equivalence between the treatments, and severe asthmatics were excluded from these trials.. There is some evidence that high-dose ICS therapy alone may be as effective as CS therapy when used in mild asthmatics on ED discharge; however, there is a significant possibility of a type II error in drawing this conclusion.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Emergencies; Fluticasone; Humans; Patient Discharge; Randomized Controlled Trials as Topic

The use of histamine and methacholine is well established for identifying airway hyperresponsiveness (AHR) but the AHR to these agents is not specific for asthma diagnosis. Further, these agents do not identify or exclude exercise-induced asthma (EIA) so they are inappropriate for some occupational and sporting assessments. Measurement of AHR by pharmacological agents has other limitations in that a positive response does not necessarily identify a person who will respond to inhaled steroids and responses do not differentiate between doses of steroids. As most asthmatics remain hyperresponsive to these agents after treatment they have not been useful for guiding steroid dose reduction. Bronchial provocation tests (BPTs) with physical stimuli such as exercise, eucapnic voluntary hyperpnea and hypertonic saline have provided useful information on presence and severity of asthma and EIA. These tests however, can be time consuming and require more resources compared with the pharmacological tests. To simplify testing, a challenge has been developed that uses a dry powder of mannitol administered from a simple hand-held device. The mannitol is given in increasing doses from capsules containing from 5 mg to 40 mg. Mannitol responsiveness identifies people with EIA and those who will respond to inhaled steroids. Mannitol responsiveness is reduced following treatment with inhaled steroids, and some subjects become unresponsive within 6 to 8 weeks. Responsiveness to mannitol can be used to predict risk of exacerbation during back titration of steroids. Should this BPT become more readily available it would be the first to provide a common operating standard for use in the laboratory, office, or field.

Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Forced Expiratory Volume; Humans; Mannitol; Saline Solution, Hypertonic

Evidence is accumulating that budesonide (BUD) forms intracellular esters in airways. which may affect both duration of action and therapeutic ratio of this drug. The aim of the present paper is to review the preclinical and human experimental evidence supporting the esterification of BUD, and to discuss the clinical implications this may have on asthma and rhinitis treatment.. After inhalation, intact BUD binds primarily to available steroid receptors, and mainly excess (unbound) BUD is esterified. Esterification of BUD is a rapid process: within 20 minutes of inhalation in the rat of radiolabeled BUD, approximately 80% of radioactivity within the trachea and main bronchi was associated with BUD esters, primarily BUD oleate. After 4 hours, the proportion of BUD esters/total cellular BUD was typically 40 to 50% for lung, 70 to 90% for trachea, and only 10 to 15% for peripheral muscle. Comparative in vitro and in vivo studies have shown that esterification prolongs BUD's anti-inflammatory activity longer than that of corticosteroids that can not form esters. Clinical studies have confirmed the prolonged presence of BUD esters, as well as intact BUD, in human airway tissues: 6 hours postdosing, nasal biopsy concentrations of intact BUD were >10-fold greater than those of fluticasone propionate and at 24 hours BUD was detectable in threefold more biopsies than fluticasone propionate. The impact of esterification on airway selectivity of BUD has also been demonstrated in vivo and using pharmacokinetic/pharmacodynamic models.. BUD is retained in airways as esters, a novel kinetic mechanism for synthetic glucocorticoids. In preclinical studies this esterification is correlated to a prolonged local tissue binding and efficacy, which is not found when the esterification is inhibited by an esterification blocker. Because less esters are formed in the systemic compartment than in airways/lung, the local benefit:systemic risk ratio may also be improved by this mechanism. BUD possesses favorable clinical properties, including its approved once-daily efficacy in asthma, which is probably in part attributable to esterification. However, a direct proof of the latter in patients requires effective and safe inhibitors of the esterification, which are not yet available. Therefore, evidence to support the therapeutic impact of esterification is still circumstantial.

Topics: Animals; Asthma; Bronchodilator Agents; Budesonide; Fatty Acids; Humans; Rhinitis

Asthma is recognized as an inflammatory disease, and inhaled corticosteroids are the mainstay of treatment in patients with persistent disease. Until recently, no inhaled corticosteroid was approved in the United States for children aged 4 years and younger, and no practical dosage form was available for infants and young children unable to use metered-dose inhalers effectively. Budesonide inhalation suspension (BIS) is a glucocorticoid with high topical and low systemic activity. In children aged 12 months-8 years, BIS improves asthma symptoms and lung function and decreases the need for breakthrough bronchodilators. Long-term follow-up studies in children concluded that BIS is well tolerated, with little or no effect on growth and hypothalamic-pituitary-adrenal axis function. Thus it is a valuable therapeutic alternative to systemic corticosteroid therapy in infants and young children.

Topics: Adrenocorticotropic Hormone; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Controlled Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Hydrocortisone; Infant; Male; Peak Expiratory Flow Rate

Current evidence suggests that the addition of the long acting inhaled beta2-agonist formoterol to low or moderate doses of the inhaled corticosteroid budesonide is effective in improving lung function and reducing the incidence of asthma exacerbations. Concurrent use of budesonide with formoterol does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles. The administration of combined budesonide/formoterol is effective in improving morning and evening peak expiratory flow rates in adults with persistent asthma. Control of asthma symptoms is also significantly improved. In children aged 4 to 17 years, combined budesonide/formoterol is effective in increasing both morning and evening peak expiratory flow rates and significantly improving forced expiratory volume in 1 second (FEV1). The most commonly encountered adverse effects in clinical trials with combination budesonide/formoterol therapy have been respiratory infection, pharyngitis and coughing. No adverse effects on pulse rate, blood pressure or serum potassium have been reported with combination therapy.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

Topics: Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans

The class label warning in the United States for inhaled corticosteroids (ICS's) states that these drugs may reduce growth velocity in children. In this paper, the evidence for this warning is reviewed from a clinical point of view. Children with asthma tend to grow slower than their healthy peers during the prepubertal years because they go into puberty at a later age. However, asthmatic children do achieve a (near) normal adult height. In randomized controlled clinical trials, the use of inhaled beclomethasone, budesonide and fluticasone is associated with a reduced growth during the first months of therapy, in the order of magnitude of approximately 0.5-1.5 cm x yr(-1). It is, however, unlikely that such an effect continues or persists because accumulating evidence shows that asthmatic children, even when they have been treated with ICS for years, attain normal adult height. Individual rare cases have been reported, however, where ICS use was associated with clinically relevant growth suppression. Inhaled corticosteroids are the most effective therapy available for maintenance treatment of childhood asthma. Fear of reduced growth velocity is based on exceptional cases and not on group data. It should, therefore, not be a reason to withhold or withdraw such highly effective treatment in children with asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biological Availability; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Glucocorticoids; Growth; Humans

Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear.. To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999).. Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1.. Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery.. Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Delivery Systems; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.. Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone.. Medline, Embase, and GlaxoWellcome's internal clinical study registers.. FEV(1), morning and evening peak expiratory flow, night awakenings, beta agonist use, and major exacerbations.. Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 microg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 microg/day and peaked by 500 microg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 microg/day was achieved at doses of 70-170 microg/day and 90% by 100-250 microg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 microg/day. The odds ratio for patients remaining in a study at a dose of 200 microg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV(1 )for an inhaled dose of 200 microg/day against higher doses showed a difference in FEV(1) of 0.13 of a standard deviation (-0.02 to 0.29).. In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 microg, and the maximum effect is achieved with a dose of around 500 microg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 microg/day.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Odds Ratio; Randomized Controlled Trials as Topic

Current asthma management guidelines state that where a patient is receiving a low to moderate dose of inhaled corticosteroids and is still experiencing symptoms the dose of corticosteroid should be increased and, if necessary, a long-acting bronchodilator should be added. Many studies have now shown that the addition of a beta2-agonist with long-acting properties is more effective at controlling asthma symptoms than increasing the dose of corticosteroid alone. The Formoterol and Corticosteroid Establishing Therapy (FACET) study was a 12-month study comparing exacerbation rates in patients treated with budesonide (100 microg or 400 microg) twice daily alone vs, treatment with budesonide (100 microg or 400 microg) twice daily plus formoterol 9 microg twice daily (delivered dose). The addition of formoterol reduced the rates of mild and severe exacerbations compared with budesonide alone, with the lowest rates seen in patients receiving high-dose budesonide and formoterol. There was no difference in the profile of exacerbations in any groups, indicating formoterol does not mask any signs of inflammation. The addition of formoterol to budesonide was also shown to result in improved lung function (as measured by peak expiratory flow rate and forced expiratory volume in 1 second), night-time awakenings and the use of as-needed medication when compared with an increase in the dose of budesonide. In all cases, increasing the dose of budesonide and addition of formoterol resulted in the most improvement and a significant increase in quality of life, measured by Asthma Quality of Life Questionnaire (AQLQ), was noted. In conclusion, the addition of formoterol to established treatment with inhaled corticosteroids provides superior asthma control compared with an increase in the dose of corticosteroid alone.

Topics: Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2

Topics: Administration, Topical; Adrenergic beta-Agonists; Adult; Age Factors; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Meta-Analysis as Topic; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Receptors, Glucocorticoid; Respiratory Therapy; Salmeterol Xinafoate; Time Factors

The pathology of asthma has clarified that the inflammatory process in the pulmonary airways of the asthmatic patients determines asthma symptom activity primarily. Among the anti-inflammatory agents currently available to treat asthma, glucocorticoids are the most effective, and the topically active agents, inhaled corticosteroids (ICS) are the most efficient. In Japan, two ICS are commercially available: beclomethasone dipropionate (BDP) and fluticasone propionate(FP). Both agents have been widely used and their clinical efficacy (BDP vs FP at half the microgram dose of the BDP) are largely comparable. In order to bring asthmatic patients maximal benefits of the ICS, enhancing treatment compliance and giving educations (including how to use the ICS) are mandatory. New ICS, which have better drug delivery and be topically more potent, will be available.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Patient Education as Topic; Pregnenediones

Inhaled corticosteroid therapy against bronchial asthma has developed rapidly and remarkably during last 10 years. The significance of this therapy has been established in a lot of international guidelines for asthma management. Early intervention, which developed from the concept of step-down therapy, is new therapeutic approach to prevent the remodeling of airway walls deemed as the major cause of irreversible airflow limitation which makes patient chronic and refractory asthmatics. It is comprehensive therapeutic approach which include not only early diagnosis, early intensive corticosteroid therapy, but also environment intervention and enough patient education. In addition to this new therapeutic strategy, we will describe about add-on effect of long-acting beta-2 agonists, theophylline, and leukotriene receptor antagonist.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Drug Therapy, Combination; Fluticasone; Glucocorticoids; Humans; Leukotriene Antagonists; Practice Guidelines as Topic; Theophylline

Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma.. To quantitatively assess the efficacy and safety of budesonide at different doses in order to establish whether a clinically significant dose response profile exists.. A search was carried out for Controlled and Randomised Clinical Trials (RCTs) using the Cochrane Airways Group trial register, correspondence with trial authors and the manufacturer.. Randomised trials in children and adults comparing one dose of budesonide to a second dose in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager.. 24 studies were selected for inclusion in the review (3907 subjects). In non-oral steroid treated, mild to moderately severe asthma no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma there was a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation with BUD 800 mcg/d compared to 200 mcg/d: RR 3.93 (95% CI, 1.4 to 10.9). This result was largely weighted by a single large high quality RCT. In a single study in patients receiving oral corticosteroids, clinically significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 and morning PEFR. In two studies there was no dose dependent oral steroid sparing effect for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d were apparent but the clinical significance of these findings is unclear.. Budesonide exhibits a clinically significant dose response effect for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

Inhaled budesonide is a widely used inhaled corticosteroid for asthma.. The objectives of this review was to compare the efficacy of budesonide with placebo in the treatment of chronic asthma.. The Cochrane Airways Group Trial Register and reference lists of articles was searched. We contacted trialists for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing budesonide to placebo in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data.. 43 studies met the inclusion criteria (2801 subjects). In non-oral steroid treated asthmatics, budesonide led to significant improvements in a number of measures of airway function. These included FEV1, Weighted Mean Difference (WMD) 3.7% predicted (95% CI 0.1, 7.2%); improvement in morning peak flow (PEF) from baseline WMD 29 L/min (95% CI 22, 36 L/min); improvement in evening PEF from baseline WMD 21 L/min (95% CI 13, 29 L/min). Varying methods of reporting symptoms limited the pooling of studies but all high methodological quality studies demonstrated significant improvements compared to placebo. Health status was not reported. Risk of trial withdrawal due to asthma exacerbation was lower with budesonide compared to placebo, relative risk 0.17 (95% CI 0.09, 0.33). Doses of 500-800 mcg/d appeared to have slightly larger effect sizes than lower doses, but no advantage for high doses were apparent. A single high quality RCT reported significant reductions in daily prednisolone requirement and the number of patients able to discontinue prednisolone completely in budesonide treated subjects compared to placebo. No difference in risk of oropharyngeal soreness/hoarseness or oral Candidiasis was apparent for budesonide compared to placebo. Long-term risk of adrenal insufficiency was not reported.. This review strongly supports use of budesonide in chronic asthma. Consensus guidelines for chronic asthma suggest titrating inhaled steroid dose to individual requirements. Evidence from this review of trials does not present a case for routine dose titration above 800 mcg/d.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Humans; Randomized Controlled Trials as Topic

Topics: Adrenergic beta-Antagonists; Aerosols; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Humans; Infant; Nebulizers and Vaporizers; Respiratory Therapy

Inhaled glucocorticoids (IGs) are today the first-line treatment for bronchial asthma. The systemic effects of inhaled glucocorticoids, such as suppressing the hypothalamic-pituitary-adrenal axis, are generally less than those with oral glucocorticoids. However, there is a long-term risk of adverse effects on bone. The objective of this piece was to review the published data on the effects of IGs on bone metabolism markers and bone mineral density in adults and in pediatric patients. The reviewed studies do not provide uniform results. Nevertheless, in general they suggest that IGs can affect metabolism and bone mineral density, especially: 1) when high doses are administered (more than 400 micrograms/day in children and more than 800 micrograms/day in adults), 2) in pediatric patients, in whom growth in stature can also be affected, 3) in patients whose intake of calcium and vitamin D is inadequate, and 4) in postmenopausal women not undergoing hormone replacement therapy. In general, at therapeutically equivalent doses, beclomethasone has a greater deleterious effect on bone than does budesonide, which in turn has more of an effect than does fluticasone. In addition to the obvious precaution of using the lowest effective dose, other proposed preventive measures include: 1) adequate instruction on the use of aerosols, 2) the use of large volume spacer devices, 3) rinsing the mouth after administering IGs, and 4) dietary adjustments or supplements in order to ensure an adequate intake of calcium and vitamin D.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Age Factors; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Female; Glucocorticoids; Humans; Infant; Middle Aged; Time Factors

To determine whether inhaled steroid therapy causes delayed linear growth in children with asthma.. Medline (1966-1998), Embase (1980-1998), and Cinahl (1982-1998) databases and bibliographies of included studies were searched for randomized, controlled trials of inhaled steroid therapy in children with asthma that evaluated linear growth.. Studies were included if they met the following criteria: subjects 0 to 18 years of age with the clinical diagnosis of asthma; subjects randomized to inhaled beclomethasone, budesonide, flunisolide, fluticasone, or triamcinolone versus a nonsteroidal inhaled control for a minimum of 3 months; single- or double-blind; and outcome convertible to linear growth velocity. English- and non-English-language trials were included.. Data were extracted using a priori guidelines. Methodologic quality was assessed independently by both authors. Outcome was extracted as linear growth velocity.. Included trials were subgrouped by inhaled steroid. The beclomethasone subgroup, with 4 studies and 450 subjects, showed a decrease in linear growth velocity of 1.51 cm/year (95% confidence interval: 1.15,1.87). The fluticasone subgroup, with 1 study and 183 subjects, showed a decrease in linear growth velocity of.43 cm/year (95% confidence interval:.01,.85). Sensitivity analysis in the beclomethasone subgroup, which evaluated study quality, mode of medication delivery, control medication, and statistical model, showed similar results.. This meta-analysis suggests that moderate doses of beclomethasone and fluticasone in children with mild to moderate asthma cause a decrease in linear growth velocity of 1.51 cm/year and.43 cm/year, respectively. The effects of inhaled steroids when given for >54 weeks, or on final adult height, remain unknown.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Humans; Infant; Infant, Newborn; Steroids; Triamcinolone

Topics: Administration, Topical; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Clinical Trials as Topic; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Nebulizers and Vaporizers

Topics: Adenoviridae Infections; Adenoviruses, Human; Administration, Topical; Animals; Anti-Inflammatory Agents; Asthma; Bronchiolitis; Budesonide; Disease Models, Animal; Drug Resistance; Glucocorticoids; Humans; Respiratory Tract Infections; Virus Diseases

Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which beta2-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension < or =8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchiolitis; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Croup; Drug Delivery Systems; Female; Humans; Infant; Infant, Newborn; Lung Diseases, Obstructive; Male; Middle Aged

The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens.. This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer.. This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF).. The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost-efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of > or = 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode-free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered.. Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Cost-Benefit Analysis; Fluticasone; Humans

Topics: Asthma; Budesonide; Child; Chronic Disease; Cyclosporine; Drug Administration Routes; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Leukotriene Antagonists; Methotrexate; Patient Compliance; Patient Education as Topic; Terbutaline; Treatment Failure

To appraise the data on systemic adverse effects of inhaled corticosteroids.. A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies.. Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression.. All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Budesonide; Dose-Response Relationship, Drug; Eye; Fluticasone; Glucocorticoids; Growth; Humans; Prednisolone; Skin; Triamcinolone

Current evidence suggests that addition of the long-acting beta2-agonist salmeterol to an inhaled corticosteroid in patients with persistent asthma symptoms provides greater clinical benefit than doubling the dosage of the inhaled corticosteroid. Fixed combination salmeterol/fluticasone propionate in 3 different fluticasone propionate dosage strengths administered via the Diskus powder inhaler does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles - including the influence of the corticosteroid on plasma cortisol levels. Administration of fixed combination salmeterol/ fluticasone propionate to both adults and children with persistent asthma provides greater improvements in lung function than either agent alone, and at least equal effectiveness to the same dosages of the 2 agents given by separate powder inhalers. Preliminary reports indicate that combination therapy has also demonstrated superior efficacy to budesonide (fluticasone propionate dosages were 25% those of budesonide). The most commonly encountered adverse effects in clinical trials with combined salmeterol/fluticasone propionate therapy have been oropharyngeal candidiasis. hoarseness/dysphonia, throat irritation, headache, tachycardia/palpitations, tremor and dizziness (all in < or =5% of patients).

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Clinical Trials as Topic; Drug Combinations; Fluticasone; Humans; Hydrocortisone; Nebulizers and Vaporizers; Salmeterol Xinafoate

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Budesonide; Fluticasone; Humans; Hydrocortisone

Underutilization of anti-inflammatory agents in the treatment of asthma has received widespread attention. Inhaled glucocorticosteroids are important agents for the management of asthma in children and adults. Budesonide has a high ratio of topical anti-inflammatory to systemic activity and is one of the most extensively used inhaled glucocorticoids. Budesonide inhalation suspension is the first formulation designed to deliver budesonide by way of nebulization for infants and children under 8 years of age with persistent asthma. Budesonide decreases airway hyperresponsiveness and reduces the number of inflammatory cells and mediators present in the airways of patients with asthma. Budesonide appears to be retained within cells, allowing for a once-daily treatment regimen in certain patient groups. After inhalation of nebulized budesonide, absorption is rapid. Data suggest that plasma concentrations of budesonide are similar in adults and children after inhalation of the same nominal dose from a nebulizer. In children 3 to 6 years of age, total systemic availability of budesonide after dosing with a jet nebulizer was approximately 6% of the labeled dose. Budesonide is highly protein bound, undergoes extensive first-pass hepatic metabolism, is metabolized by the liver cytochrome P450 system, and is primarily excreted in the urine as metabolites. In children 3 to 6 years of age, the volume of distribution at steady state of budesonide inhalation suspension is approximately 3 L/kg, with a terminal elimination half-life of 2.3 hours; systemic clearance is approximately 30 mL/kg. The pharmacodynamic and pharmacokinetic properties of budesonide inhalation suspension allow for potent local anti-inflammatory activity with limited systemic exposure.

Topics: Administration, Inhalation; Animals; Anti-Asthmatic Agents; Asthma; Budesonide; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

To present value of cost effectiveness evaluation in asthma treatment Material and methods. Meta-analysis of asthma treatment studies compared with data from National Healthcare Plan in Slovenia.. Patients treated with fluticasone propionate (FP) were successfully controlled for 41.7% of treated weeks compared with 34.1% in the group treated with budesonide (B) (p < 0.001). Purchase price for FP (1.524 SIT/week) is not significantly different from B (1.462 SIT/week). The overall mean weekly cost per patient was 3.077 SIT for patient treated with B and 1.916 SIT for patient treated with FP. Cost of health care contacts were 56 SIT in the FP group and 1.275 SIT in B group per week. The total expenditure per week of successful treatment would be 4.594 SIT/week in the FP group and 9.025 SIT/week in patients treated with B.. It is evident that by evaluation of purchase price only no final conclusion of cost effectiveness of treatment of asthma is possible.. Limited resources in the health care could be properly distributed only after carefully weighting costs and comparing outcomes.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Fluticasone; Humans; Slovenia

During therapy with inhaled corticosteroids (ICS) of asthmatic children studies examining growth over several weeks using a knemometer showed a dose-dependent reduction of lower leg growth. During maintenance treatment with beclomethasone 400 micrograms/day for several months the growth of asthmatic children was reduced by approximately 1 cm/year compared with contemporaries who had not been treated with this substance. No such growth retardation was found in studies on long-term therapy with budesonide (400-800 micrograms/day) or fluticasone (100-200 micrograms/day). However, differences between ICS are difficult to establish or to exclude, since the systemic availability may vary, due for instance to the properties of the inhaler and the individual inhaling technique. It appears that most children with asthma treated with ICS perform a catch-up growth so that they reach a normal height as young adults. Since growth retardation if any mostly occurs during the first three months of the treatment, growth of asthmatic children must be monitored carefully. When growth is reduced by > 0.25 standard deviation score within 1 year, the use of ICS needs to be reconsidered. This decision can best be made by a paediatrician or after consulting one.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Dose-Response Relationship, Drug; Fluticasone; Humans

Inhaled corticosteroids are the treatment of choice for asthma. However, poor compliance by patients is one of the principal difficulties forced by clinicians. Thus, it seems important to propose the minimal daily number of doses. This study has compared the various modes of administration of inhaler corticosteroids and was carried out in patients with mild to moderate persistent asthma. Thus, comparing two to four doses per day shows an identical efficacy if the dose is less than 800 micrograms per day. At higher doses only two studies have been carried out and there are discordant results. The studies compare two doses versus one single dose per day and equally disagree with numerous works in favor of a single daily dose. In the single study carried out for at least twelve months the twice daily dose was the most effective. Thus it seems reasonable to suggest a single dose for mild persistent asthmatics. For moderate persistent asthmatics the choice between a single or twice daily dose would depend on the therapeutic compliance of the patient.

Topics: Administration, Inhalation; Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Fluocinolone Acetonide; Humans; Placebos; Randomized Controlled Trials as Topic; Time Factors; Triamcinolone Acetonide

Despite the established efficacy of inhaled corticosteroids in improving lung function in asthma, there has not been a corresponding improvement in morbidity and mortality associated with the disease, which, in part, may result from non-compliance with the prescribed regimen. The reasons for this are many and varied, but an important measure in improving the level of compliance in asthma patients is simplification of the treatment regimen, which may be achieved by reducing the dose frequency and improving the ease of administration. In clinical trials designed to determine whether a reduction in dose frequency to once daily is associated with similar efficacy to that with more frequent administration, a number of studies have shown that once-daily administration of inhaled corticosteroids in both adults and children is as effective in controlling asthma as twice-daily administration of the same dosage, both when given as initial therapy in corticosteroid-naïve patients and in patients already receiving an inhaled corticosteroid. The drug for which most evidence to support a dosage change from twice-daily to once-daily therapy currently exists is budesonide, though limited evidence with other inhaled corticosteroids such as beclomethasone dipropionate, fluticasone propionate and flunisolide also supports once-daily use. Despite the larger single dosage with once-daily budesonide therapy, there has been no evidence in clinical trials of a greater incidence of local adverse effects such as hoarseness, throat irritation or oropharyngeal candidosis, and no evidence of adrenal suppression or growth retardation. Since compliance is an important factor that can affect the success or failure of asthma therapy, a reduction in the frequency of administration to once daily offers the potential advantage of improved compliance with treatment and hence better control of asthma. In the short term clinical trials conducted to date, patient preferences have favoured the once-daily regimen over twice-daily administration. When combined with other (e.g. educational) measures to improve patient compliance, a switch from twice-daily (or more frequent) administration to once-daily inhaled corticosteroid therapy seems likely to be beneficial in improving the long term outcome of treatment.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Humans; Patient Acceptance of Health Care; Patient Compliance

Topics: Allergens; Analgesics; Asthma; Bronchodilator Agents; Budesonide; Humans; Leukotriene Antagonists; Prostaglandin-Endoperoxide Synthases; Respiratory Therapy

The relative clinical efficacy and systemic effects of different inhaled corticosteroids is controversial. To obtain further information on this matter, the authors have performed meta-analysis of seven trials comparing fluticasone propionate (FP) with budesonide (Bud), and seven trials comparing FP with beclomethasone dipropionate (BDP) for the treatment of asthma of all severities in adult and paediatric patients. In all cases, the drugs were compared at clinically equivalent doses, i.e. FP was given at half (or less) the microgram dose. The total number of patients was 1980 (1000 treated with FP 200-800 micrograms day-1 and 980 with Bud 400-1600 micrograms day-1), and 1584 patients in the second analysis (780 treated with FP 200-1000 micrograms day-1 and 804 with BDP 400-2000 micrograms day-1). FP significantly improved mean morning peak expiratory flow rate (PEFR) compared with Bud, with an overall difference of +11 l min-1. Analysis of serum cortisols showed no differences between FP and Bud treatment at low doses, but at higher dosages, and overall, significant differences in favour of FP were observed. In the second meta-analysis, no significant differences in PEFR were observed between FP and BDP in any of the seven individual studies or in the pooled analysis. Analysis of serum cortisols showed a similar trend to the previous analysis, however, no overall difference in serum cortisol results were seen between FP and BDP. In conclusion, the pooled analysis shows that FP at half the dose (or less) is more effective than Bud and as effective as BDP in improving PEFR; in addition, these improvements were achieved with a reduction in cortisol suppression compared with BUD and with no greater degree of cortisol suppression compared with BDP. This demonstrates, in patients with asthma, that FP has an improved efficacy to safety ratio compared with older inhaled corticosteroids.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone; Peak Expiratory Flow Rate

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate

The physicochemical and pharmacokinetic characteristics of BDP and budesonide are somewhat different, but the overall result is that both are well suited for use as inhaled corticosteroids. Both BDP and budesonide are metabolized primarily by the liver, with one of the metabolites of BDP, 17-BMP, having greater receptor affinity than either the parent compound or budesonide, which has no active metabolites. BDP has a lower water solubility than either 17-BMP or budesonide, which have similar water solubilities. Budesonide has lower oral bioavailability than BDP; however, it is generally reported to have a longer plasma half-life than either BDP or 17-BMP. The physicochemical and pharmacokinetic profiles of inhaled BDP and budesonide provide both compounds with a favourable ratio of topical to systemic effects and support their well-established role in the treatment of asthma. The device used to deliver an inhaled corticosteroid influences the lung deposition of the drug and selection of the device should be made with an understanding of the particular advantages and disadvantages of the device for each individual patient.

Topics: Absorption; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Drug Delivery Systems; Humans; Liver; Lung; Nebulizers and Vaporizers; Structure-Activity Relationship

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Drug Administration Schedule; Drug Delivery Systems; Humans; Randomized Controlled Trials as Topic

Topics: Administration, Inhalation; Adrenal Glands; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Cataract; Child; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic; Skin

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Glucocorticoids; Humans; Infant; Randomized Controlled Trials as Topic; Time Factors

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Bone and Bones; Bone Density; Budesonide; Child; Female; Humans; Male; Middle Aged; Osteocalcin

In addition to its bronchodilatory effects, theophylline has anti-inflammatory and immunomodulatory effects. Since theophylline and corticosteroids act via different molecular mechanisms, they may be used in combination. Two recently completed trials have demonstrated that with respect to asthma control the combination of inhaled steroid (400 - 800 microg/d) plus theophylline is at least as effective as doubling the dose of inhaled steroid in patients who remain symptomatic on a dosage of 400 - 800 microg daily.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Theophylline

Topics: Administration, Inhalation; Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Growth; Humans; Osteoporosis; Pregnenediones; Triamcinolone Acetonide

Topics: Absorption; Administration, Topical; Adolescent; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Infant; Practice Guidelines as Topic; Pregnenediones; Risk Factors

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Fluticasone; Humans; Pregnenediones; Risk Assessment

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Follow-Up Studies; Forced Expiratory Volume; Forecasting; Glucocorticoids; Humans; Lung Diseases, Obstructive; Peak Expiratory Flow Rate; Pregnenediones; Randomized Controlled Trials as Topic; Smoking; Vital Capacity

Bronchial asthma is characteristic of chronic airway inflammatory disorder which many inflammatory cells play a role, BDP therefore has become a basic drug (controller) in the treatment of asthma. Recently new dry powder inhalation systems of corticosteroid such as fluticasone propionate (Diskhaler) and budesonide (Turbuhaler) have been studied to examine the dose response clinical efficacy to BDP. Clinical efficacy of both drugs are equivocal to double dose of BDP. These excellent drugs will be soon available for clinical use in Japan.

Topics: Administration, Oral; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fluticasone; Humans; Japan; Nebulizers and Vaporizers; Powders; Pregnenediones

Inhalation corticosteroids (beclometasone dipropionate, budesonide, flunisolide) proved effective against bronchial asthma (BA) and safe as they induce no severe systemic side effects. Of these three drugs side effects arise most frequently in administration of beclometasone dipropionate, least frequently of flunisolide. These inhalation corticosteroids are indicated both in non-steroid-dependent and steroid-dependent BA to reduce the dose of oral steroids or, if possible, for their complete discontinuation. Flunisolide is the most potent and effective of all inhalation corticosteroids used in current practice.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Evaluation; Fluocinolone Acetonide; Humans; Pregnenediones; Prodrugs

Inhaled glucocorticosteroids have become the cornerstone mode of anti-inflammatory treatment in children, especially with bronchial asthma. Many publications document the clinical efficacy of inhaled steroids and an increasing number of authors point out the possible systemic effects of topical steroids, such as effects on growth, impaired bone metabolism and adrenal suppression. The goal of this review article is to summarize published data. The author stresses possible relevant side effects in relation to dose and inhalation technique and focuses on the most appropriate indications and therapeutic modalities of inhaled steroids. The article yields valuable information for both practitioners and clinicians which will assist them in administering inhaled steroids and in discussing questions of safety with medical professionals and laymen.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenal Cortex; Anti-Inflammatory Agents; Asthma; Bone and Bones; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Glucocorticoids; Growth; Humans; Infant; Pregnenediones

Budesonide is an inhaled corticosteroid that is used prophylactically to reduce the underlying inflammation and consequent airways narrowing associated with asthma. Widespread clinical experience has shown that inhaled budesonide is effective and well tolerated, and its use is well established in the management of adult and childhood asthma. In developed countries, asthma is a major health problem and consumes a large proportion of healthcare resources. Both the prevalence and severity of asthma appear to be increasing. Additionally, asthma-related mortality has been reported to have gradually increased since the mid- to late-1970s in many countries, possibly due to undertreatment and/or suboptimal management of the disease. Current guidelines recommend a shift away from initial treatment with oral bronchodilators, such as theophylline, or regular use of beta 2-agonist inhalers, toward the earlier use of more expensive inhalers containing corticosteroids. Inhaled bronchodilators are still used as indicated for treatment of acute attacks. Data suggest that the acquisition cost of budesonide is more than offset by decreased morbidity and reductions in costs associated with acute asthma exacerbations. Both once-daily administration and its administration in dry powder form via Turbuhaler appear to be well accepted by patients; these factors may potentially improve patient compliance with therapy. Budesonide appears to have positive effects on some quality-of-life indices, although studies using validated quality-of-life instruments are needed to confirm these conclusions. Modelling studies would be helpful in order to assess the possible economic benefits to society through reduction of the considerable direct and indirect costs of asthma and cost-effectiveness comparisons with other inhaled corticosteroids are needed to clarify its relative positioning in this regard. Until then, the available data provide an encouraging pharmacoeconomic rationale for budesonide as first-line asthma therapy, and a good basis for future pharmacoeconomic analysis of asthma management.

Topics: Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Economics, Pharmaceutical; Humans; Pregnenediones; Prospective Studies; Quality of Life

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Glucocorticoids; Growth; Humans; Longitudinal Studies; Osteoporosis; Pregnenediones

The present review summarized the state of our knowledge on glucocorticosteroids, their mechanisms of action, pharmacological effects, pharmacokinetics and adverse effects. Oral steroids are very effective in treatment of asthma, however, when given in more than low doses and for a prolonged time, they may have quite serious side effects. The pharmacology of inhaled steroids is described. New inhaled glucocorticosteroids like budesonide and flunisolide are readily absorbed from the airway mucosa into the blood but are rapidly biotransformed in the liver into au inactive metabolite. Obviously the greatly reduces the risk of systemic side effects that exist with older glucocorticosteroids, e.g. dexamethasone.

Topics: Asthma; Budesonide; Dexamethasone; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Glucocorticoids; Gonadal Steroid Hormones; Humans; Hydrocortisone; Liver; Pregnenediones

A wide range of topics can be covered when considering a review of respiratory therapeutics. This review focuses on advances and controversies in the therapy of asthma, including issues regarding medications such as inhaled beta 2-agonists, inhaled corticosteroids, cromolyn sodium, and theophylline. Bronchodilator therapy for acute viral bronchiolitis remains a controversial issue and is discussed in light of recent published manuscripts. Issues regarding surfactant therapy for respiratory distress syndrome remain prominent in the neonatal respiratory therapeutics literature and recent findings in this area are reported. Advances in the treatment of cystic fibrosis, as well as a review concerning the pulmonary toxicity of various medications used in the treatment of pediatric illness are discussed.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchiolitis, Viral; Bronchodilator Agents; Budesonide; Child; Cystic Fibrosis; Hemosiderosis; Humans; Infant, Newborn; Lung Diseases; Methotrexate; Pregnenediones; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Theophylline

Inhaled budesonide is now well established in the management of adult and childhood asthma, and when nebulised, shows considerable promise in recurrent wheezing and in severe asthma in infants. Studies conducted since the drug was previously reviewed in the Journal in 1984 have confirmed the comparable efficacy of equal doses of budesonide and beclomethasone dipropionate, the ability of budesonide to reduce oral maintenance corticosteroid requirements, and demonstrated its potential as first-line treatment of mild to moderate asthma. Recent studies have established the usefulness and good tolerability of intranasal budesonide in the treatment of seasonal allergic and perennial rhinitis where the drug is more effective than disodium cromoglycate and at least as effective as beclomethasone dipropionate. After up to 10 years of treatment with inhaled budesonide there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Inhaled corticosteroids continue to play an important role in the treatment of asthma with an increasing focus on their role as first-line therapy, and widespread clinical experience has shown budesonide is an effective and well tolerated member of this class which should be considered where inhaled or intranasal administration of a corticosteroid is indicated.

Topics: Aerosols; Asthma; Bronchodilator Agents; Budesonide; Glucocorticoids; Humans; Pregnenediones; Rhinitis

Owing to improvements made during the last 15 years in the pathophysiological and pharmacological research, many new corticosteroids have been successfully experimented. They have high activity on the target organ and they are suitable for long term therapies since they have not any systemic and/or local side effects. Nowadays the topical intranasal corticosteroid therapy is indispensable for allergic rhinitis treatment and it is very useful for many nasal and bronchopulmonary diseases (some chronic rhinitis, nasal polyposis, bronchial asthma, chronic obstructive bronchopulmonary diseases). The authors use their personal experience and carefully review the literature to describe the general aspects (pharmacology, pharmacokinetics, toxicology, side effects and contraindications) and to analyze the single drugs currently used in Italy and abroad. Finally, they compare the efficacy of each topical intranasal glucocorticoid among themselves and with other drugs.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Budesonide; Child; Fluocinolone Acetonide; Humans; Hydrocortisone; Lung Diseases, Obstructive; Pregnenediones; Rhinitis

Hyperresponsiveness of the bronchi is defined as an excessive reaction of bronchial mucosa to irritants that do no harm to a healthy mucosa. Measures to prevent bronchial hyperreactivity in children with asthma and other diseases remain rather ineffective at present. Though progress has been made in some areas.

Topics: Administration, Topical; Airway Resistance; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Combined Modality Therapy; Cromolyn Sodium; Drug Therapy, Combination; Glucocorticoids; Humans; Pregnenediones; Respiratory Hypersensitivity; Respiratory Tract Infections; Risk Factors

Topics: Administration, Inhalation; Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Glucocorticoids; Humans; Pregnenediones

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Betamethasone; Budesonide; Drug Administration Schedule; Fluocinolone Acetonide; Humans; Pregnenediones; Triamcinolone Acetonide

Topics: Acute Disease; Aminophylline; Aspirin; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Calcium Channel Blockers; Cromolyn Sodium; Humans; Parasympatholytics; Pregnenediones; Rifampin; Theophylline

Topically active inhaled corticosteroid (IC) drugs are highly effective for chronic asthma. Formalized conceptions of "high, low or safe" dosages of these drugs may be less appropriate than one of "optimal dosage". It seems reasonable to formulate a specific goal of treatment, and then fit dosage to the individual needs and tolerances of the patient rather than to a conventionalized "safe" limit, based on averaged data from different and perhaps quite dissimilar subjects. The studies reviewed here illustrate some principles applicable to the effective use of IC drugs.

Topics: Aerosols; Asthma; Beclomethasone; Budesonide; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Glossitis; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Prednisone; Pregnenediones; Respiratory Therapy; Risk; Time Factors; Voice Disorders

Budesonide is a non-halogenated glucocorticosteroid which has been shown to possess a high ratio of topical to systemic activity compared with a number of reference corticosteroids such as beclomethasone dipropionate, flunisolide, and triamcinolone acetonide. It appears to undergo extensive first-pass metabolism to metabolites of minimal activity which accounts for the low level of systemic activity. The majority of therapeutic trials in asthma have been of short term duration and have demonstrated that conventional doses of inhaled budesonide (200 to 800 micrograms/day) and beclomethasone dipropionate (400 to 800 micrograms/day) are of similar efficacy in both adults and children with moderate to severe asthma. Other studies have compared high doses of inhaled budesonide (400 to 3200 micrograms/day in 4 divided doses) with both alternate day (7.5 to 60 mg) and daily (7.5 to 40 mg) oral prednisone in patients with severe or unstable asthma. In the small number of such trials to date, inhaled budesonide was superior to prednisone with respect to the level of asthma control and the lesser influence on adrenal function. Long term open studies have similarly shown that inhaled budesonide can be gradually substituted for oral prednisone in steroid-dependent patients, often with a concomitant improvement in pulmonary function and asthma control. Intranasal budesonide (200 to 400 micrograms/day) relieves nasal symptoms in patients with seasonal allergic, perennial allergic and vasomotor rhinitis. In comparative studies in patients with seasonal rhinitis it has been shown to be of similar efficacy as intranasal flunisolide and intranasal beclomethasone dipropionate and superior to intranasal sodium cromoglycate (cromolyn sodium) and the antihistamine dexchlorpheniramine. Following inhalation, the most commonly reported side effects have been candidiasis, dysphonia and sore throat, while after intranasal administration the most frequent adverse reactions have been nasal stinging, throat irritation, dry nose and slight nasal bleeding. At usual dosages, both formulations of budesonide appear to have little or no effect on adrenal function. Thus, at this stage in its development budesonide has been shown to offer an effective alternative to oral or other inhaled corticosteroids in the management of asthma and rhinitis. However, its relative efficacy and tolerability during long term use, compared with beclomethasone dipropionate, remains to be clarified.

Topics: Administration, Topical; Adrenal Glands; Adult; Anaphylaxis; Animals; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Clinical Trials as Topic; Cricetinae; Glucocorticoids; Humans; Intestinal Absorption; Kinetics; Male; Pregnenediones; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Rhinitis, Vasomotor; Tissue Distribution

Bronchial asthma is a prevalent type of respiratory disease that affects a large proportion of pediatric patients. The purpose of this study is to further investigate the clinical effects of budesonide combined with montelukast sodium in treating bronchial asthma.. Eighty six children with bronchial asthma were equally divided into study and control groups via randomized double-blind controlled trial. The control group was treated with aerosol inhalation of budesonide combined with placebo, while the study group was treated with budesonide combined with montelukast sodium. Pulmonary function parameters, immunoglobulin, and recovery of related symptoms, along with the adverse reaction rate, were observed and compared between both groups.. Before treatment, there was no marked difference in pulmonary function parameters and immunoglobulin indexes between both groups (. Budesonide combined with montelukast sodium in the treatment of bronchial asthma has the value of clinical application and promotion.

Topics: Acetates; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Humans; Quinolines

To evaluate the clinical efficacy and safety of combining omalizumab with budesonide formoterol to treat children with moderate and severe allergic asthma, and investigate the effect of this combination therapy on pulmonary and immune functions.. The data of 88 children with moderate and severe allergic asthma, who were admitted to our hospital between July 2021 and July 2022, were included in the study. The patients were randomly assigned either to control group (n = 44; received budesonide formoterol inhalation therapy) or experimental group (n = 44; received omalizumab subcutaneous injection + budesonide formoterol inhalation therapy) using computer-generated randomization. The clinical efficacy, asthma control (measured using childhood Asthma-Control Test [C-ACT] score), pulmonary function (forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow), immune function (cluster of differentiation 3 cells [CD3. After treatment, the experimental group had improved levels of pulmonary function and immune function indexes, higher C-ACT scores, and a higher overall response rate than the control group (P < 0.05). In addition, the incidence of adverse reactions was not significantly different between both groups (P > 0.05).. The combination of omalizumab with budesonide formoterol for treating moderate and severe allergic asthma in children demonstrated promising clinical efficacy and improved their pulmonary and immune functions, leading to more rational asthma control. The combined regimen demonstrated satisfactory clinical safety and deserved clinical promotion.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Double-Blind Method; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Immunity; Omalizumab; Treatment Outcome

The aim of our study is to provide a novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms for preventing airway damage.. This single-center, prospective, randomized and standard treatment parallel control clinical trial recruited adult asthma patients. The patients were randomized into either the rescue intervention strategy (RIS) group or control group. The rescue intervention strategy for the RIS group included budesonide/formoterol plus the original treatment until the severe pollution ended. The control group was maintained on the original treatment. The follow-up observation period was 1 year.. A novel strategy to administer treatment at the first signs of severe air pollution and before patients experience symptoms may decrease the risk of asthma exacerbations and negative outcomes under severe air pollution conditions.. ChiCTR, ChiCTR1900026757. http://www.chictr.org.cn.

Topics: Administration, Inhalation; Adult; Air Pollution; Asthma; Bronchodilator Agents; Budesonide; Formoterol Fumarate; Humans; Prospective Studies

To study whether addition of pidotimod to inhaled corticosteroid (ICS) therapy enhances control in children with persistent asthma, as compared to ICS therapy alone.. Triple-blinded, randomized controlled trial.. Allergy and Asthma Clinic, Department of Pediatrics, at a tertiary care hospital between May, 2018 and June, 2019.. 79 children (5-12 years) with newly diagnosed persistent asthma as per Global Initiative for Asthma guidelines.. Children received 7 mL twice-a-day for 15 day, followed by 7 mL once-a-day for 45 days of either pidotimod (n=39) or placebo (n=40). In addition, both groups received inhaled budesonide via metered dose inhaler and spacer, throughout the study. Children were followed up every 4 weeks for a total of 12 weeks. At each follow-up visit, peak expiratory flow (PEF) and asthma symptom score and medicine adverse effects were recorded.. Change in PEF at 12 weeks compared to baseline. Secondary outcomes were PEF at each follow-up visit, asthma symptom score at each visit, change in asthma symptom score at 12 weeks, and adverse event profile.. The median (IQR) change in PEF (from baseline to 12 weeks) was 13.0% (0.8%, 28.3%) in pidotimod group (n=35) vs 17.7% (4.3%, 35.2%) in placebo group (n=35) (P=0.69). All the secondary outcomes were also comparable between the two groups. There were no significant adverse effects observed.. Addition of pidotimod for 8 weeks to standard ICS therapy did not enhance asthma control compared to placebo.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Child; Double-Blind Method; Humans; Metered Dose Inhalers; Pyrrolidonecarboxylic Acid; Thiazolidines

As-needed low-dose combination budesonide-formoterol is recommended by asthma guidelines in many countries as an alternative to maintenance inhaled corticosteroids (ICS) for treatment of mild asthma, but there are few data on patient attitudes toward these regimens. This study explored the comparative implementation experiences and future treatment preferences of mild asthma patients who had experienced these two treatment regimens.. A subgroup of adults randomised to maintenance ICS or as-needed ICS-formoterol in a multinational, 52-week open-label randomised controlled trial (NovelSTART) in mild asthma patients were interviewed to explore their motivations for treatment use during the study and their preferences for future treatment.. Semistructured interviews were conducted with 74 participants (Maintenance group: n=39, As-needed group n=35, mean age 38 (range 19-69)) and thematically analysed from transcribed audiorecordings.. Emergent themes from analysis comprised: 'How much my asthma affects me' (how their asthma's impact affected their self-management motivation); 'What I know about asthma' (limited knowledge impeded appropriate self-management decision making); 'How much effort this treatment regimen involves for me' (treatment complexity and/or difficulty establishing a medication routine impeded implementation, particularly in the Maintenance group); and 'My beliefs about the benefits and risks of this treatment' (patients who considered their treatment as ineffective, eg, limited difference in symptoms relative to salbutamol (both groups) or slower onset of relief (As-needed group) had poor motivation to use the treatment). Due to the simplicity of the as-needed combination strategy, this was the preferred future regimen, even by patients who had not yet tried it.. Key patient perspectives on the implementation of preventer treatments for mild asthma included factors relating to perceived asthma burden, disease knowledge, treatment complexity and treatment usefulness or safety. The as-needed budesonide-formoterol regimen was preferred to maintenance ICS treatment in mild asthma though patient education is urgently needed to address implementation motivation.. ACTRN12615000999538.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Humans

Allergic Rhinitis (AR) is a prevalent chronic inflammatory nasal condition with significant negative effects on the patients' quality of life. This study aimed to investigate the efficacy of Montelukast and intranasal antihistamine in combination with intranasal corticosteroid (INCS) in moderate to severe allergic rhinitis on the patients' quality of life and AR control.. This double-blind randomized clinical trial study was carried out on 66 moderate to severe AR patients referred to Namazi Hospital, Shiraz, Iran from 2020 to 2021, who were randomly divided into 3 groups. Group one received Montelukast add-on therapy and Budesonide nasal spray. The second group received intranasal antihistamine (Azelastine) add-on therapy and Budesonide nasal spray and the third group as the control group received intranasal Budesonide spray with a placebo tablet.To measure the impact of each medication on the patient's quality of life and AR control, we employed the Sino-Nasal Outcome Test-22 questionnaire (SNOT 22). We evaluated the symptoms and compared them at baseline, one and three months after the start of treatments. Spirometry was performed to investigate the possibility of co-morbid asthma at baseline and end of the study.. The patients' mean age was 30.13 ± 12.7 years. Most patients experienced perennial AR (65.2%). Reduction of mean scores SNOT22 was statistically different between groups (P-value < 0.001). Three months after treatment, the mean decrease of SNOT-22 in the Azelastine group was statistically significant compared to both Montelukast (P-value < 0.001) and control groups (P-value < 0.001). No significant difference was observed between the Montelukast and control groups (P-value = 0.142). 23 of 66 patients were diagnosed with asthma and asthma treatment was initiated. The amount of FEV1 change after AR treatment was not statistically significant between the groups in asthmatic patients (P-value = 0.351).. Based on our findings, we recommend Azelastine in conjunction with an intranasal corticosteroid for the treatment of moderate to severe allergic rhinitis. In moderate to severe AR or even asthma management, Montelukast has no greater impact than INCS.

Topics: Acetates; Administration, Intranasal; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Cyclopropanes; Double-Blind Method; Histamine Antagonists; Histamine H1 Antagonists; Humans; Nasal Sprays; Phthalazines; Quality of Life; Quinolines; Rhinitis, Allergic; Sulfides; Treatment Outcome; Young Adult

There are limited options for treatment of the common disease, equine asthma. The aim of this study was to estimate the feasibility and potential efficacy of using nebulized lidocaine for treating equine asthma, while at the same time treating a separate cohort of asthmatic horses with inhaled budesonide. Nineteen horses with a history consistent with equine asthma were recruited from our referral population for a double-blind, randomized, controlled pilot clinical trial using Consolidated Standards of Reporting Trials (CONSORT) guidelines. After screening, 16 horses met the inclusion criteria for equine asthma and 13 horses actually completed the study. Horses were treated by their owners at home for 14 d before returning to our hospital for follow-up assessment. Interventions consisted of nebulization q12h for 14 d with 1.0 mg/kg body weight (BW) of lidocaine or corticosteroid treatment (nebulized budesonide 1 μg/kg, q12h). Clinical and tracheal mucus score, pulmonary function testing, and respiratory secretion cytology were assessed after 2 weeks of treatment to determine the outcome. Both lidocaine and budesonide cohorts had significant decreases (. Il existe des options limitées pour le traitement de la maladie répandue, l’asthme équin. Le but de cette étude était d’estimer la faisabilité et l’efficacité potentielle de l’utilisation de la lidocaïne nébulisée pour traiter l’asthme équin, tout en traitant en même temps une cohorte distincte de chevaux asthmatiques avec du budésonide inhalé. Dix-neuf chevaux ayant des antécédents compatibles avec l’asthme équin ont été recrutés dans notre population de référence pour un essai clinique pilote contrôlé, randomisé, en double aveugle, conformément aux directives CONSORT (

Topics: Administration, Inhalation; Animals; Asthma; Bronchoalveolar Lavage; Budesonide; Double-Blind Method; Horse Diseases; Horses; Lidocaine

As asthma symptoms worsen, patients typically rely on short-acting β. We conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol-budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two actuations of 90 μg and 80 μg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 μg of albuterol and 80 μg of budesonide (with each dose consisting of two actuations of 90 μg and 40 μg, respectively [the lower-dose combination group]), or 180 μg of albuterol (with each dose consisting of two actuations of 90 μg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population.. A total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P = 0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P = 0.052). The incidence of adverse events was similar in the three trial groups.. The risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies. (Funded by Avillion; MANDALA ClinicalTrials.gov number, NCT03769090.).

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Maintenance Chemotherapy; Nebulizers and Vaporizers; Symptom Flare Up; Young Adult

While the safety and efficacy of inhaled budesonide-formoterol, used as-needed for symptoms, has been established for patients with asthma, it has not been trialed in undifferentiated patients with chronic respiratory diseases. We aimed to assess the feasibility of a pragmatic intervention that entails a stepped algorithm using inhaled budesonide-formoterol (dry powder inhaler, 160μg/4.5μg per dose) for patients presenting with chronic respiratory diseases to three rural district hospitals in Hanoi, Vietnam.. We recruited patients with evidence of airflow obstruction on spirometry and/or symptoms consistent with asthma. The algorithm consisted of three steps: 1. as-needed inhaled budesonide-formoterol for symptoms, 2. maintenance plus as-needed inhaled budesonide-formoterol, and 3. referral to a higher-level healthcare facility. All participants started at step 1, with escalation to the next step at review visits if there had been exacerbation(s) or inadequate symptom control. Patients were followed for 12 months.. Among 313 participants who started the treatment algorithm, 47.2% had ≥ 1 episode of acute respiratory symptoms requiring a visit to hospital or clinic and 35.4% were diagnosed with an exacerbation. Twelve months after enrolment, 50.7% still adhered to inhaled budesonide-formoterol at the recommended treatment step. The mean and median number of doses per day was 1.5 (standard deviation 1.2) doses and 1.3 (interquartile range 0.7-2.3) doses, respectively. The proportion of patients taking more than 800μg budesonide per day was 3.8%.. This novel therapeutic algorithm is feasible for patients with chronic respiratory diseases in a rural setting in Vietnam. Further studies are required to establish the effectiveness, safety and cost-effectiveness of similar approaches in different settings.. ACTRN12619000554167.

Topics: Administration, Inhalation; Algorithms; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Respiration Disorders; Treatment Outcome

The additive benefit of inhaled corticosteroid when used with systemic corticosteroid in acute asthma is still unclear. The objective of this study was to assess the effect of high and repeated doses of inhaled budesonide when combined with the standard treatment of adult acute asthma.. It was a prospective double-blind randomized controlled study performed in the emergency department (ED) from May 1, 2010 to February 28, 2011 (ClinicalTrials.gov, NCT04016220). Fifty patients were included and were randomized to receive intravenous hydrocortisone hemisuccinate in association with nebulized budesonide (n = 23, budesonide group) or normal saline (n = 27, control group). Nebulization of budesonide or saline was done in combination with 5 mg of terbutaline every 20 min the first hour, then at 2 h (H2), and 3 h (H3). All patients received standard treatment. Efficacy and safety of inhaled budesonide were evaluated every 30 min for 180 min.. A significant increase in peak expiratory flow (PEF) was observed in both treatment groups at evaluation times. The increase in PEF persisted significantly compared to the previous measurement in both groups. There was no significant difference in the PEF between the two groups at evaluation times. There was no significant difference between the two groups in the evolution in the respiratory rate and heart rate. There was also no statistically significant difference between the two groups in the rate of hospitalization, the discharge criteria before the end of the protocol.. Considering its limited power, our study suggests that the association of nebulized budesonide with hydrocortisone hemisuccinate has no additional effect over the use of hydrocortisone alone in adults' acute asthma managed in the ED.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Double-Blind Method; Emergency Service, Hospital; Humans; Prospective Studies

Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.. Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.. Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Antitussive Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Capsaicin; Cough; Cyclopropanes; Formoterol Fumarate; Humans; Inflammation; Leukotriene Antagonists; Quinolines; Sulfides

To explore and compare the clinical control of three atomized inhalation budesonide (BUD) regimens for Chinese preschool children with recurrent wheezing using Test for Respiratory and Asthma Control (TRACK) scores. A total of 474 preschool children with positive Modified Asthma Predictive Index (mAPI) were randomly assigned to a daily group (initially given inhaled BUD 1 mg once a day and assessed every 4 weeks; if symptom were well controlled for 12 weeks, the dose was reduced to 25-50% of the previous dose until afinal dose of 0.25 mg once a day, maintained until 52 weeks), an intermittent high-dose group (1 mg twice daily for 7 days starting early during a predefined respiratory tract illness) and an intermittent medium-dose group (0.5 mg twice daily as soon as they contacted allergens or experienced nasal congestion, a runny nose, cough or other suspicious respiratory symptoms and continuing until symptoms were reduced or risk factors were absent for 3 days) for 52 weeks of treatment. The TRACK questionnaire was administered every 4 weeks. When TRACK scores were ≥ 80, symptoms were considered to be controlled. The average TRACK scores of the three groups after treatment were significantly higher than those before treatment (P < 0.001). There were no significant differences in the average TRACK scores and control rate after treatment at every 4 weeks in the three groups (P > 0.05). Te number of systemic glucocorticoid courses, urgent care visits for wheezing, and wheezing episodes before and after treatment were significantly different within each of the three groups (P < 0.001), but not among the three groups (P > 0.05). In clinical treatment of children, one of the three treatment options can be selected according to the specific situation case of mAPI- positive recurrent wheezing children.

Topics: Administration, Inhalation; Asthma; Budesonide; Child, Preschool; China; Glucocorticoids; Humans; Respiratory Sounds

While mild asthma is generally better controlled than more severe disease, patients with mild asthma may experience severe exacerbations. Definite differences between countries in terms of asthma severity and control were described previously. Since SYGMA was a global study, this sub-analysis was conducted in geographic region to investigate potential regional specificities.. The SYGMA2 trial is double-blind multicenter study involving patients ≥12 years of age with mild asthma (. The Russian population of patients with mild asthma hardly differs from the population in other countries in terms of baseline demographic and anthropometric characteristics, smoking status, and duration of asthma. At the study entry few patients from Russia received maintenance therapy with ICS and had symptom control, but the majority was uncontrolled on short-acting bronchodilators, thus the uncontrolled/controlled ratio was 52%/48% vs 45%/55% in other countries. More patients with mild asthma in the Russian group had faced at least one severe exacerbation in the previous year (30.1% vs 20.7%).. The subanalysis revealed a delayed prescription of controller (ICS) therapy and overuse of short-acting bronchodilators in the Russian population with mild asthma. These factors can lead to insufficient symptom control and higher risk of severe exacerbation in the Russian population with mild asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Humans; Retrospective Studies

To compare median change in morning peak expiratory flow rate (PEFR) and clinical asthma control in children receiving total daily dosage of inhaled budesonide administered either as once-daily or divided twice-daily dose.. It was a randomized, parallel group, open label, noninferiority trial on 80 children aged 5-12 y with mild or moderate well-controlled asthma. Baseline parameters were recorded and subjects received inhaled budesonide either as once-daily or divided twice-daily dose. Primary outcome was median change in morning PEFR. Secondary outcomes included median change in evening and diurnal variation in PEFR, asthma symptom control as per Global Initiative for Asthma, 2017 and Asthma Control Questionnaire, and spirometric measurements taken at the clinic.. The median [interquartile range (IQR)] increase in morning PEFR was more in children receiving once-daily as compared to those receiving twice-daily inhaled budesonide (by 6:00 L/min; IQR: -44.00-63.00 L/min vs. 4:00 L/min; IQR: -67.50-67.50 L/min, p 0.222; 95% CI: -1.37 to 19.08). Other spirometric variables and symptoms scores were also nonsignificant except median change in evening PEFR which was in favor of twice-daily regimen.. Once-daily administration of inhaled budesonide is noninferior to twice-daily administration of equivalent daily dosage of inhaled budesonide.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Forced Expiratory Volume; Humans; Peak Expiratory Flow Rate

Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta. The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.. NCT03769090.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans

To evaluate the effect of nebulized budesonide plus salbutamol on mild to moderate acute exacerbation of asthma in children in comparison with nebulized salbutamol alone.. A comparative clinical study was conducted in Karbala Teaching Hospital, for children from January 2016 to January 2017 on patients aged 1 to 12 years who presented to emergency department (ED) with mild to moderate asthma exacerbation. One hundred patients with mild to moderate acute asthma had been interviewed in the ED using a specific questionnaire designed for the study. Baseline pulmonary index score (PIS) had been done for each patient then patients were randomly allocated into two groups; group A- Salbutamol group (50 patients) and group B- Budesonide plus Salbutamol group (50 patients). PIS had been measured for each patient every 30 minutes (at baseline, 30, 60, 90 minutes), and their fate had been determined whether discharged from hospital or continue the treatment according to PIS.. After 30, 60 and 90 minutes both patients treated with budesonide plus salbutamol and salbutamol monotherapy showed a significant reduction in PIS (p<0.05) as compared with their baseline score. After 30 minutes from ED admission, patients treated with a combination of budesonide plus salbutamol had significantly lower PISs (5.96±2.23) than those treated with salbutamol alone (7.32±2.18). At the end of 90 minutes, there were 28 (56 %) remaining patients in the ED from the salbutamol group and only 14 (28 %) patients from the combination group with a significant difference in the number of patients between groups (p<0.05). The mean duration of stay in ED had been significantly shorter in patients treated with nebulized budesonide plus salbutamol (p<0.05).. Treatment of asthmatic children having mild to moderate acute exacerbation with a combination of nebulized budesonide plus salbutamol resulted in significant clinical improvement and reduction in the duration of emergency department stay compared to children on nebulized salbutamol monotherapy.

Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Humans; Infant; Nebulizers and Vaporizers

Acute exacerbations contribute significantly to the morbidity of asthma. Recent studies have shown that early detection and treatment of asthma exacerbations leads to improved outcomes. We aimed to develop a machine learning algorithm to detect severe asthma exacerbations using easily available daily monitoring data.. We analyzed daily peak expiratory flow and symptom scores recorded by participants in the SAKURA study (NCT00839800), an international multicentre randomized controlled trial comparing budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline as reliever, in adults with persistent asthma. The dataset consisted of 728,535 records of daily monitoring data in 2010 patients, with 576 severe exacerbation events. Data post-processing techniques included normalization, standardization, calculation of differences or slopes over time and the use of smoothing filters. Principal components analysis was used to reduce the large number of derived variables to a smaller number of linearly independent components. Logistic regression, decision tree, naïve Bayes, and perceptron algorithms were evaluated. Model accuracy was assessed using stratified cross-validation. The primary outcome was the detection of exacerbations on the same day or up to three days in the future.. The best model used logistic regression with input variables derived from post-processed data using principal components analysis. This had an area under the receiver operating characteristic curve of 0.85, with a sensitivity of 90% and specificity of 83% for severe asthma exacerbations.. Asthma exacerbations may be detected using machine learning algorithms applied to daily self-monitoring of peak expiratory flow and asthma symptoms.

Topics: Asthma; Bronchodilator Agents; Budesonide; Disease Progression; Drug Combinations; Female; Formoterol Fumarate; Home Care Services; Humans; Machine Learning; Male; Middle Aged; Monitoring, Physiologic; Severity of Illness Index; Terbutaline

In mild asthma, as-needed budesonide-formoterol reduces long-term exacerbation risk compared with as-needed short-acting β. SYGMA 1 was a 52-week, double-blind, randomised, controlled, phase 3 trial, in which patients aged 12 years or older with mild asthma were randomly assigned (1:1:1) to placebo twice daily plus as-needed terbutaline 0·5 mg, placebo twice daily plus as-needed budesonide-formoterol 200-6 μg, or budesonide 200 μg twice daily plus as-needed terbutaline (ie, budesonide maintenance group). In this post-hoc analysis, we assessed the frequency of reliever use and the risk of a severe exacerbation in the 21 days after first use of more than two, four, six, or eight reliever inhalations in 24 h. SYGMA 1 is registered with ClinicalTrials.gov, NCT02149199, and is now complete.. Of 5721 patients enrolled in SYGMA 1, 3849 were randomly assigned to as-needed terbutaline (n=1280), as-needed budesonide-formoterol (n=1279), or budesonide maintenance (n=1290), of whom 3836 had evaluable data (n=1277 as-needed terbutaline, n=1277 as needed budesonide-formoterol, and n=1282 budesonide maintenance). Median reliever use was 0·32 (IQR 0·08-0·91) inhalations per day for the as-needed terbutaline group, 0·29 (0·07-0·72) for the as-needed budesonide-formoterol group, and 0·16 (0·04-0·52) for the budesonide maintenance group. Compared with as-needed terbutaline, after adjustment for age, sex, randomly assigned treatment, pre-study treatment group, baseline % predicted post-bronchodilator FEV. In mild asthma, as-needed budesonide-formoterol reduces the short-term risk of severe exacerbations after a single day of higher use (more than two as-needed inhalations), even when overall use is infrequent. Use of an anti-inflammatory reliever might reduce the risk of short-term severe exacerbations by the timely provision of increased doses of as-needed inhaled corticosteroids and formoterol when symptoms occur. These findings should be further assessed in prospective randomised clinical trials.. AstraZeneca.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Formoterol Fumarate; Humans; Male; Severity of Illness Index; Treatment Outcome

Budesonide-formoterol taken as needed is an emerging treatment for mild asthma.. We used data from the SYGMA studies to assess the safety of As-needed budesonide-formoterol compared with As-needed terbutaline and compared with maintenance budesonide.. SYGMA 1 and 2 were 52-week, double-blind, parallel-group studies in patients aged ≥ 12 years with physician-assessed mild asthma. Patients were randomized to As-needed budesonide-formoterol 200/6 μg, twice-daily budesonide 200 μg as maintenance plus As-needed terbutaline 0.5 mg, and As-needed terbutaline 0.5 mg (SYGMA 1 only). Adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs (DAEs), and study-defined asthma-related discontinuations from corresponding treatment groups in both studies were pooled. SYGMA 1 data were used for comparisons with As-needed terbutaline alone.. The pooled analysis included 3366 patients in the As-needed budesonide-formoterol group and 3369 in the budesonide maintenance group, with AEs in 40.8% and 42.5% of patients, respectively. Common AEs included viral upper respiratory tract infection (viral URTI) and URTI. SAE, DAE, and asthma-related discontinuation rates were similar with As-needed budesonide-formoterol and maintenance budesonide. Potential local and systemic corticosteroid class effects were reported in ≤ 1% of patients for each budesonide-containing regimen. In SYGMA 1, AEs were more common in the As-needed terbutaline (n = 1277) than As-needed budesonide-formoterol (n = 1277) groups (42.7 vs. 38.0%), as were DAEs (2.9 vs. 0.8%) and asthma-related discontinuations (1.6 vs. 0.3%).. Budesonide-formoterol anti-inflammatory reliever therapy is generally well-tolerated in patients with mild asthma and has a safety profile similar to that of daily budesonide. No new safety signals were identified. CLINICALTRIAL.. NCT02149199 (SYGMA 1) and NCT02224157 (SYGMA 2).

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Terbutaline

Medication adherence is challenging for adolescents. In mild asthma, as-needed budesonide-formoterol (BUD-FORM) reduces severe exacerbations compared with as-needed short-acting beta. This post hoc pooled analysis of Symbicort Given as-needed in Mild Asthma (SYGMA) 1 and 2 assessed the efficacy and safety of as-needed BUD-FORM in adolescents.. SYGMA 1 and 2 were 52-week, double-blind studies (NCT022149199; NCT02224157) in patients 12 years or older with mild asthma. Patients were randomized to twice-daily placebo + as-needed BUD-FORM 200/6 μg, twice-daily BUD 200 μg + as-needed terbutaline (BUD maintenance), or twice-daily placebo + as-needed terbutaline 0.5 mg (SYGMA 1 only). Annualized severe exacerbation rates, maintenance treatment adherence, and safety (including change in height) were compared between treatment groups in adolescents (aged ≥12 to <18 years).. Severe exacerbation rate was similar with as-needed BUD-FORM and BUD maintenance (pooled analysis: 0.08 vs 0.07/y; P = .634), and was significantly lower with as-needed BUD-FORM versus as-needed terbutaline (SYGMA 1: 0.04 vs 0.17/y; P = .005). Median adherence was 73% in SYGMA 1 and 51% in SYGMA 2. Change in height from baseline in adolescents aged ≥12 years to <14 years was significantly greater with as-needed BUD-FORM (4.8 cm) versus BUD maintenance (3.9 cm) (pooled: P < .046), and was similar between as-needed BUD-FORM (4.5 cm) and as-needed terbutaline (4.1 cm) (SYGMA 1: P = .500). No new or unexpected safety concerns were identified.. In adolescents with mild asthma, as-needed BUD-FORM was superior to as-needed terbutaline for severe exacerbation reduction, with similar efficacy to BUD maintenance. As-needed BUD-FORM provides an alternative treatment option for adolescents with mild asthma, without needing daily treatment.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Terbutaline; Treatment Outcome

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Formoterol Fumarate; Humans

Symptom-driven low-dose inhaled corticosteroid-formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide-formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2-94.8%) out of 150 who were randomised to as-needed budesonide-formoterol, and by 63 (40%, 95% CI 32.7-48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide-formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide-formoterol 92% (n=138) were confident using it as a reliever at the end of the study.Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide-formoterol as needed, indicating that most patients preferred as-needed corticosteroid-formoterol therapy if they had experienced it.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Patient Preference; Treatment Outcome

In mild asthma, as-needed budesonide-formoterol is superior or noninferior to maintenance budesonide plus as-needed short-acting β. Participants were randomised 1:1 to as-needed budesonide-formoterol (200/6 μg Turbuhaler, one actuation) or maintenance budesonide (200 μg Turbuhaler, one actuation twice a day) with as-needed terbutaline (250 μg, two actuations) for 52 weeks. 110 participants had electronic monitors attached to their study inhalers which captured the time and date of every actuation. Key outcome measures were patterns of ICS and β. Participants randomised to as-needed budesonide-formoterol had more days with no ICS use compared with maintenance budesonide (median total days of no use 156. The timing of ICS dose when self-titrated to β

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans

To study the effect of intermittent versus daily inhalation of budesonide on pulmonary function and fractional exhaled nitric oxide (FeNO) in children with mild persistent asthma.. A total of 120 children, aged 6-14 years, with mild persistent asthma who attended the hospital from January 2016 to January 2018 were enrolled. The children were divided into an intermittent inhalation group with 60 children (inhalation of budesonide 200 μg/day for 6 weeks when symptoms of asthma appeared) and a daily inhalation group with 60 children (continuous inhalation of budesonide 200 μg/day) by stratified randomization. The children were followed up at months 3, 6, 9, and 12 of treatment. The two groups were compared in terms of baseline data, changes in FeNO and pulmonary function parameters, amount of glucocorticoid used, number of asthma attacks, and asthma control.. At the start of treatment, there were no significant differences in baseline data, FeNO, and pulmonary function between the two groups (P>0.05). Over the time of treatment, FeNO gradually decreased and pulmonary function parameters were gradually improved in both groups (P<0.001). Compared with the intermittent inhalation group, the daily inhalation group had a better effect in reducing FeNO and increasing the predicted percentage of forced expiratory volume in 1 second (FEV1%pred) (P<0.001). The inhalation method and treatment time had an interaction effect on FeNO and pulmonary function parameters (P<0.001). In the daily inhalation group, FeNO and lung function parameters were improved rapidly and stabilized after 3 months of treatment, while those in the intermittent inhalation group stabilized after 6 months. After 12 months of treatment, there were no significant differences in the increases in body height and body weight and the degree of disease control between the two groups (P>0.05). Compared with the daily inhalation group, the intermittent inhalation group had a significantly lower amount of budesonide inhaled (P<0.05) and a significantly higher number of asthma attacks (P<0.05).. Intermittent inhalation and daily inhalation of budesonide can achieve the same level of asthma control in children with mild persistent asthma and both have no influence on the increases in body height and body weight. Daily inhalation of budesonide can produce a better efficiency in reduing FeNO and increasing FEV1%pred. Although intermittent inhalation can reduce the amount of glucocorticoid used, it may lead to a higher risk of asthma attacks.

Topics: Administration, Inhalation; Adolescent; Asthma; Budesonide; Child; Forced Expiratory Volume; Humans; Nitric Oxide

In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Māori and Pacific peoples, populations with worse asthma outcomes.. The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable.. Seventy-two participants (8%) identified as Māori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70).. The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Māori and Pacific adults compared with New Zealand European/Other.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Case-Control Studies; Disease Progression; Drug Therapy, Combination; Ethnicity; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; New Zealand; Outcome Assessment, Health Care; Terbutaline; Treatment Outcome

Asthma is a common chronic airway inflammatory disease. Exacerbations of asthma not only accelerate the progression of the disease but also increase the incidence of hospitalization and death. Studies have shown that air pollution is a high-risk factor for asthma exacerbations. However, few treatment strategies have been recommended to reduce the risk of severe air pollution-related asthma exacerbations.. This is a single-centre, prospective, randomized and standard treatment parallel control clinical trial. Seventy-two asthma patients in the nonexacerbation stage according to GINA guidelines 2017 will be recruited and randomized into the rescue intervention strategy (RIS) group and control group. Original treatments for the participants will include no use of inhaled medicine, the use of short-acting β-agonists (SABA) on demand or the use of budesonide/formoterol (160 μg/4.5 μg/dose, 1-2 dose/time, b.i.d.). The rescue intervention strategy for the RIS group will be budesonide/formoterol plus the original treatment until the severe pollution ends (air quality index, AQI < 200). The control group will maintain the original treatment. The follow-up observation period will last 1 year. The primary outcome is the frequency of asthma exacerbations per year. Secondary outcomes include the mean number of unplanned outpatient visits, emergency visits, hospitalizations, medical costs and mortality caused by asthma exacerbations per patient per year.. The results of this trial will provide a novel strategy to guide clinical practice in decreasing the risk of asthma exacerbations under severe air pollution.. ChiCTR ChiCTR1900026757 . Registered on 20 October 2019-retrospectively registered.

Topics: Administration, Inhalation; Air Pollution; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Prospective Studies; Randomized Controlled Trials as Topic

In adults with mild asthma, a combination of an inhaled corticosteroid with a fast-onset long-acting β-agonist (LABA) used as reliever monotherapy reduces severe exacerbations compared with short-acting β-agonist (SABA) reliever therapy. We investigated the efficacy of combination budesonide-formoterol reliever therapy compared with maintenance budesonide plus as-needed terbutaline.. We did a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial at 15 primary care or hospital-based clinical trials units and primary care practices in New Zealand. Participants were adults aged 18-75 years with a self-reported doctor's diagnosis of asthma who were using SABA for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids in the previous 12 weeks. We randomly assigned participants (1:1) to either reliever therapy with budesonide 200 μg-formoterol 6 μg Turbuhaler (one inhalation as needed for relief of symptoms) or maintenance budesonide 200 μg Turbuhaler (one inhalation twice daily) plus terbutaline 250 μg Turbuhaler (two inhalations as needed). Participants and investigators were not masked to group assignment; the statistician was masked for analysis of the primary outcome. Six study visits were scheduled: randomisation, and weeks 4, 16, 28, 40, and 52. The primary outcome was the number of severe exacerbations per patient per year analysed by intention to treat (severe exacerbations defined as use of systemic corticosteroids for at least 3 days because of asthma, or admission to hospital or an emergency department visit because of asthma requiring systemic corticosteroids). Safety analyses included all participants who had received at least one dose of study treatment. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616000377437.. Between May 4, 2016, and Dec 22, 2017, we assigned 890 participants to treatment and included 885 eligible participants in the analysis: 437 assigned to budesonide-formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. Severe exacerbations per patient per year were lower with as-needed budesonide-formoterol than with maintenance budesonide plus terbutaline as needed (absolute rate per patient per year 0·119 vs 0·172; relative rate 0·69, 95% CI 0·48-1·00; p=0·049). Nasopharyngitis was the most common adverse event in both groups, occurring in 154 (35%) of 440 patients receiving as-needed budesonide-formoterol and 144 (32%) of 448 receiving maintenance budesonide plus terbutaline as needed.. In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. The findings support the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid-formoterol reliever therapy is an alternative regimen to daily low-dose inhaled corticosteroid for patients with mild asthma.. Health Research Council of New Zealand.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Administration Schedule; Equivalence Trials as Topic; Female; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Severity of Illness Index; Terbutaline; Treatment Outcome; Young Adult

Genetic variation may differentially modify drug and placebo treatment effects in randomized clinical trials. In asthma, although lung function and asthma control improvements are commonplace with placebo, pharmacogenomics of placebo vs. drug response remains unexamined. In a genomewide association study of subjective and objective outcomes with placebo treatment in Childhood Asthma Management Program of nedocromil/budesonide vs. placebo (N = 604), effect estimates for lead single nucleotide polymorphisms (SNPs) were compared across arms. The coughing/wheezing lead SNP, rs2392165 (β = 0.94; P = 1.10E-07) mapped to BBS9, a gene implicated in lung development that contains a lung function expression quantitative trait locus. The effect was attenuated with budesonide (P

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Cough; Cytoskeletal Proteins; Female; Genome-Wide Association Study; Humans; Male; Microtubule-Associated Proteins; Nedocromil; Patient Reported Outcome Measures; Pharmacogenomic Testing; Placebo Effect; Polymorphism, Single Nucleotide; Respiratory Sounds; Treatment Outcome; Vital Capacity

The aim of this study was to explore the clinical effect of montelukast sodium chewable tablets combined with inhaled budesonide in the treatment of pediatric asthma and its influence on inflammatory factors. One hundred and thirty-five asthmatic children were randomly divided into montelukast sodium group, budesonide group and combined group. Clinical symptoms, lung function, inflammatory factors and immune related indices of patients in each group were observed and recorded. After treatment, the times to disappearance of wheezes, dyspnea, asthma and hospital stay in the combined group were significantly shorter than those in the single-drug group (all p < 0.001). Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF) were significantly higher than those before treatment, and in the combined group value were significantly higher than in the single-drug group in the same period (all p < 0.001). Tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-8 and hypersensitive C-reactive protein (hs-CRP) were significantly lower than before treatment, and the combined group was significantly lower than the single-drug group in the same period (all p < 0.05). The number of CD4

Topics: Acetates; Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cyclopropanes; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Inflammation; Male; Quinolines; Respiratory Function Tests; Sulfides; Tablets; Treatment Outcome

Corticosteroids are the most potent drugs for the control of severe equine asthma, but adverse effects limit their chronic systemic administration. Inhaled medications allow for drug delivery directly into the airways, reducing the harmful effects of these drugs.. To evaluate the efficacy of inhaled budesonide specifically formulated for the equine use and administered by a novel inhalation device in horses with severe asthma.. Experimental studies in horses with naturally occurring asthma with cross-over, randomised, blinded experimental designs.. In Study 1, there was a marked and significant improvement in the lung function of all horses treated with budesonide and dexamethasone. Neutrophil percentages in bronchoalveolar fluid decreased in all horses treated with dexamethasone and in four of six horses treated with budesonide. Serum cortisol and blood ACTH concentrations decreased with both treatments. In Study 2, there was a significant improvement in the lung function with all dosages of budesonide, and the effects of higher dosages were comparable to those of dexamethasone. Dexamethasone and budesonide at the two higher dosages induced a significant decrease of cortisol concentrations.. The Respimat. Administration of budesonide with the Respimat

Topics: Animals; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Horse Diseases; Horses; Random Allocation

In double-blind, placebo-controlled trials, budesonide-formoterol used on an as-needed basis resulted in a lower risk of severe exacerbation of asthma than as-needed use of a short-acting β. We conducted a 52-week, randomized, open-label, parallel-group, controlled trial involving adults with mild asthma. Patients were randomly assigned to one of three treatment groups: albuterol (100 μg, two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms) (albuterol group); budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol (budesonide maintenance group); or budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed) (budesonide-formoterol group). Electronic monitoring of inhalers was used to measure medication use. The primary outcome was the annualized rate of asthma exacerbations.. The analysis included 668 of 675 patients who underwent randomization. The annualized exacerbation rate in the budesonide-formoterol group was lower than that in the albuterol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49; 95% confidence interval [CI], 0.33 to 0.72; P<0.001) and did not differ significantly from the rate in the budesonide maintenance group (absolute rate, 0.195 in the budesonide-formoterol group vs. 0.175 in the budesonide maintenance group; relative rate, 1.12; 95% CI, 0.70 to 1.79; P = 0.65). The number of severe exacerbations was lower in the budesonide-formoterol group than in both the albuterol group (9 vs. 23; relative risk, 0.40; 95% CI, 0.18 to 0.86) and the budesonide maintenance group (9 vs. 21; relative risk, 0.44; 95% CI, 0.20 to 0.96). The mean (±SD) dose of inhaled budesonide was 107±109 μg per day in the budesonide-formoterol group and 222±113 μg per day in the budesonide maintenance group. The incidence and type of adverse events reported were consistent with those in previous trials and with reports in clinical use.. In an open-label trial involving adults with mild asthma, budesonide-formoterol used as needed was superior to albuterol used as needed for the prevention of asthma exacerbations. (Funded by AstraZeneca and the Health Research Council of New Zealand; Novel START Australian New Zealand Clinical Trials Registry number, ACTRN12615000999538.).

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged

Several gene variants are associated with a response to an inhaled corticosteroids (ICSs) treatment in patients with bronchial asthma. A variant of the glucocorticoid-induced transcript 1 (GLCCI1) genes has previously been associated with decreased lung function improvement upon treatment with ICSs in patients with bronchial asthma. Another report has also demonstrated that this genetic biomarker did not influence the change in flow volume in 1 second. However, no studies have considered the treatment content and the GLCCI1 variants. We were able to determine the relationship between the pulmonary function and clinical features and the variant of the GLCCI1 in Japanese asthmatic patients receiving long-term ICS treatment.. In this study, 405 patients with bronchial asthma, who were receiving ICS and living in Japan, were recruited, genotyped and underwent pulmonary function tests. To identify the GLCCI1 protein expression cells, endobronchial biopsy specimens were examined.. We found that the pulmonary function was not significantly different in the homozygotes compared to the wild types. Also, the homozygotes increased the risk of a sustained step-up of the asthma treatment when compared to the wild type and heterozygotes. GLCCI1-positive cells were localized to the bronchial epithelial cells. The amount of GLCCI1 protein that cultured epithelial cells harboring GLCCI1 variants produced was less than the GLCCI1 wild type in the presence of a corticosteroid.. A worsening of pulmonary function caused by GLCCI1 variants could be prevented due to recently used medications based on new action mechanisms.

Topics: Anti-Inflammatory Agents; Asthma; Bronchoscopy; Budesonide; Cells, Cultured; Female; Fluticasone; Gene Expression Regulation; Genetic Variation; Genotype; Glucocorticoids; Humans; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Real-Time Polymerase Chain Reaction; Receptors, Glucocorticoid; Respiratory Function Tests; Respiratory Mucosa; RNA; Treatment Outcome

Variation in response to the most commonly used class of asthma controller medication, inhaled corticosteroids, presents a serious challenge in asthma management, particularly for steroid-resistant patients with little or no response to treatment.. We applied a systems biology approach to primary clinical and genomic data to identify and validate genes that modulate steroid response in asthmatic children.. We selected 104 inhaled corticosteroid-treated asthmatic non-Hispanic white children and determined a steroid responsiveness endophenotype (SRE) using observations of 6 clinical measures over 4 years. We modeled each subject's cellular steroid response using data from a previously published study of immortalized lymphoblastoid cell lines under dexamethasone (DEX) and sham treatment. We integrated SRE with immortalized lymphoblastoid cell line DEX responses and genotypes to build a genome-scale network using the Reverse Engineering, Forward Simulation modeling framework, identifying 7 genes modulating SRE.. Three of these genes were functionally validated by using a stable nuclear factor κ-light-chain-enhancer of activated B cells luciferase reporter in A549 human lung epithelial cells, IL-1β cytokine stimulation, and DEX treatment. By using small interfering RNA transfection, knockdown of family with sequence similarity 129 member A (FAM129A) produced a reduction in steroid treatment response (P < .001).. With this systems-based approach, we have shown that FAM129A is associated with variation in clinical asthma steroid responsiveness and that FAM129A modulates steroid responsiveness in lung epithelial cells.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Biomarkers, Tumor; Budesonide; Cell Line; Child; Child, Preschool; Dexamethasone; Epithelial Cells; Female; Humans; Male; Nedocromil; Neoplasm Proteins; Polymorphism, Single Nucleotide; Systems Biology; Transcriptome

Prescribed inhaled corticosteroid (ICS) doses in asthma have been studied in cross-sectional settings whereas long-term follow-up studies have not been carried out.. To evaluate prescribed medication longitudinally by calculating cumulative ICS doses and dose changes in a cohort of new-onset adult asthma during 12 years and in different groups of asthma control.. A total of 203 patients were followed for 12 years as part of Seinäjoki Adult Asthma Study (SAAS). All asthma-related visits and prescribed medication over the study period were collected from medical records.. Total cumulative ICS dose for the 12-year follow-up period was 3.4g (±SEM 0.1) per patient. Both respiratory specialists and GPs prescribed step-ups and step-downs in ICS treatment and in total 649 dose changes were noted during the follow-up (median 3(1-5) per patient). Patients with uncontrolled asthma received higher ICS doses throughout the follow-up period, and therefore, cumulative 12-year ICS dose (3.8g ± SEM 0.2) in this group was higher than that in those with partially controlled (3.4g ± SEM 0.2) or controlled disease (2.9g ± SEM 0.2) (p = 0.0001). Patients with uncontrolled asthma were also prescribed a higher number of ICS dose changes than patients with controlled disease.. Despite frequent dose changes and high ICS doses during the 12-year follow-up, the level of asthma control remained poor in patients with uncontrolled asthma. This suggests that high ICS doses may not be effective enough for management of disease in patients with uncontrolled adult-onset asthma and novel targeted treatments are required.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Finland; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies

Patients with mild asthma often rely on inhaled short-acting β. We conducted a 52-week, double-blind, multicenter trial involving patients 12 years of age or older who had mild asthma and were eligible for treatment with regular inhaled glucocorticoids. Patients were randomly assigned to receive twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed or budesonide maintenance therapy with twice-daily budesonide (200 μg) plus terbutaline (0.5 mg) used as needed. The primary analysis compared budesonide-formoterol used as needed with budesonide maintenance therapy with regard to the annualized rate of severe exacerbations, with a prespecified noninferiority limit of 1.2. Symptoms were assessed according to scores on the Asthma Control Questionnaire-5 (ACQ-5) on a scale from 0 (no impairment) to 6 (maximum impairment).. A total of 4215 patients underwent randomization, and 4176 (2089 in the budesonide-formoterol group and 2087 in the budesonide maintenance group) were included in the full analysis set. Budesonide-formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval [CI], 0.10 to 0.13) and 0.12 (95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide-formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.. In patients with mild asthma, budesonide-formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide-formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group. (Funded by AstraZeneca; SYGMA 2 ClinicalTrials.gov number, NCT02224157 .).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Maintenance Chemotherapy; Male; Medication Adherence; Middle Aged; Proportional Hazards Models; Severity of Illness Index; Surveys and Questionnaires; Terbutaline; Young Adult

In patients with mild asthma, as-needed use of an inhaled glucocorticoid plus a fast-acting β. We conducted a 52-week, double-blind trial involving patients 12 years of age or older with mild asthma. Patients were randomly assigned to one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed (terbutaline group), twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide-formoterol group), or twice-daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group). The primary objective was to investigate the superiority of as-needed budesonide-formoterol to as-needed terbutaline with regard to electronically recorded weeks with well-controlled asthma.. A total of 3849 patients underwent randomization, and 3836 (1277 in the terbutaline group, 1277 in the budesonide-formoterol group, and 1282 in the budesonide maintenance group) were included in the full analysis and safety data sets. With respect to the mean percentage of weeks with well-controlled asthma per patient, budesonide-formoterol was superior to terbutaline (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval [CI], 1.00 to 1.30; P=0.046) but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73). The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide-formoterol, and 0.09 with budesonide maintenance therapy; the rate ratio was 0.36 (95% CI, 0.27 to 0.49) for budesonide-formoterol versus terbutaline and 0.83 (95% CI, 0.59 to 1.16) for budesonide-formoterol versus budesonide maintenance therapy. The rate of adherence in the budesonide maintenance group was 78.9%. The median metered daily dose of inhaled glucocorticoid in the budesonide-formoterol group (57 μg) was 17% of the dose in the budesonide maintenance group (340 μg).. In patients with mild asthma, as-needed budesonide-formoterol provided superior asthma-symptom control to as-needed terbutaline, assessed according to electronically recorded weeks with well-controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide-containing regimens were similar and were lower than the rate with terbutaline. Budesonide-formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy. (Funded by AstraZeneca; SYGMA 1 ClinicalTrials.gov number, NCT02149199 .).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Maintenance Chemotherapy; Male; Medication Adherence; Middle Aged; Surveys and Questionnaires; Terbutaline; Young Adult

Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists.. In the initial cross-sectional phase, patients were randomized to a 6-step training protocol with empty Spiromax and Turbuhaler devices. Patients initially demonstrating ≥1 error with their current device, and then achieving mastery with both Spiromax and Turbuhaler (absence of healthcare professional [HCP]-observed errors), were eligible for the longitudinal phase. In the longitudinal phase, patients were randomized to BF Spiromax or BF Turbuhaler. Co-primary endpoints were the proportions of patients achieving device mastery after three training steps and maintaining device mastery (defined as the absence of HCP-observed errors after 12 weeks of use). Secondary endpoints included device preference, handling error frequency, asthma control, and safety. Exploratory endpoints included assessment of device mastery by an independent external expert reviewing video recordings of a subset of patients.. Four hundred ninety-three patients participated in the cross-sectional phase, and 395 patients in the longitudinal phase. In the cross-sectional phase, more patients achieved device mastery after three training steps with Spiromax (94%) versus Turbuhaler (87%) (odds ratio [OR] 3.77 [95% confidence interval (CI) 2.05-6.95], p < 0.001). Longitudinal phase data indicated that the odds of maintaining inhaler mastery at 12 weeks were not statistically significantly different (OR 1.26 [95% CI 0.80-1.98], p = 0.316). Asthma control improved in both groups with no significant difference between groups (OR 0.11 [95% CI -0.09-0.30]). An exploratory analysis indicated that the odds of maintaining independent expert-verified device mastery were significantly higher for patients using Spiromax versus Turbuhaler (OR 2.11 [95% CI 1.25-3.54]).. In the cross-sectional phase, a significantly greater proportion of patients using Spiromax versus Turbuhaler achieved device mastery; in the longitudinal phase, the proportion of patients maintaining device mastery with Spiromax versus Turbuhaler was similar. An exploratory independent expert-verified analysis found Spiromax was associated with higher levels of device mastery after 12 weeks. Asthma control was improved by treatment with both BF Spiromax and BF Turbuhaler.. EudraCT 2013-004630-14 (registration date 23 January 2014); NCT02570425 .

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Sectional Studies; Dry Powder Inhalers; Female; Formoterol Fumarate; Humans; Logistic Models; Male; Middle Aged; Treatment Outcome; United Kingdom

This is the first study of the inhaled corticosteroid, budesonide, delivered by metered-dose inhaler (BD MDI) using innovative co-suspension delivery technology in adults with asthma.. To characterize the effects of BD delivered by MDI on lung function and safety.. Randomized, double-blind, 4-week cross-over, placebo-controlled, phase IIb study of adults (18-65 years of age) with mild-to-moderate persistent asthma. The subjects received twice-daily BD MDI 320 μg, 160 μg, and placebo MDI, and either BD MDI 80 μg or 40 μg. The primary endpoint was change from baseline in morning trough forced expiratory volume in 1 second (FEV1) at the end of the treatment period (EOT). Secondary endpoints included change from baseline in morning and evening predose peak expiratory flow rate (PEFR), rescue medication use, and Asthma Control Questionnaire 5-question version (ACQ-5) score. Safety was also assessed.. A total of 147 subjects were randomized. All doses of BD MDI improved morning trough FEV1 at EOT, and morning and evening predose PEFR in the last treatment week versus placebo (all p < 0.01), with improvements in trough FEV1 exceeding 100 mL for BD MDI 320 μg, and 160 μg only. Compared with placebo, all BD MDI doses reduced rescue medication use in the last week of treatment (p < 0.01) and improved ACQ-5 scores at EOT (all p < 0.01). All treatments were well tolerated.. Analysis of the data demonstrated greater efficacy improvements for the higher doses of BD MDI (320 μg and 160 μg), with similar adverse event profiles compared with the lower doses. Hence, BD MDI 320 μg and 160 μg warrant further evaluation in subjects with persistent asthma.Clinical trial NCT02105012, www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Female; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome; Young Adult

Topics: Administration, Inhalation; Adult; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Disease Progression; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Terbutaline

Topics: Adolescent; Adult; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Formoterol Fumarate; Humans; Male; Terbutaline; Young Adult

Present study is done to analyze the advantages and disadvantages in application of oxygen-driven aerosol and aerosol inhalation by air compressor for the pediatric asthma. A total of 180 patients with pediatric bronchial asthma were randomized into the oxygen-driven aerosol group (Group A, n=90) and the air compressor-driven aerosol group (Group B, n=90). Patients in both groups received 0.5 mg budesonide suspension, 0.2 mg salbutamol and 4 mL normal saline, and following the treatment, we recorded the excellence rate, improvement rate, total effectiveness rate, and the changes in oxyhemoglobin saturation (SaO2) before and after treatment, and the remission time in two groups. In Group A, patients had a higher total effectiveness rate (95.79% vs. 75.79%) but a lower failure rate (4.21% vs. 24.21%) than those in the Group B, with statistically significant differences (p>0.05). Following the aerosol inhalation, SaO2 levels in two groups were ameliorated in comparison with the levels before treatment [Group A: (95.4±0.4) % vs. (80.6±0.8%, Group B: (92.1±1.1)% vs. (79.3±0.7)%] (p<0.05), and the level in Group A following the treatment was higher than that in Group B [(95.4±0.4) % vs. (92.1±1.1)%] (p<0.05). Furthermore, patients in Group A had a longer effective remission time and total remission time than those in Group B, but the differences had no statistical significance (p>0.05). Both of the oxygen-driven aerosol inhalation and aerosol inhalation by air compressor can improve the clinical symptoms of pediatric asthma effectively, but oxygen-driven aerosol inhalation works more efficiently, with an elevated SaO2. Thus, oxygen-driven aerosol inhalation is preferred in clinical practice.

Topics: Administration, Inhalation; Aerosols; Albuterol; Asthma; Budesonide; Child; Compressed Air; Female; Humans; Male; Oxygen; Oxyhemoglobins; Remission Induction; Treatment Outcome

Asthma management may involve a step up in treatment when symptoms are not well controlled. We examined whether budesonide/formoterol maintenance and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus as-needed terbutaline in patients requiring step-up from Step 2 treatment (low-dose inhaled corticosteroids), stratified by baseline reliever use.. A post-hoc analysis utilized data from three clinical trials of 6-12 months' duration. Patients aged ≥12 years with symptomatic asthma uncontrolled despite Step 2 treatment were included. Severe exacerbation rate, lung function and reliever use were analysed, stratified by baseline reliever use (<1, 1-2 and >2 occasions/day).

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Australia; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Formoterol Fumarate; Humans; Lung; Male; Middle Aged; Regression Analysis; Respiratory Therapy; Retrospective Studies; Terbutaline; Treatment Outcome; Young Adult

Topics: Acetates; Adult; Airway Management; Anti-Asthmatic Agents; Asthma; Budesonide; Cyclopropanes; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Monitoring; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Indoleacetic Acids; Male; Middle Aged; Pyridines; Quinolines; Receptors, Immunologic; Receptors, Prostaglandin; Severity of Illness Index; Sulfides; Treatment Outcome

Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the previous symptom-based cutoff for starting ICS by establishing whether there was a differential response to budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control across subgroups identified by baseline asthma symptom frequency.. We did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study, done in 32 countries, with clinic visits every 3 months. Patients (aged 4-66 years) with mild asthma diagnosed within the previous 2 years and no previous regular corticosteroids were randomised to receive once daily, inhaled budesonide 400 μg (those aged <11 years 200 μg) or placebo. Coprimary outcomes for this analysis were time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator. Interaction with baseline symptom frequency was investigated, with patients grouped by more than two symptom days per week and two or fewer symptom days per week (divided into no days to 1 day, and more than 1 day to 2 days). Analysis was done by intention to treat.. Of 7138 patients (n=3577 budesonide; n=3561 placebo), baseline symptom frequency was 0-1 days per week for 2184 (31%) participants, more than 1 and less than or equal to 2 symptom days per week for 1914 (27%) participants, and more than 2 symptom days per week for 3040 (43%) participants. For budesonide versus placebo, time to first SARE was longer across symptom frequency subgroups (hazard ratios 0·54 [95% CI 0·34-0·86] for 0-1 symptom days per week, 0·60 [0·39-0·93] for >1 to ≤2 symptom days per week, 0·57 [0·41-0·79] >2 symptom days per week, p. In mild recent-onset asthma, once daily, low-dose budesonide decreases SARE risk, reduces lung function decline, and improves symptom control similarly across all symptom subgroups. The results do not support restriction of inhaled corticosteroids to patients with symptoms on more than 2 days per week and suggest that treatment recommendations for mild asthma should consider both risk reduction and symptoms.. AstraZeneca.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Middle Aged; Practice Guidelines as Topic

The efficacy and safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI) have been demonstrated in patients with asthma at least 12 years old.. To evaluate the efficacy of 2 formoterol doses added to budesonide as fixed combinations vs budesonide alone in children 6 to younger than 12 years with asthma.. Change in forced expiratory volume in 1 second from baseline to 1 hour after dosing (primary end point), change in forced expiratory volume in 1 second 15 minutes after dosing, and peak expiratory flow 1 hour after dosing at week 12 were statistically significantly greater for budesonide/formoterol 160/9 μg vs budesonide (P ≤ .015 for all comparisons), but not for budesonide/formoterol 160/4.5 μg vs budesonide. Bronchodilator effects, evident 15 minutes after the dose on day 1, were maintained at week 12. Incidence of protocol-defined asthma exacerbations and improvements in asthma symptom-related and quality-of-life outcomes were similar across treatments. There were no notable safety differences among treatments.. Budesonide/formoterol pMDI 160/9 μg showed statistically significant and clinically meaningful lung function improvements vs budesonide pMDI 160 μg, demonstrating appropriateness as a therapeutic option for children 6 to younger than 12 years with asthma symptomatic on ICS alone.. ClinicalTrials.gov Identifier: NCT02091986.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Quality of Life; Treatment Outcome

The optimal management of people with asthma with a significant smoking history is uncertain. The aim of this study was to determine whether the efficacy/safety profile of single combination inhaled corticosteroid (ICS)/long acting beta-agonist (LABA) inhaler maintenance and reliever therapy is influenced by smoking status.. We undertook secondary analyses from an open-label 24-week randomized study of 303 high risk adult asthma patients randomized to budesonide/formoterol 200/6-µg-metred dose inhaler for maintenance (two actuations twice daily) and either budesonide/formoterol 200/6-µg-metred dose inhaler one actuation ('single ICS/LABA maintenance and reliever therapy (SMART)' regimen) or salbutamol 100 µg 1-2 actuations for symptom relief ('Standard' regimen). Smoking status was classified in to three groups, as 'current', 'ex' or 'never', and a smoking/treatment interaction term tested for each outcome variable. The primary outcome variable was number of participants with at least one severe exacerbation.. There were 59 current, 97 ex and 147 never smokers included in the analyses. The smoking status/treatment interaction term was not statistically significant for any of the outcome measures. With adjustment for smoking status, the number of participants with severe exacerbations was lower with the SMART regimen (OR 0.45, 95% CI: 0.26-0.77, P = 0.004; P value for interaction between smoking status and treatment 0.29).. We conclude that the favourable safety/efficacy profile of the SMART regimen applies to patients with high risk asthma, irrespective of smoking status.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Risk; Smoking; Treatment Outcome; Young Adult

Budesonide and formoterol (BF) Spiromax® is a dry powder inhaler designed to deliver BF with maximum ease of use for patients with asthma or chronic obstructive pulmonary disease.. A phase 3b, 12-week, multicenter, double-blind, double-dummy, randomized, controlled trial in patients (≥12 years) with persistent asthma.. to demonstrate non-inferiority of twice-daily BF Spiromax 160/4.5 mcg to BF Turbuhaler® 200/6 mcg in change from baseline in weekly average of daily trough morning peak expiratory flow (PEF). Secondary endpoints included: Patient Satisfaction and Preference Questionnaire scores, change from baseline in evening PEF, trough forced expiratory volume in one second, percentage of symptom-free and rescue-free 24-hour periods, and safety.. The analysis was based on the per-protocol population (BF Spiromax, n = 290; BF Turbuhaler, n = 284). The least squares mean change from baseline to week 12 in morning PEF was: BF Spiromax, 18.8 L/min and BF Turbuhaler, 21.8 L/min. Non-inferiority of BF Spiromax vs BF Turbuhaler was demonstrated (the lower limit of the 95% two-sided confidence interval was -9.02 L/min, which is greater than -15 L/min [the criteria specified for non-inferiority]). The mean difference in the total performance domains scores for BF Spiromax vs BF Turbuhaler were 0.248 at baseline and 0.353 at week 12 (both, p <0.001), indicating statistical superiority for BF Spiromax. No statistical or numerical differences were recorded in the total convenience domain score between the two devices. Scores for 'device preference' and 'willingness to continue' supported BF Spiromax at baseline and at week 12 (p = 0.0005 vs BF Turbuhaler). No significant between-group differences were observed in the other secondary efficacy endpoints. Both treatments were well tolerated, with no significant differences in adverse events or asthma exacerbations.. This study demonstrates the non-inferiority of BF Spiromax vs BF Turbuhaler in patients (≥12 years) with asthma. More patients preferred the Spiromax device over Turbuhaler for its performance, and were willing to continue therapy with BF Spiromax beyond the 12-week study period.. NCT01803555; February 28, 2013.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Dry Powder Inhalers; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Patient Preference; Patient Satisfaction; Peak Expiratory Flow Rate; Treatment Outcome; Young Adult

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction.. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma.. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001).. Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Forced Expiratory Volume; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Lung; Male; Nedocromil; Risk Factors; Sex Factors; Spirometry; Young Adult

Concerns remain about the safety of adding long-acting β2-agonists to inhaled glucocorticoids for the treatment of asthma. In a postmarketing safety study mandated by the Food and Drug Administration, we evaluated whether the addition of formoterol to budesonide maintenance therapy increased the risk of serious asthma-related events in patients with asthma.. In this multicenter, double-blind, 26-week study, we randomly assigned patients, 12 years of age or older, who had persistent asthma, were receiving daily asthma medication, and had had one to four asthma exacerbations in the previous year to receive budesonide-formoterol or budesonide alone. Patients with a history of life-threatening asthma were excluded. The primary end point was the first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization), as assessed in a time-to-event analysis. The noninferiority of budesonide-formoterol to budesonide was defined as an upper limit of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The primary efficacy end point was the first asthma exacerbation, as assessed in a time-to-event analysis.. A total of 11,693 patients underwent randomization, of whom 5846 were assigned to receive budesonide-formoterol and 5847 to receive budesonide. A serious asthma-related event occurred in 43 patients who were receiving budesonide-formoterol and in 40 patients who were receiving budesonide (hazard ratio, 1.07; 95% confidence interval [CI], 0.70 to 1.65]); budesonide-formoterol was shown to be noninferior to budesonide alone. There were two asthma-related deaths, both in the budesonide-formoterol group; one of these patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P=0.002).. Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies; Young Adult

Topics: Administration, Inhalation; Asthma; Budesonide; Delayed-Action Preparations; Disease Progression; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Formoterol Fumarate; Humans; Male; Patient Safety; Risk Assessment; Survival Rate; United States; United States Food and Drug Administration

The stepping down of asthma treatment can be considered when asthma symptoms have been well controlled with inhaled corticosteroids (ICSs)/long-acting β2 adrenergic agonists (LABAs). However, few data are available comparing the efficacy between two step-down strategies, to reduce ICS/LABA dose or to withdraw LABA continuing ICS, in well-controlled asthmatics.. This was a prospective multicentre randomized, two-arm, controlled study. Ninety-one asthmatic patients controlled by budesonide/formoterol combination (BFC) 320/9 μg twice daily were assigned to 2 stepping-down treatments as follows: the BFC group; BUD/FM 160/4.5 μg twice daily, and the ICS group; ICS (budesonide 400 μg twice daily or equivalent dose of ICS) without LABA, and followed for 12 weeks. The primary outcome was the incidence of asthma exacerbations. Asthma control, pulmonary function tests, and fraction of exhaled nitric oxide (FeNO) were evaluated at the beginning and end of the period.. The incidence of exacerbations was 16.3% in the BFC groups and 12.5% in the ICS group, which were not different between the groups (p = 0.766). No significant differences were found in QOL score and FeNO between 0 week and 12 week in the both group. FEV1 and FEV1 percentage of the predicted value were lower at week 12 than at week 0 in the ICS group, but not in the BFC group.. The two step-down strategies for 12 weeks have equal acceptability in well-controlled asthmatics treated with medium-dose of BFC, however, withdrawal of LABA may have potential risk to deteriorate FEV1.. This study was registered to UMIN-CTR (http://www.umin.ac.jp/ctr/), UMIN000010333.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Disease Progression; Drug Therapy, Combination; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Incidence; Male; Middle Aged; Nitric Oxide; Outcome Assessment, Health Care; Prospective Studies; Respiratory Function Tests

Despite advances in asthma treatment, severe asthma (SA) still results in high morbidity and use of health resources. Our hypothesis was that SA patients would achieve adequate control with a systematic protocol, including oral corticosteroids, budesonide/formoterol maintenance and reliever therapy and a multidisciplinary approach to improve adherence.. Non-controlled (NC) SA patients were enrolled to receive 2 weeks of oral corticosteroids and 12 weeks of formoterol + budesonide. Assessments included asthma control questionnaire (ACQ), asthma control test (ACT), daily symptom diary, lung function and health-related quality of life (HRQoL) questionnaires.. Of 51 patients, 13 (25.5%) achieved control. NC patients had higher utilization of health resources and higher exacerbation rates. Both controlled (C) and NC patients had significantly reduced ACQ scores after oral corticosteroid treatment. After 12 weeks, C patients continued improving. NC patients did not have significant changes. A similar pattern was found regarding lung function, use of rescue medication, and days free of symptoms. After 2 weeks of oral corticosteroids, an increase occurred in those who achieved the ACQ cut off; however, 53.8% of C patients had an ACQ < 1.57 versus 21.1% of NC patients (p = 0.03). Both groups had low HRQoL at baseline with improvement after intervention.. Despite rigorous, optimized follow-up treatment, 75% of SA patients did not achieve adequate symptom control and presented with impaired quality of life. Conversely, application of a low-cost, easy to implement systematic protocol can prevent up to 25% of SA patients from up-titrating to new and complex therapies, thus reducing costs and morbidity.. Retrospectively registered at ClinicalTrial.gov on 22 February 2010 ( NCT01089322 ).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Brazil; Bronchodilator Agents; Budesonide; Female; Formoterol Fumarate; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Quality of Life; Respiratory Function Tests; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Various inhaled corticosteroids (ICSs) are available to control the symptoms of asthma. Although beclomethasone dipropionate (BDP) and budesonide (BUD) are one of the oldest ICSs, their wide availability and low cost make them attractive options in developing countries. Due to lack of consensus on which of the two drugs is better for controlling mild persistent asthma, we undertook this study to compare the efficacy of these two drugs by measuring the change in percentage predicted forced expiratory volume in one second (FEV 1 ) from baseline in children with mild persistent asthma.. A double-blind, randomized, parallel group study was conducted in children 7-15 yr of age with newly diagnosed asthma. Of the 85 cases of mild persistent asthma, 42 received BUD while 43 received BDP at a dose of 400 µg/day using pressurized metered-dose inhaler with valved spacer for two months. The outcomes measured were change in FEV 1 , symptom scores and side effects.. There was a significant (P < 0.05) improvement in FEV 1 in BUD group (98.43 ± 4.63%) than in BDP group (95.65 ± 5.66%) at the end of two months of treatment. The mean symptom scores in BUD group (0.28 ± 1.22) and BDP group (0.43 ± 1.52) were comparable after two months. No side effects were seen in either group.. FEV 1 was significantly greater in BUD group than BDP group. Improvement in symptoms and incidence of side effects were similar. Our findings indicate that both BDP and BUD can be used effectively in the management of children with mild persistent asthma. [CTRI No: CTRI/2013/03/003495].

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male

While several randomized control trials (RCTs) have evaluated the use of fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual center RCT, we assessed whether a treatment strategy based on FeNO levels, adjusted for atopy, reduces asthma exacerbations compared with the symptoms-based management (controls). Children with asthma from hospital clinics of two hospitals were randomly allocated to receive an a-priori determined treatment hierarchy based on symptoms or FeNO levels. There was a 2-week run-in period and they were then reviewed 10 times over 12-months. The primary outcome was the number of children with exacerbations over 12-months. Sixty-three children were randomized (FeNO = 31, controls = 32); 55 (86%) completed the study. Although we did achieve our planned sample size, significantly fewer children in the FeNO group (6 of 27) had an asthma exacerbation compared to controls (15 of 28), P = 0.021; number to treat for benefit = 4 (95% CI 3-24). There was no difference between groups for any secondary outcomes (quality of life, symptoms, FEV1 ). The final daily inhaled corticosteroids (ICS) dose was significantly (P = 0.037) higher in the FeNO group (median 400 µg, IQR 250-600) compared to the controls (200, IQR100-400). Taking atopy into account when using FeNO to tailor asthma medications is likely beneficial in reducing the number of children with severe exacerbations at the expense of increased ICS use. However, the strategy is unlikely beneficial for improving asthma control. A larger study is required to confirm or refute our findings.

Topics: Adolescent; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Exhalation; Female; Fluticasone; Humans; Male; Nitric Oxide; Quality of Life; Treatment Outcome

Topics: Asthma; Biomarkers; Bronchodilator Agents; Budesonide; Child, Preschool; Dermatitis, Atopic; Dipeptidyl Peptidase 4; Eczema; Humans; Infant; Ki-1 Antigen; Lung; Respiratory Function Tests; Th1 Cells; Th1-Th2 Balance; Th2 Cells

This phase 2/3 randomised, parallel-group, placebo-controlled trial investigated oral corticosteroid (OCS)-sparing efficacy, safety and tolerability of nebulised budesonide (Bud) administered with a novel computer-controlled, compressor-driven inhalation system (AKITA) as add-on therapy to Global Initiative for Asthma step 5. Patients (18-65 years) with OCS-dependent asthma were randomised (2:1:1:1) to receive 18-week, twice-daily, double-blind treatment with AKITA inhaled corticosteroid (AICS)-Bud 1 mg, AICS-Bud 0.5 mg, AICS-placebo or open-label Bud 1 mg administered by conventional nebuliser (CN-Bud). OCS doses were tapered until week 14. 199 patients started treatment. More AICS-Bud 1 mg (80.0%) than placebo-treated (62.5%) patients had daily OCS doses reduced ≥50%, with clinical stability to week 18 (one-sided p=0.02; treatment difference: 17.5% (95% CI 0.1-34.9%), two-sided p=0.04). Mean±sd forced expiratory volume in 1 s improved (from baseline to week 18) for AICS-Bud 1 mg (239±460 mL, p<0.001) and AICS-Bud 0.5 mg (126±345 mL, p=0.01) but not placebo (93±419 mL, p=0.36) or CN-Bud (137±459 mL, p=0.18). Fewer AICS-Bud 1 mg-treated patients experienced asthma exacerbations (7.5%) compared with placebo (17.5%) or CN-Bud (22.5%). All treatments were well tolerated. Budesonide applied with AKITA allowed significant meaningful OCS reduction in OCS-dependent asthma patients while improving pulmonary function and maintaining exacerbation control.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Safety; Prednisone; Steroids; Treatment Outcome; Young Adult

Patterns of inhaled β2-agonist therapy use during severe asthma exacerbations before hospital attendance are poorly understood.. To assess β2-agonist use prior to hospital attendance.. We undertook an exploratory post hoc analysis of data from a 6-month clinical trial of 303 patients randomised to combination budesonide/formoterol inhaler according to a Single combination inhaler as Maintenance And Reliever Therapy regimen ('SMART') or fixed-dose budesonide/formoterol with salbutamol as reliever ('Standard'). Patterns of β2-agonist use for 14 days before hospital attendance with a severe asthma exacerbation were determined by electronic monitoring of inhaler use.. There were 22 hospital attendances in 16 patients during the study. Seven and nine hospital attendances were eligible for analysis in the SMART and Standard groups, respectively. In both regimens, β2-agonist use increased before hospital attendance, with a median (range) maximum daily number of actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95) salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the day of maximal salbutamol use. There was delay in obtaining medical review despite high β2-agonist use, in 9/16 patients. Different patterns of use were observed, including repeated days of no inhaled corticosteroid despite marked salbutamol use, which occurred in 3/9 patients in the Standard group.. Delay in obtaining medical review in association with high β2-agonist use is common in patients before hospital presentation with severe exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled corticosteroid therapy during severe exacerbations.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Budesonide; Disease Progression; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Hospitalization; Humans; Male; Middle Aged

Data comparing various second-line treatments for asthma with subjective and objective assessment are lacking. This study aimed to compare the efficacy and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide in patients with mild to moderate persistent asthma.. Patients, all of whom were concurrently using inhaled budesonide (400 µg), were treated for 6 months with formoterol (12 µg), montelukast (10 mg), doxofylline (400 mg), or tiotropium (18 µg). Outcomes included forced expiratory volume in 1 second (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom scores (daytime and nighttime), and assessment of tolerability and rescue medication use.. A total of 297 patients completed the study. In all 4 groups, significant improvements were observed in all the outcome measures, with formoterol treatment having greater and earlier improvements than the other 3 second-line controller medications with budesonide. Among the second-line treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a faster rate than doxofylline or tiotropium with budesonide. No patients discontinued the treatment because of adverse reactions.. Among the tested second-line treatment regimens, the budesonide/montelukast combination was found to be superior to either the budesonide/doxofylline or budesonide/tiotropium combination in all the outcome measures without adversely affecting the tolerability of the patients. Further clinical studies with blinding techniques are likely to be useful.

Topics: Acetates; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Respiratory Function Tests; Sulfides; Theophylline; Tiotropium Bromide

To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 μg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI).. This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 μg bid, BUD/FM pMDI 2 × 160/4.5 μg bid, or BUD pMDI 2 × 160 μg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV1 (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1 within confidence intervals (CIs) of 80-125%.. Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI, 0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar.. BUD/FM 2 × 160/4.5 μg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting β2-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Bulgaria; Child; Double-Blind Method; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Hungary; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome; United States; Young Adult

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous disorders encompassing different phenotypes of airflow obstruction, which might differ in their response to treatment.. The aim of this study was to determine distinct phenotypes comprising the syndromes of asthma and COPD and the treatment responsiveness of these phenotypes to inhaled β-agonist, antimuscarinic, and corticosteroid therapy.. We undertook a cross-sectional study with 3 phases. In phase 1, 1,264 participants aged 18 to 75 years with self-reported current wheeze and breathlessness were identified from a random population sample of 16,459. In phase 2, 451 participants attended for detailed assessment, including responsiveness to inhaled salbutamol and ipratropium bromide. In phase 3, 168 steroid-naive participants were enrolled in a 12-week trial of inhaled budesonide. Cluster analysis was performed in 389 participants who completed phase 2 with full data. Treatment responsiveness was compared between phenotypes.. Cluster analysis identified 5 phenotypes: moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, obese-comorbid, mild childhood-onset atopic asthma, and mild intermittent. Bronchodilation after salbutamol was equal to or greater than that after ipratropium for all phenotypes. The moderate-to-severe childhood-onset atopic asthma, asthma-COPD overlap, and obese-comorbid phenotypes had greater efficacy with inhaled corticosteroid treatment than the mild intermittent group.. Cluster analysis of adults with symptomatic airflow obstruction identifies 5 disease phenotypes, including asthma-COPD overlap and obese-comorbid phenotypes, and provides evidence that patients with the asthma-COPD overlap syndrome might benefit from inhaled corticosteroid therapy.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide; Cluster Analysis; Female; Glucocorticoids; Humans; Ipratropium; Male; Middle Aged; Muscarinic Antagonists; Obesity; Phenotype; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.. We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.. Eighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model.. Children with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13(+) innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13(+) ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2(-/-) mice lacking a functional receptor for IL-33.. Pediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.

Topics: Adolescent; Alternaria; Animals; Animals, Newborn; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Aspergillus fumigatus; Asthma; Budesonide; Child; Cladosporium; Disease Models, Animal; Female; Humans; Immunoglobulin E; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13; Interleukin-33; Interleukins; Male; Mice; Mycoses; Omalizumab; Pyroglyphidae; Receptors, Interleukin; Severity of Illness Index; Skin Tests; Th2 Cells

Asthma guidelines recommend monitoring of asthma control. However, in a substantial proportion of children, asthma is poorly controlled and the best monitoring strategy is not known.. We studied two monitoring strategies for their ability to improve asthma outcomes in comparison with standard care (SC): web-based monthly monitoring with the (Childhood) Asthma Control Test (ACT or C-ACT) and 4-monthly monitoring of FENO.. In this randomised controlled, partly blinded, parallel group multicentre trial with a 1-year follow-up, children aged 4-18 with a doctor's diagnosis of asthma treated in seven hospitals were randomised to one of the three groups. In the web group, treatment was adapted according to ACT obtained via a website at 1-month intervals; in the FENO group according to ACT and FENO, and in the SC group according to the ACT at 4-monthly visits. The primary endpoint was the change from baseline in the proportion of symptom-free days (SFD).. Two-hundred and eighty children (mean age 10.4 years, 66% boys) were included; 268 completed the study. Mean changes from baseline in SFD were similar between the groups: -2.1% (web group, n=90), +8.9% (FENO group, n=91) versus 0.15% (SC, n=87), p=0.15 and p=0.78. Daily dose of inhaled corticosteroids (ICS) decreased more in the web-based group compared with both other groups (-200 μg/day, p<0.01), while ACT and SFD remained similar.. The change from baseline in SFD did not differ between monitoring strategies. With web-based ACT monitoring, ICS could be reduced substantially while control was maintained.. NTR 1995.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Monitoring, Physiologic; Netherlands; Prospective Studies; Quality of Life; Respiratory Function Tests; Single-Blind Method; Surveys and Questionnaires; Treatment Outcome

Asthma exacerbations lead to frequent emergency visits and hospitalizations, and are associated with high morbidity and occasionally mortality. New therapeutic strategies are needed. We sought to investigate whether the addition of high-dose inhaled budesonide to standard therapy would shorten the length of stay (LOS) in hospital of children admitted for asthma exacerbations.. The study was designed as a single-center, double-blind, placebo-controlled and parallel-group trial. Children aged 7-72 months and admitted with an asthma exacerbation clinical asthma score (CAS) of between 3 and 9 were allocated to either the budesonide (n = 50) or the placebo (n = 50) group. Hospital LOS was compared between children who received 2 mg/day of budesonide versus placebo in addition to standard management of asthma exacerbation involving oxygen inhalation and β2-agonist, anticholinergic and oral corticosteroid therapy. All patients were assessed every 4 h. Children with a CAS <3, a peripheral oxygen saturation >95% and normal pulmonary function, and those with a symptom-free period of at least 4 h after salbutamol treatment were discharged.. Total hospital LOS was significantly shorter in the budesonide group than in the placebo group (median: 44 vs. 80 h, respectively; p = 0.01). When compared with placebo, the number of inpatients was significantly less in the budesonide group at all the assessed end points (Kaplan-Meier; p = 0.022). Additionally, nebulized budesonide was found to reduce the overall cost of treatment.. We demonstrated that, for children hospitalized for asthma exacerbations, an additional 2 mg/day of nebulized budesonide significantly reduced hospital LOS as well as the overall cost of treatment.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Length of Stay; Male

If asthmatic children cannot obtain sufficient control of their disease, not only do they suffer from asthma symptoms, but the daily life activities of their caregivers are also disrupted. We investigated the effectiveness of an inhaled corticosteroid (ICS) for symptom control in previously ICS-untreated school-aged asthmatic children as well as caregiver treatment satisfaction (CTS).. A multicenter, open-label, single-arm study on 12-week ICS (budesonide Turbuhaler®) monotherapy was undertaken in subjects aged 5-15 years with bronchial asthma not treated with ICS during the previous 3 months. At 0, 4, 8, and 12 weeks after start of ICS administration, Japanese Pediatric Asthma Control Program (JPAC) scores, and CTS scores were summated and lung function measured. At weeks 0 and 12, questionnaires on caregiver anxiety were also assessed.. Seventy-five patients were enrolled, and 69 assessed. Ninety percent of subjects had been treated with asthma controller medication except ICS before study enrollment. JPAC score and CTS score were improved significantly at weeks 4, 8, and 12 (p < 0.001). With regard to CTS, more than half of caregivers showed a perfect score at weeks 8 and 12. There was a significant correlation between JPAC score and CTS score. Lung function and caregiver anxiety were also improved, and good compliance with treatment was observed during the intervention.. If treating ICS-untreated school-aged asthmatic children with uncontrolled symptoms, ICS monotherapy can improve CTS along with improving asthma control.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Caregivers; Child; Female; Humans; Male; Patient Satisfaction; Personal Satisfaction; Risk Factors; Surveys and Questionnaires; Treatment Outcome

Budesonide is approved for delivery using a nebulized solution and dry-powder inhaler, but its use through a pressurized metered-dose inhaler (pMDI) in pediatric patients with asthma has not been determined.. To examine the efficacy and safety of 160 μg twice daily of budesonide through a pMDI vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids.. A 6-week, international, multicenter, double-blinded, parallel-group, phase 2 study randomized 304 pediatric patients (mean age, 9 years; 21.7% <8 years) 1:1 to 160 μg (80 μg × 2 inhalations) twice daily of budesonide through a pMDI or placebo after a 7- to 21-day run-in period. The primary efficacy end point was change from baseline in morning peak expiratory flow (PEF); safety end points included adverse events, vital signs, and discontinuations.. Budesonide treatment significantly improved morning PEF vs placebo; mean treatment effect (budesonide vs placebo) was 13.6 L/min (P < .0001). Budesonide also showed significant improvements vs placebo for forced expiratory volume in 1 second, evening PEF, forced expiratory flow at 25% to 75% of pulmonary volume, reliever medication use, nighttime awakenings, awakenings with reliever use, and percentage of patients with at least 15- and at least 30-L/min increase in morning PEF from baseline. The numbers of patients experiencing adverse events and discontinuations were smaller in the budesonide than in the placebo group. No serious adverse events were reported.. Budesonide at 160 μg twice daily through a pMDI was generally well tolerated and significantly improved lung function, symptoms, rescue medication use, and nighttime awakenings vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Humans; Male; Metered Dose Inhalers; Treatment Outcome

Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management. We previously showed that switching from salmeterol/fluticasone combination (SFC) 50/250 μg bid to a fixed-dose formoterol/budesonide combination (FBC) 9/320 μg bid improved asthma control and pulmonary functions, but not fractional exhaled nitric oxide (FeNO), in patients with asthma not adequately controlled under the former treatment regimen.. To assess whether switching from SFC to FBC improves peripheral airway/alveolar inflammation in asthma (UMIN000009619).. Subjects included 66 patients with mild to moderate asthma receiving SFC 50/250 μg bid for more than 8 weeks. Patients were randomized into FBC 9/320 μg bid or continued the same dose of SFC for 12 weeks. Asthma Control Questionnaire, 5-item version (ACQ5) score, peak expiratory flow, spirometry, FeNO, alveolar NO concentration (CANO), and maximal NO flux in the conductive airways (J'awNO) were measured.. Sixty-one patients completed the study. The proportion of patients with an improvement in ACQ5 was significantly higher in the FBC group than in the SFC group (51.6% vs 16.7%, respectively, p = 0.003). A significant decrease in CANO was observed in the FBC group (from 8.8 ± 9.2 ppb to 4.0 ± 2.6 ppb; p = 0.007) compared to the SFC group (from 7.4 ± 7.8 ppb to 6.4 ± 5.0 ppb; p = 0.266) although there was no significant difference in the changes in pulmonary functions between the 2 groups. Similar significant differences were found in the CANO corrected for the axial back diffusion of NO (FBC, from 6.5 ± 8.2 ppb to 2.3 ± 2.5 ppb; and SFC, from 4.3 ± 5.3 ppb to 3.9 ± 4.3 ppb). There was no difference in the changes in FeNO or J'awNO between the 2 groups.. Switching therapy from SFC to FBC improves asthma control and peripheral airway/alveolar inflammation even though there is no improvement in pulmonary functions, and FeNO in asthmatic patients.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Prospective Studies; Pulmonary Alveoli; Severity of Illness Index; Spirometry; Surveys and Questionnaires; Treatment Outcome

Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses.. A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h.. A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P=.38). However, among cases with high baseline clinical score (≥13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P=.03).. The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma.. ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov

Topics: Acute Disease; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Nebulizers and Vaporizers; Prednisolone

If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, adding a long-acting β2 agonist (LABA) is the preferred treatment. We aimed to compare the effect of two widely available ICS/LABA combinations in these patients in real-life conditions: budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) and a fixed dose of fluticasone propionate/salmeterol (FP/SM).. Inadequately controlled asthma patients treated with a medium dose of ICS alone, with an Asthma Control Questionnaire (ACQ) score >0.75 and using a short-acting β2-agonist (SABA) 2-6 occasions/week, were enrolled. Patients were randomized into two groups and treated with two inhalation twice-daily BUD/FM 160/4.5 μg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation twice-daily FP/SM 250/50 μg plus as-needed procaterol (FP/SM group, n = 15) for 8 weeks.. Both groups showed significant improvement in airway inflammation, pulmonary functions and symptoms from baseline. The SMART group showed significant improvement in the fraction of nitric oxide, ACQ score, rescue medication use and small airway parameter R5-R20 measured by impulse oscillometry compared with the FP/SM group.. For stepping up treatment from ICS alone to an ICS/LABA combination, SMART is preferable for controlling asthma symptoms by suppressing airway inflammation and improving small airway impairment compared with a fixed dose of FP/SM. It may be achieved by the property of BUD/FM itself and as-needed use, but the degree of each contribution must be investigated further.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Treatment Outcome

The role of fixed airflow obstruction (FAO) in asthma is unclear.. To assess the relationship between FAO and clinical features of asthma and the effect of FAO on treatment response.. Post hoc descriptive analysis of data stratified by FAO category (screening post-albuterol FEV1/FVC

Topics: Adolescent; Adult; Airway Obstruction; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Ethanolamines; Formoterol Fumarate; Humans; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Sex Factors; Time Factors; Young Adult

To compare the efficacy of oral Montelukast and inhaled Budesonide as a first line preventive therapy in mild persistent asthma in age group 2-18 y.. This prospective randomized controlled clinical study was conducted for 12 wk. Sixty patients of mild persistent asthma aged 2 to 18 y were randomly allocated to either oral Montelukast (n = 60) or inhaled Budesonide (n = 60) group. Outcomes measured were improvement in peak expiratory flow rate (PEFR), forced expiratory volume 1 s/forced vital capacity (FEV1/FVC), day time and night time symptoms and frequency of exacerbations and need to change medications.. There was significant improvement in PEFR, FEV1/FVC, day time and night time symptoms and frequency of exacerbations in both groups. However, more significant improvement in FEV1/FVC (CI 95 %, p = 0.029) and day time symptoms (CI 95 %, p = 0.002) was seen in Budesonide group compared to Montelukast group.. The present study suggests that oral Montelukast is not inferior to Budesonide in treatment of mild persistent asthma in 2 to 18 y children in terms of control of symptoms and improvement in pulmonary function tests over a 12 wk period. However, there was more significant improvement in day time symptoms, more significant increase in FEV1/FVC ratio and less exacerbation in patients receiving Budesonide compared to those receiving Montelukast. However, side effects due to long term use of steroids such as growth stunting and bone osteopenia should also be considered before recommending. Trial registered at CTRI no. REF/2012/09/004035.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cyclopropanes; Female; Humans; Male; Prospective Studies; Quinolines; Severity of Illness Index; Sulfides

There is no comparative study among asthma patients receiving first-line versus various second-line treatment regimens for mild to moderate persistent asthma.. We assessed the pulmonary function in asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide in a pilot group.. Patients were recruited as per the study criteria and randomly allocated to 4 groups to receive budesonide (400 µg) with formoterol (12 µg), doxofylline (400 mg), montelukast (10 mg), or tiotropium (18 µg) for a period of 3 months. Outcomes included forced expiratory volume in 1 second (FEV1) and rescue medication use.. A total of 167 patients were recruited; among them, 123 patients completed the study. At baseline, no significant difference (P > 0.05) was observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all the groups. At day 90, between-group difference revealed that improvement in FEV1 was significantly (P < 0.05) high for budesonide plus formoterol followed by budesonide plus doxofylline, budesonide plus montelukast, and, lastly, budesonide plus tiotropium. Similarly, within-group comparison revealed a significant (P < 0.05) reduction in rescue medication use in all the groups. The intensity in decrease was more in budesonide plus formoterol group followed by budesonide plus doxofylline, budesonide plus montelukast, and budesonide plus tiotropium groups.. On the basis of our findings, among the second-line treatment regimens, budesonide plus doxofylline and budesonide plus montelukast was found to be better than budesonide plus tiotropium in patients with mild to moderate persistent asthma. Further studies with a larger sample size are likely to be useful.

Topics: Acetates; Adult; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Quinolines; Respiratory Function Tests; Sulfides; Theophylline; Tiotropium Bromide

There are several inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting.. A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 μg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 μg two inhalations bid) and FP/SM (500/50 μg bid) was also switched to BUD/FM (160/4.5 μg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age.. Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved 4 and 8 weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at 8 weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments ([Formula: see text]50 and [Formula: see text]25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old.. These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Longitudinal Studies; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Surveys and Questionnaires

In patients with asthma, single doses of inhaled glucocorticosteroids (ICS) have been reported to have antiinflammatory actions that can be detected several hours after drug administration. However, the onset and duration of the effect have not been investigated. We therefore measured airway blood flow ([Formula: see text]aw) as an index of airway inflammation to determine the time course and dose dependence of the antiinflammatory action of an ICS in 20 patients with moderate asthma receiving regular ICS treatment.. [Formula: see text]aw and spirometry were measured before and serially for 360 minutes after a single inhaled dose of 360 μg, 720 μg, and 1,440 μg budesonide or placebo as well as after four repetitive 720-μg budesonide doses given 30 minutes apart.. Baseline mean [Formula: see text]aw was increased and FEV1 was decreased without significant differences among the 5 treatment days. After budesonide inhalation, there was a transient, dose-dependent decrease in mean [Formula: see text]aw from 12 to 21%, with significant differences from baseline at 60 and 90 minutes for the 720-μg and 1,440-μg doses (P < 0.05). Thirty minutes after four repetitive budesonide administrations, mean [Formula: see text]aw was 28% below baseline (P < 0.05) and remained 11% below baseline after 270 minutes. There was no change in mean FEV1 after any of the treatments.. In subjects with moderate asthma who use ICS regularly, inhaled budesonide caused a transient dose-dependent vasoconstriction in the airway, thereby reversing one manifestation of airway inflammation. These results suggest that a pure controller medication can have immediate beneficial effects not paralleled by changes in airflow. Clinical trial registered with www.clinicaltrials.gov (NCT 01219738).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Spirometry; Treatment Outcome; Young Adult

Many patients with persistent asthma cannot achieve the treatment goal for asthma with a single controller medication. The aim of the present study was to assess lung function and rescue medication use in asthma patients receiving four different categories of drugs in combination with an inhaled corticosteroid. Patients recruited to the study were randomized into four groups to receive budesonide with either formoterol, doxofylline, montelukast or tiotropium for a period of 3 months. Lung function (i.e. forced expiratory volume in 1 s (FEV1 )) and rescue medication use were determined at baseline and on Day 15, 30, 45, 60 and 90 of treatment. A total of 297 patients completed the study. At baseline, no significant differences (P > 0.05) were observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all groups. On Day 90, between-group differences showed that the improvement in FEV1 was significantly (P < 0.05) higher for patients receiving budesonide + formoterol, followed by budesonide + montelukast and budesonide + doxofylline, and least for those receiving budesonide + tiotropium. Similarly, within- and between-group comparisons showed significant (P < 0.05) reductions in rescue medication use in all groups. However, the magnitude of the decrease was greater in the budesonide + formoterol group, followed by the budesonide + montelukast, budesonide + doxofylline and budesonide + tiotropium groups. Based on our findings, among the second-line treatment regimens, budesonide with either montelukast or doxofylline was found to be better than budesonide + tiotropium in patients with mild-to-moderate persistent asthma. Further studies with a longer duration are likely to be useful.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Young Adult

Inhaled corticosteroids (ICSs) are widely used in asthma control. Ciclesonide (CIC) is an ICS with on-site lung activation for potent anti-inflammatory activity.. This study aimed to compare the clinical benefit of CIC with budesonide (BUD) in step-down therapy.. A total of 150 patients with mild-to-moderate asthma well controlled by a combination of ICS and long-acting β2-agonist were randomised to receive either CIC 320 μg (n=75) once daily or 2 inhalations of BUD 200 μg (n=75) twice daily for 12 weeks. The forced expiratory volume in 1s (FEV1), maximum mid-expiratory flow (MMEF) and asthma control test (ACT) scores were measured. Ranked stratification of patients and physicians was assessed.. Drug adherence was significantly higher in the CIC group than in the BUD group (76.0% vs. 58.7%, P=0.03). The FEV1 and MMEF remained stable throughout the 12-week CIC treatment. In the BUD group, FEV1 significantly decreased at weeks 4 and 12. MMEF had a higher value in the CIC group than in the BUD group. Both patients and physicians ranked CIC over BUD.. CIC is more effective and has better drug adherence than BUD as step-down treatment when asthma is well controlled by combination therapy.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Medication Adherence; Middle Aged; Patient Satisfaction; Peak Expiratory Flow Rate; Pregnenediones; Severity of Illness Index; Treatment Outcome; Young Adult

There are significant health disparities between Māori and non-Māori with asthma, a pattern seen between other ethnic populations. This study investigates outcomes for Māori in a randomized controlled trial (RCT) of combination budesonide/formoterol inhaler therapy in asthma.. This 24-week multicentre RCT recruited 303 adult asthma patients, 44 of whom were Māori. Participants were randomized to the single combination budesonide/formoterol inhaler as maintenance and reliever therapy ('SMART') regimen or 'standard' regimen (combination budesonide/formoterol inhaler for maintenance and salbutamol as reliever). Outcomes included patterns of beta-agonist inhaler use including 'high use' of reliever therapy (>8 actuations of budesonide/formoterol in excess of four maintenance doses per day for SMART and >16 actuations per day of salbutamol for standard). Differences in outcomes for Māori versus non-Māori were assessed using an interaction term between ethnicity and treatment.. With adjustment for ethnicity, the SMART group had fewer days of high use (relative rate (RR) 0.57 (95% confidence interval (CI): 0.38-0.85)), days of high use without medical review within 48 h (RR 0.49 (95% CI: 0.32-0.75)) and severe exacerbations (RR 0.54 (95% CI: 0.36-0.81)) compared with standard. The magnitude of the benefit from the SMART regimen was similar in Māori and non-Māori. Regardless of treatment regimen, Māori demonstrated more days of high use, high use without medical review and underuse of maintenance therapy.. The SMART regimen has a favourable risk/benefit profile in Māori. Days of high use, days of high use without medical review and underuse of maintenance treatment were greater in Māori, regardless of treatment regimen.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; New Zealand; Outcome Assessment, Health Care; Prospective Studies; Risk Assessment; Time Factors; Treatment Outcome; Young Adult

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored.. Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma.. We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication.. We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo.. Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cluster Analysis; Female; Follow-Up Studies; Humans; Male; Nedocromil; Phenotype; Prednisolone

Ivy leaves dry extract is registered as an expectorant in patients with respiratory diseases associated with productive cough. Next to its secretolytical properties, bronchospasmolytical effects are described. However only limited data exist about a possible therapeutical effect in asthmatic patients. In this double blind, placebo-controlled, randomized cross-over study, 30 children (median age 9.07 years (min-max: 6-11)) suffering from partial or uncontrolled mild persistent allergic asthma despite long-term treatment with 400 μg budesonide equivalent were investigated. After a four week run-in period, patients either received ivy leaves dry extract for four weeks in addition to their inhaled corticosteroid therapy or placebo, followed by a wash-out phase before switching to the other treatment arm. Lung function, FeNO, exhaled breath condensate pH and life quality was analyzed after each treatment period. There was a significant improvement of MEF(75-25), MEF25 and VC after treatment with ivy leaves dry extract (MEF(75-25) change in the mean 0.115 l/s, p=0.044; MEF25 change in the mean 0.086 l/s, p=0.041; VC change in the mean 0.052 l, p=0.044), but not after treatment with placebo. For the primary outcome parameters (relative change of FEV1 and MEF(75-25) before bronchodilation) no treatment effect could be detected in the cross-over analysis (FEV1 p=0.6763 and MEF(75-25) p=0.6953). This proof-of-concept study indicates that children with mild uncontrolled asthma despite regular inhaled corticosteroid therapy might benefit from an additional therapy with ivy leaves dry extract. However, further studies are needed.

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cough; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Hedera; Humans; Male; Plant Extracts; Plant Leaves

To evaluate Malaysian patients' satisfaction levels and asthma control with Symbicort SMART® in the primary care setting.. This is a cross-sectional, multicentre study involving adult patients with persistent asthma who were prescribed only Symbicort SMART in the preceding one month prior to recruitment. Patients' satisfaction with Symbicort SMART and asthma control were evaluated using the self-administered Satisfaction with Asthma Treatment Questionnaire (SATQ) and the Asthma Control Test (ACT).. Asthma was controlled (ACT score >20) in 189 (83%) of 228 patients. The mean overall SATQ score for patients with controlled asthma was 5.65 indicating a high satisfaction level, which was positively correlated with high ACT scores. There were differences in asthma control based on ethnicity, number of unscheduled visits and treatment compliance.. Symbicort SMART resulted in a high satisfaction level and asthma control among Malaysian patients treated in the primary care setting and it is an effective and appealing treatment for asthmatic patients.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Sectional Studies; Drug Combinations; Ethanolamines; Female; Humans; Malaysia; Male; Middle Aged; Patient Satisfaction; Primary Health Care

Many studies have demonstrated the efficacy of budesonide/formoterol (BUD/FORM) for Maintenance and Reliever Therapy (SMART®) for asthma control. However, there are concerns regarding its over-use and effectiveness.. To examine asthma control and over-use of BUD/FORM in real-life situations.. This study was a hospital-based cross-sectional and multi-center design. Patients were enrolled if they were >12 years old, had persistent asthma, had received BUD/FORM SMART for 3 months or longer, and smoked less than 10 pack-year.. Of the 792 patients who used BUD/FORM for a mean of 28.2 months, all used BUD/FORM as maintenance and only 22.2% of the patients required BUD/FORM to relieve symptoms. The average inhaled corticosteroid dose used was 355.3±154.9μg/day (95% CI: 344.5 to 366.1). In 792 patients, constituting 2,376 person-months of observations, there was only one patient who used more than 12 puffs/ day of BUD/FORM for 3 days, with a rate of 0.015 days per patient per year (95%CI: 0.003 to 0.044), without reporting any adverse events. The percentage of asthma control according to the Asthma Control Test score of 20 or greater was 86.5% (95% CI: 84.1 to 88.9). Overall, the rates per patient per year of emergency room (ER) visits and hospital admissions were 0.18 and 0.21, respectively.. BUD/FORM SMART is effective in real-life clinical practice. On average, patients who received a low dose steroid in the form of BUD/FORM, had a satisfactorily high proportion of asthma control and had a low rate of ER visits and hospitalization. BUD/FORM maintenance and reliever therapy seems to be promising as a treatment approach for persistent asthma in every day clinical practice.

Topics: Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Cross-Sectional Studies; Ethanolamines; Evidence-Based Practice; Female; Formoterol Fumarate; Hospitalization; Humans; Male; Middle Aged; Time Factors

Vitamin D is hypothesized to have some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid (ICS).. To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers (ICS or ICS plus long-acting β-agonist) on airway functions.. A randomized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period. Data on age, sex, body mass index, stage of asthma, serum total IgE, history of allergic rhinitis, atopic dermatitis, food allergy, and urticaria were collected. Spirometric parameters (forced expiratory volume in 1 second [FEV1] and ratio of FEV1 to forced vital capacity) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention. Patients were divided in 2 groups randomly. Both groups received asthma controllers (budesonide or budesonide plus formoterol) according to their stage, but the intervention group received vitamin D supplementation (100,000-U bolus intramuscularly plus 50,000 U orally weekly) in addition to asthma controllers.. FEV1 improved significantly in both groups after 8 weeks, but no significant difference was found between the 2 groups at baseline (P = .20) or after 8 weeks (P = .99); however, a significant improvement was seen in the intervention group in the last 16 weeks, and FEV1 was significantly better in the intervention group than the other group after 24 weeks (P < .001).. Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks.. irct.ir Identifier: IRCT201302079608N1.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dermatitis, Atopic; Dietary Supplements; Drug Synergism; Ethanolamines; Female; Food Hypersensitivity; Forced Expiratory Volume; Formoterol Fumarate; Humans; Immunoglobulin E; Iran; Male; Middle Aged; Prospective Studies; Rhinitis, Allergic; Urticaria; Vital Capacity; Vitamin D; Young Adult

The aim of this study was to compare lung deposition and assess the bioequivalence of two formulations containing budesonide and formoterol and being delivered via Elpenhaler and Turbuhaler, respectively. A pharmacokinetic (PK) study was conducted.. An open, randomized, two-sequence, two-period, crossover, single-dose study in 100 asthmatic patients under fasting conditions was performed. Wash out period was 6 days. Equivalence in lung deposition was assessed after a single inhalation of each treatment with concomitant oral administration of activated charcoal (40 g) to prevent gastrointestinal absorption of the drugs. Several PK parameters were estimated, the area under the drug concentration in plasma versus time curve (AUC0-t ) and the maximum drug concentration in plasma (Cmax ) being the primary response variables. Equivalent lung deposition was concluded if the 90% confidence interval (CI) for the Elpenhaler/Turbuhaler geometric mean ratio of AUC0-t and Cmax , for both drug substances fell within the regulatory limits (0.80-1.25).. Acceptance criteria were met. Equivalent lung deposition can be concluded. No statistically significant differences between treatments in the incidence of adverse events were found.. The formulations are bioequivalent regarding both rate and extent of absorption. The treatments were also well tolerated by the participating subjects.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Female; Formoterol Fumarate; Humans; Lung; Male; Middle Aged; Therapeutic Equivalency; Tissue Distribution; Young Adult

In a double-blind, placebo-controlled trial (EudraCT identifier: 2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated.. The trial included 604 subjects, ≥14 years, with mild-moderate HDM allergic asthma. Subjects were randomised 1:1:1:1 to 1, 3 or 6 SQ-HDM or placebo once daily. The primary endpoint was reduction in inhaled corticosteroid (ICS) after one year. ICS reduction, asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ) score was analysed post hoc in a subgroup with daily ICS use of 400-800 μg and ACQ score of 1-1.5, corresponding to partly controlled asthma (N = 108).. The trial met its primary endpoint. In the subgroup, the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 μg (p < 0.0001), while it was 0.52 (p = 0.010) for AQLQ. The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population (ICS reduction: p < 0.001); AQLQ: p = 0.044).. In this subgroup, including only patients with partly controlled asthma, the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population, both in terms of increased asthma control and improved quality of life.

Topics: Adult; Animals; Asthma; Budesonide; Double-Blind Method; Glucocorticoids; Humans; Pyroglyphidae; Quality of Life; Sublingual Immunotherapy; Surveys and Questionnaires; Tablets; Treatment Outcome

Even in stable asthma patients, acinar ventilation distribution can be abnormal, and we aimed to specifically maximize its reversibility by switching patients from a standard inhaled corticosteroid (iCS) to a fine particle iCS formulation.. For this prospective double-blind double-dummy randomized study, 66 stable asthma patients under maintenance iCS (equivalent budesonide ≤ 800 μg/day) were screened for abnormal baseline acinar ventilation heterogeneity (Sacin). After a 3-week run-in period, 35 eligible patients were randomized to fine particle beclomethasone (HFA-BDP; Qvar Autohaler) or to budesonide (DPI-BUD; Pulmicort Turbohaler). Asthma Control Test (ACT) score and various lung function indices reflecting the small airways were obtained at baseline, after 6 and 12 weeks.. Thirty one patients [age:52 ± 17(SD) years; FEV1:76 ± 19(SD)%pred] completed the study (DPI-BUD:n = 16; HFA-BDP:n = 15). After 6 and 12 weeks, there were no significant changes in acinar or conductive ventilation heterogeneity, nor in mid-expiratory flow, RV/TLC, closing capacity, impulse oscillometry indices (resistance, reactance), bronchial NO production or alveolar NO, in either treatment arm. Asthma control was maintained in both arms.. In stable asthma patients with small airways dysfunction under maintenance therapy, there is a residual functional abnormality in the lung periphery which is probably not eosinophilic in origin and cannot be normalized with the iCS formulations under study. ISRCTN17195095.

Topics: Acinar Cells; Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Prospective Studies; Vital Capacity

This study was done to determine the effects and outcome of inhaled budesonide in addition to standard management of asthma exacerbations in pediatric age groups. A randomized, double-blind, placebo controlled trial was done in a tertiary care urban hospital. Sixty six children aged 5 to 15 years with moderate to severe asthma exacerbations were eligible. All patients received a single dose of prednisolone 1mg/kg orally as first dose of systemic corticosteroids and then salbutamol (0.15mg/kg) and ipratropium bromide (500mcg) was nebulized every 20 minutes for 3 doses and then hourly for 2 hours as a part of standard treatment of asthma exacerbations. The intervention was 2mg (4mL) of budesonide or 4mL of normal saline which was nebulized immediately after the 1st dose of nebulized salbutamol and ipratropium bromide. The baseline characteristics of the budesonide group (n=33) and placebo group (n=33) were similar, but at 1 hour, 2 hour and 3 hour PEFR, respiratory rate, pulse rate, SaO2 and asthma score were significantly improved in the budesonide group compared to placebo group (p<0.01). The positive immediate effect of nebulized budesonide added to standard treatment of asthma exacerbations is an encouraging finding for further investigations of its routine use in the treatment of asthma exacerbations in children.

Topics: Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

The use of budesonide/formoterol in a single inhaler for both maintenance and reliever therapy is a recommended option for treatment of persistent asthma not responding well to inhaled corticosteroid (ICS) alone.. This was a multi-centre open-label study on patients whose asthma condition remained inadequately controlled by various asthma treatments other than budesonide/formoterol. After a 2-week run-in period, eligible patients underwent a 12-week treatment period with budesonide/formoterol (Symbicort SMART(®), 160/4.5 μg) twice daily plus as needed. Patient's asthma control and quality of life were assessed using the 5-item Asthma Control Questionnaire (ACQ-5) and the standardized Asthma Quality of Life Questionnaire (AQLQ-S), respectively.. A total of 862 eligible asthma patients who have had asthma for a mean duration of 10.73 ± 12.03 years entered a 12-week treatment with budesonide/formoterol maintenance and reliever therapy. During treatment, ACQ-5 score improved significantly by 0.58 ± 0.93 (95% CI, 0.51 to 0.64, P < 0.0001) from the baseline level of 1.62 ± 1.00. AQLQ(S) score improved by 0.70 ± 0.89 (95% CI, 0.64 to 0.76, P < 0.0001) from baseline. Asthma symptom score was also reduced significantly (P < 0.0001); between run-in and treatment periods, night- and day-time symptom scores were reduced by 0.32 ± 0.54 (95% CI, 0.28 to 0.35) and 0.30 ± 0.52 (95% CI, 0.27 to 0.34), respectively. The percentage of nights with awakenings due to asthma symptoms was reduced by 11.09 ± 26.13% (95% CI, 9.34 to 12.85%), while the percentage of asthma-control and symptom-free days increased by 20.90 ± 34.40% (95% CI, 18.59 to 23.21%) and 23.89 ± 34.62% (95% CI, 21.56 to 26.21%), respectively (P < 0.0001). Together with the improvement in asthma control, the number of night- and day-time inhalations of as-needed reliever medication decreased by 0.30 ± 0.82 (95% CI, 0.24 to 0.35) inhalations and 0.30 ± 0.97 (95% CI, 0.23 to 0.36) inhalations, respectively (P < 0.0001). No unexpected adverse events were reported.. During treatment of inadequately controlled asthmatic patients with budesonide/formoterol maintenance and reliever therapy, significant improvement in patients' asthma control and reductions in asthma symptoms and as-needed medication use was observed. Patients' quality of life was improved and the treatment was well tolerated.. ClinicalTrial.gov: (NCT00939341).

Topics: Adult; Asia; Asthma; Bronchodilator Agents; Budesonide; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Quality of Life; Sleep; Surveys and Questionnaires; Treatment Outcome

Objective measures are required that may be used as a proxy for exacerbations in asthma. The aim was to determine the sensitivity and specificity of electronic diary data to detect severe exacerbations (SEs) of asthma. A secondary aim was to identify phenotypic variables associated with a higher risk of exacerbation.. In the BIOAIR study, 169 patients with asthma (93 severe (SA); 76 mild to moderate (MA)) recorded lung function, symptoms and medication use in electronic diaries for 1 year. Data were analysed using receiver-operator characteristics curves and related to physician-diagnosed exacerbations. Medical history and baseline clinical data were used to assess risk of exacerbation.. Of 122 physician-diagnosed exacerbations, 104 occurred in the SA group (1.1 per patient/year), 18 in the MA group (0.2 per patient/year) and 63 were severe using American Thoracic Society/European Respiratory Society criteria. During exacerbations, peak expiratory flow (PEF) and forced expiratory volume in 1 s significantly decreased, whereas day and night symptoms significantly increased. An algorithm combining a 20% decrease in PEF or a 20% increase in day symptoms on 2 consecutive days was able to detect SEs with 65% sensitivity and 95% specificity. The strongest risk factors for SEs were low Asthma Control Questionnaire score, sputum eosinophils ≥ 3%, body mass index >25 and low quality of life (St George's Respiratory Questionnaire), with ORs between 3.61 and 2.22 (p<0.05).. Regular electronic monitoring of PEF and asthma symptoms provides an acceptable sensitivity and specificity for the detection of SEs and may be suitable for personal internet-based monitoring of asthma control.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Disease Progression; Drug Therapy, Combination; Electronic Health Records; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prognosis; Prospective Studies; Quality of Life; Sensitivity and Specificity; Surveys and Questionnaires; Time Factors; Young Adult

Inhaled glucocorticoids and long acting β2 -agonists reduce airway inflammation. It is unclear if this effect is based on the local action of the drugs or is due to a systemic effect on circulating peripheral blood lymphocytes. We assessed whether inhaled budesonide and/or formoterol modify the activity of circulating peripheral blood lymphocytes.. Placebo controlled crossover design, including healthy (n = 10) or mild asthmatic males (n = 8). Blood was collected in the morning at 08:00 before drug inhalation, and drugs (placebo, budesonide 400 μg, formoterol 12 μg) were inhaled alone or in combination at 08:30. Four more blood samples were collected after inhalation at 09:00, 09:30, 12:30 and at 09:30 am on the following day. The activity of the glucocorticoid receptor, NFκB and IκB was determined in isolated lymphocytes. Lymphocytes were stimulated with lipopolysaccharide (LPS 10 μg/mL) for 24 h and interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, eotaxin level were determined. Lymphocyte proliferation was induced by phytohaemagglutinin (PHA 10 μg/mL) over 24 h.. When combined, the drugs synergistically activated the glucocorticoid receptor within 30 min but did not modify NFκB or IκB activity. Inhaled budesonide significantly reduced LPS-induced IL-1β, IL-6, IL-8 and TNF-α secretion, while inhaled formoterol had no such effect; however when combined, the inhibitory effect of budesonide was significantly increased by formoterol. PHA-induced proliferation was reduced by both drugs alone and in combination.. Combined budesonide and formoterol may reduce airway inflammation and immune reactivity of circulating lymphocytes through its local and systemic effects.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Cytokines; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Lipopolysaccharides; Lymphocytes; Male; NF-kappa B; Time Factors; Treatment Outcome

Administration of the combination of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is the main treatment strategy for bronchial asthma. The ICS/LABA dosage can be reduced (stepped down) when the patient's symptoms and lung functions are well-controlled. In this study, we obtained fractional exhaled nitric oxide (FeNO) measurements to clarify whether the anti-inflammatory effect of budesonide/formoterol is shortened by step-down.. Fifty-four patients who visited the Kawasaki Medical School Hospital with newly diagnosed asthma from November 2008 to July 2010 received budesonide/formoterol for 8 weeks or more. In 29 patients, the forced expiratory volume in 1 s% predicted increased to 80% or more, and the Asthma Control Questionnaire (ACQ) score decreased to 0.5 or less within 12 weeks. These 29 patients were randomly divided into two groups: the dosage-continued group (n = 14) and the step-down group (n = 15). Then, the impact of budesonide/formoterol step-down on ACQ score, pulmonary function and FeNO level was compared between the groups.. In the step-down group, the dosage was stepped down from 538 mcg/day to 331 mcg/day. In both groups, pulmonary function indicators and symptoms did not change. However, the mean FeNO level decreased significantly in the dosage-continued group (from 50.9 ppb to 45.0 ppb), and increased significantly in the step-down group (from 51.0 ppb to 65.7 ppb).. Clinicians should be more careful when stepping down budesonide/formoterol based solely on patients' symptoms and/or pulmonary function.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Breath Tests; Budesonide; Drug Combinations; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Middle Aged; Nitric Oxide; Quality of Life; Statistics, Nonparametric; Surveys and Questionnaires

The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood.. We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts.. Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program. Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs.. A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%). Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%).. Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Female; Forced Expiratory Volume; Humans; Male; Nedocromil; Sensitivity and Specificity

A comparative investigation was conducted to study the therapeutic effect of using two powder inhalers (the new-generation device--an easyhaler as well as an aerolyser inhaler) in daily practice for treating patients with moderate asthma. It showed the pharmacological equivalence, efficiency, and safety of applying a combination of the easyhalers budesonide and formoterol, as well as the simplicity and convenience to use the inhalers of this type.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Dry Powder Inhalers; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Young Adult

In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it.. We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders".. On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/μL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04).. Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; C-Reactive Protein; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Particle Size; Quality of Life; Spirometry; Statistics, Nonparametric; Treatment Outcome

Achievement and maintenance of good asthma control is a major objective in asthma management. However, asthma control in many patients is suboptimal, due to improper use of asthma medications and non-adherence. The aim of this study was to evaluate the effect of a pharmacist intervention on asthma control in adult patients.. A 6-month cluster randomized controlled trial was undertaken with allocation of community pharmacies to intervention or control group. Adult asthma patients in the intervention group received a protocol-based intervention addressing individual needs related to asthma control, inhaler technique and medication adherence. Patients in the control group received usual care. Main variables were measured at baseline, 3 and 6 months.. 336 patients completed the study, 150 in the control group and 186 in the intervention group. The intervention resulted in enhanced asthma control: Patients receiving the intervention had an Odds ratio of 3.06 (95% CI:1.63-5.73; p < 0.001) of having controlled asthma six months later. In the intervention group mean ACQ scores significantly improved [0.66 points (SD: 0.78); p < 0.001] and the number of controlled asthma patients increased by 30.1% (p < 0.001) after 6 months. The intervention also resulted in improved medication adherence (by 40.3%, p < 0.001) and inhaler technique (by 56.2%, p < 0.001). No significant changes for any of these variables were observed in the control group.. The AFasma study focused on the important outcomes of asthma management, and showed that through the designed intervention, community pharmacists can increase controlled asthma patients compared to usual care. Trial registration NCT01085474.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cluster Analysis; Community Pharmacy Services; Drug Combinations; Ethanolamines; Female; Humans; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Patient Education as Topic; Treatment Outcome; Young Adult

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 μg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 μg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. (. ISRCTN60408425).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome; Young Adult

To explore the therapeutic efficacies of inhaled corticosteroids (ICS) plus low-dose theophylline for moderate bronchial asthma.. A total of 280 patients with moderate bronchial asthma at People's Hospital of Zhengzhou University between January 2011 and December 2011 were recruited and randomized into 2 groups: observation group with inhaled budesonide 400 µg/d plus aminophylline tablet (0.1 g, 3 times/day, oral administration and control group with inhaled budesonide 320 µg/day plus formoterol 9 µg/day. The course of treatment was around 6 months. The forced expiratory volume in one second % predicted (FEV1% predicted), interleukin (IL)-4, IL-5 and IgE of peripheral blood were compared before and after treatment.. Before and 6 months after treatment, the values of FEV1 % predicted, IL-4, IL-5 and IgE for the observed group were 68% ± 6% and 76% ± 6%, (14.5 ± 4.4) and (7.2 ± 2.6) ng/L, (27.4 ± 6.2) and (24.2 ± 5.9) ng/L, (771 ± 130) × 10(3) and(592 ± 104) × 10(3) U/L, respectively, while those for the control group were 66% ± 8% and 77% ± 6%, (13.7 ± 4.3) and (7.7 ± 4.0) ng/L, (26.9 ± 5.8) and (24.6 ± 4.8) ng/L, (752 ± 154) and (604 ± 122) × 10(3) U/L, respectively. There were significant improvements in both groups (all P < 0.05). No differences existed between two groups (all P > 0.05).. Compared with ICS plus inhaled long-acting β2-agonists (LABA), ICS plus low-dose theophylline shows similar efficacies in the improvement of lung function and the control of airway inflammation for asthmatics.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aminophylline; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Immunoglobulin E; Interleukin-4; Interleukin-5; Male; Middle Aged; Theophylline

This non-interventional real-life study (NCT00884689) compared budesonide/formoterol (Symbicort®) maintenance and reliever therapy (SMART™) with a free combination of inhaled corticosteroid (ICS) + long-acting β2-agonist (LABA) (in separate inhalers) and as-needed short-acting β2-agonist (SABA) in adult asthma patients with an exacerbation in the past 24 months.. Asthma patients received SMART™ or free-combination ICS + LABA and as-needed SABA for 6 months. Allocation of patients and doses prescribed were at physician's discretion. No other restrictions applied. Primary endpoint: mean no. of rescue medication puffs/day.. 482 patients were included (SMART™ n = 310; free combination n = 172). SMART™ patients used less rescue medication vs the free-combination group (mean difference - 0.27 puffs/day; p = 0.013). Severe asthma exacerbations were rare (mean rate 0.20 vs 0.17/year for SMART™ vs free combination). The mean ICS dose was 615 µg in SMART™ and 678 µg in free-combination group.. In this real-life setting, SMART™-treated patients used less rescue medication despite a lower ICS burden vs conventional asthma management with three different inhalers.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Azides; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Germany; Humans; Male; Middle Aged; Prevalence; Quality of Life; Risk Factors; Self Administration; Serotonin; Treatment Outcome

The efficacy of inhaled corticosteroids (ICS) in asthma exacerbation are yet to be clarified. The aim of this study was to investigate the efficacy of nebulized ICS in children with moderate-to-severe acute exacerbation of asthma in an emergency room setting in order to elucidate the potential use of ICS as the first-line therapy in the management of acute exacerbation of asthma.. This was a prospective, randomized, double-blind, placebo-controlled study. Paediatric patients with moderate-to-severe acute exacerbation of asthma in emergency room were randomized to receive nebulized salbutamol and ipratropium bromide, with the addition of nebulized high-dose budesonide (BUD group, n = 60) or normal saline (control group, n = 58), three doses in the first hour.. The improvement in forced expiratory volume in 1 s was similar in both groups at 0 h after three doses of nebulization, but there was significantly further improvement at 1 and 2 h in the BUD group (0.095 ± 0.062 L and 0.100 ± 0.120 L, respectively) compared with the control group (0.059 ± 0.082 L and 0.021 ± 0.128 L, respectively), P = 0.013 and 0.001, respectively. Complete remission rate was significantly higher (84.7% vs 46.3%, P = 0.004) and need for oral corticosteroids was significantly lower (16.9% vs 46.3%, P = 0.011) in BUD group than in control group.. On the basis of nebulized short-acting bronchodilators, addition of nebulized high-dose budesonide resulted in clinical improvement in children with moderate-to-severe acute exacerbation of asthma, suggesting that nebulized high-dose ICS can be used as first-line therapy for non-life-threatening acute exacerbation of asthma in children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asian People; Asthma; Budesonide; Child; China; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Prospective Studies; Severity of Illness Index; Treatment Outcome

Procaterol, a selective, short-acting beta-2 adrenoceptor agonist, is effective in treating 'classical' asthma, but its efficacy for cough-variant asthma (CVA) is unknown. We evaluated the efficacy and safety of procaterol combined with budesonide for CVA.. A prospective, randomized, double-blind, placebo-controlled, multicenter trial in China was conducted. One hundred and fifty-nine patients diagnosed with CVA (aged 18-75 years) were randomly divided into two groups to receive twice daily for 8 weeks, inhaled budesonide 100 μg plus either oral procaterol 25 μg or placebo. Primary and secondary efficacy variables were cough symptom severity scores and Leicester Cough Questionnaire (LCQ) life quality scores. Adverse events were also assessed.. The budesonide/placebo and budesonide/procaterol groups contained 80 and 78 participants (one excluded for later diagnosis of eosinophilic bronchitis), respectively, with similar baseline characteristics. Daily cough score declined during treatment in both groups and was lower in the budesonide/procaterol group at 8 (0.44 vs 0.73) and 10 (0.36 vs 0.69) weeks (P < 0.05). Compared with the budesonide/placebo group, the proportion of patients with a reduction of 3 points or greater (66% vs 42%) and that of patients scoring 0 points (63% vs 51%) was higher in the budesonide/procaterol group for daily cough scores (P < 0.05). At 8 weeks, LCQ score improvement was superior in the budesonide/procaterol group (38.94 ± 19.24 vs 32.71 ± 18.92; P < 0.05).. Procaterol combined with budesonide was well tolerated and effective at improving cough symptoms and quality of life in patients with CVA.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; China; Comorbidity; Cough; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Procaterol; Prospective Studies; Treatment Outcome; Vital Capacity

Budesonide inhalation suspension (BIS) and montelukast provide acceptable asthma control, whereas overall measures favored BIS in children aged 2 to 8 years with mild persistent asthma.. We compared BIS and montelukast over a 1-year period in children aged 2 to 4 years with asthma.. Data were derived from a 52-week, open-label, randomized, active-controlled, multicenter study (NCT00641472). Children with mild asthma received either BIS 0.5 mg or montelukast 4 to 5 mg once daily. Patients were stepped up to twice-daily BIS or oral corticosteroids for mild or severe asthma worsening, respectively. Primary efficacy assessment was time to first additional asthma medication for exacerbation over 52 weeks.. Two hundred two patients, age 2 to 4 years, received BIS (n = 105) or montelukast (n = 97). No difference was observed between the BIS and montelukast groups in median time to first additional asthma medication over 52 weeks (183 vs 86 days). Statistically significant differences were observed in favor of BIS over montelukast in the percentage of patients requiring oral steroids at 52 weeks (21.9% vs 37.1%; P = .022), the rate (number/patient/year) of additional courses of medication (1.35 vs 2.30; P = .003), the rate of additional oral steroid therapy (0.44 vs 0.88; P = .008), and caregivers' ability to manage the patient's symptoms (P = .026). Both treatments were well tolerated.. BIS and montelukast provided acceptable asthma control in children aged 2 to 4 years with mild persistent asthma with no significant difference between treatments in the primary end point; however, several secondary outcomes showed statistically significant differences (and many had numerical differences) in favor of BIS over montelukast.

Topics: Acetates; Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child, Preschool; Cyclopropanes; Drug Administration Schedule; Female; Humans; Male; Quinolines; Sulfides; Suspensions; Treatment Outcome

The Single combination budesonide-formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients, but whether the high doses of corticosteroid and β agonist increase the risk of adverse effects with both short-term and cumulative exposure is not certain. Our aim was to investigate whether the SMART regimen would reduce the risk of overuse of β agonist, reduce the likelihood of patients to seek medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid.. In this 24-week trial undertaken at four primary health-care practices and one hospital in New Zealand, patients (aged 16-65 years) with a recent asthma exacerbation were randomly assigned in a 1:1 ratio to the SMART or standard fixed-dose regimen. Treatment in the SMART group consisted of two actuations of budesonide-formoterol (200 μg and 6 μg, respectively, per actuation) twice daily, delivered through a combination metered dose inhaler (MDI), with one extra actuation as needed for relief of symptoms; treatment in the standard group consisted of two actuations of budesonide-formoterol (200 μg and 6 μg, respectively, per actuation) twice daily through a combination MDI with one to two actuations of salbutamol (100 μg per actuation) by MDI as needed for relief of symptoms. MDIs were monitored electronically to measure actual use of medication. The allocation sequence for randomisation was computer generated, with a block size of eight per site. Participants, investigators, and the statistician were not masked to group assignment. The primary outcome was the proportion of participants with at least one high-use episode of β agonist (more than eight actuations per day of budesonide-formoterol in addition to the four maintenance doses in the SMART group or more than 16 actuations per day of salbutamol in the standard group). Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000515099.. 303 patients were randomly assigned to the SMART (n=151) or standard group (n=152). No significant difference was noted between the SMART and standard groups in the proportion of participants with at least one high-use episode of β agonist (84 [56%] vs 68 [45%], respectively, relative risk 1·24 [95% CI 0·99-1·56]; p=0·058). There were fewer days of high use in the SMART group (mean 5·1 days [SD 14·3] vs 8·9 days [20·9], relative rate 0·58 [0·39-0·88]; p=0·01). Of the patients who had at least one high-use episode, those in the SMART group had fewer days of high use without medical review (8·5 days [17·8] vs 18·3 days [24·8], 0·49 [0·31-0·75]; p=0·001). The SMART regimen resulted in higher inhaled corticosteroid exposure (943·5 μg budesonide per day [1502·5] vs 684·3 μg budesonide per day [390·5], respectively; ratio of means 1·22 [1·06-1·41]; p=0·006), but reduced oral corticosteroid exposure (77·5 mg prednisone [240·5] vs 126·6 mg prednisone [382·1], respectively; p=0·011), with no significant difference in composite systemic corticosteroid exposure (793·7 mg prednisone equivalent per year [893·1] vs 772·1 mg prednisone equivalent per year [1062·7], respectively; 1·03 [0·86-1·22]; p=0·76). Participants in the SMART group had fewer severe asthma exacerbations (35 [weighted mean rate per year 0·53] vs 66 [0·97]; relative rate 0·54 [0·36-0·82]; p=0·004).. The SMART regimen has a favourable risk-to-benefit profile and can be recommended for use in adults at risk of severe asthma exacerbations.. Health Research Council of New Zealand.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Hospitalization; Humans; Male; Middle Aged; Risk Factors; Treatment Outcome

To analysis the clinical characteristics of children with cough variation asthma (CVA) who received treatments with Carboxymethl starch sodium solution and inhaled Glucocorticoid budesonide.. A total of 96 children with CVA were divided into two group randomly. The control group (n = 49) received inhaled budesonide treatment (500 microg/times in 1-5 years old children, 1 mg/times and 2 times/day in 6-14 years old children over a 12 week period). The children in treatment group (n = 47) were given carboxymethl starch sodium solution (3 mL/times in 1-3 years old children, 5 mL/times in 4-7 years old children, 7 mL/times in 8-14 years old children, 3 times/day) in addition to the inhaled budesonide treatment. Observations were made on clinical therapeutic effects, cough score and the level of IgE 4 weeks, 8 weeks and 12 weeks after the treatments, respectively. Recurrence rate and adverse reactions were investigated.. Compared with the control group, the treatment group had significantly improved clinical characteristics after 8 weeks and 12 weeks of treatments (P < 0.05), and reduced cough scores after 4 weeks, 8 weeks and 12 weeks of treatments (P< 0.05). The IgE level of the children in the treatment group was significantly lower than the controls after 12 weeks of treatments (P < 0.05). The treatment group also had significantly lower recurrence rate and adverse reactions than the controls (P < 0.05).. Carboxymethl starch sodium solution can boost the clinical efficiency of inhaled budesonide in the treatment of children with cough variant asthma. It is safe and effectual.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cough; Drug Therapy, Combination; Female; Humans; Infant; Male; Solutions; Starch

Combinations of inhaled corticosteroids (ICS) and inhaled long-acting beta(2)-agonists (LABA) have become widely used for the initiation of maintenance treatment for asthma. However, it has not been fully elucidated whether ICS/LABA alters the time-course of different control outcome measures in steroid-naive patients with asthma compared to the treatment with ICS alone. We compared the time-response in Asthma Control Questionnaire (ACQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide fraction (FE(NO)), and airway responsiveness to methacholine (PD(200)) between budesonide (BUD) and budesonide/formoterol (BUD/FM). BUD/FM therapy significantly improved the ACQ score at week 2 and week 4 (p < 0.01 and p < 0.05), and increased FEV1 and the methacholine threshold at week 8 and week 24 (all p < 0.05) compared to BUD alone. A logistic function model showed that the BUD/FM combination significantly improved ACQ, FEV1, FE(NO) and PD(200) at a faster rate than BUD over 24 weeks (p < 0.001 for ACQ, FEV1, PD(200), and p < 0.05 for FE(NO), z-test). A significant variance in the time-response was also found in the outcomes of the two treatment groups (FE(NO) and ACQ > FEV1 and PD(200), p < 0.001, z-test). The present study provides evidence that ICS/LABA combination therapy results in a more rapid improvement in asthma symptoms, lung function, and airway inflammation compared to ICS monotherapy in steroid-naive patients with asthma.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Nitric Oxide; Prospective Studies

To evaluate the efficacy and tolerability of budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline in adults with persistent asthma not adequately controlled with inhaled corticosteroid (ICS) therapy alone.. In this 12-month, randomized, double-blind, parallel-group, phase III study (NCT00839800), patients (age ≥ 16 years; receiving maintenance ICS; ≥ 1 severe exacerbation in the 12 months prior to study entry) were randomized to either budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus budesonide/formoterol 160/4.5 μg as-needed or budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus terbutaline 0.4 mg as-needed for 12 months.. time to first severe asthma exacerbation; secondary outcomes included: lung function, asthma symptom variables and tolerability.. Two thousand and ninety-one patients were randomized: 170 (16%) receiving budesonide/formoterol maintenance and reliever therapy experienced 259 severe exacerbations versus 229 patients (22%) receiving budesonide/formoterol plus terbutaline who experienced 363 severe exacerbations. Budesonide/formoterol maintenance and reliever therapy prolonged the time to first severe exacerbation versus budesonide/formoterol plus terbutaline (P = 0.0007) and reduced the instantaneous risk of an exacerbation by 30% (hazard ratio 0.70, 95% confidence interval 0.57-0.85, P = 0.0003). Times to first oral steroid use, first hospitalization and first emergency room treatment were all significantly prolonged in the budesonide/formoterol maintenance and reliever group versus budesonide/formoterol plus terbutaline. Both treatment groups were well tolerated.. Budesonide/formoterol maintenance and reliever therapy provided more effective asthma control, including a prolonged time to first severe asthma exacerbation, than budesonide/formoterol plus terbutaline and was well tolerated. Budesonide/formoterol maintenance and reliever therapy also improved lung function and asthma symptoms.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Longitudinal Studies; Lung; Male; Middle Aged; Terbutaline; Treatment Failure; Treatment Outcome

Spacers and valved holding chambers (VHCs) were developed to facilitate using pressurized metered dose inhaler (pMDI) by patients who could not coordinate the actions required for successful pMDI use. There is little in vivo evidence about how VHC may affect the bronchodilation from combination drugs in pMDI. This study was to determine the effect, if any, of VHC on the bronchodilating actions of the pMDI budesonide/formoterol combination.. Sixteen adult asthmatic subjects with 15% or greater reversibility of forced expiratory volume in one second (FEV-1), 15 minutes after inhaling 180-360 μg of albuterol, participated. The study had a randomized crossover design with each subject using budesonide-formoterol pMDI as described in the product information one timeand on a second occasion using the pMDI with a VHC. Spirometry and impedance osscilometry were measured at baseline and repeatedly over a 12-hour period. This study was approved by IntegReview Institutional Review Board, Austin, TX, USA. The clinical trial number for this study was NCT 009-15538 (http://www.westernskymed.com).. The area under the curve of FEV-1, the FEV-1, and the fraction FEV-1/FVC was similar over the 12-hour time frame with both methods. Resistance was not different at any time point. In both procedures, the onset of bronchodilation occurred rapidly within 3 to 5 minutes.. In well-trained asthmatic subjects, both tested methods caused equivalent bronchodilation. This suggests a VHC itself has no deleterious effect on the bronchodilator activity in the combined drug. These results may not apply to patients who have coordination problems with the pMDI and further study is indicated.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Drug Combinations; Ethanolamines; Female; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Spirometry

Budesonide (22(R,S)-16α,17α-butylidenedioxy-11β,21-dihydroxypregna-1,4-diene-3,20-dione) (BUD) is a glucocorticoid widely used for the treatment of asthma and rhinitis. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes, but its use by other routes (eg, inhalation) is allowed. The objective of this study was to evaluate the urinary profiles of different metabolites of BUD after oral and inhaled administrations in order to define a criterion to discriminate between forbidden and authorized administrations of the drug.. A liquid chromatography-tandem mass spectrometry method was validated to quantify BUD, 16α-hydroxy-prednisolone, 6β-hydroxy-budesonide, and 6α-hydroxy-budesonide and to qualitatively determine 13 additional BUD metabolites. The method was applied to urine samples collected in clinical studies where BUD was administered to healthy volunteers by the oral route (n = 2) and by inhalation for 3 consecutive days followed by a single oral dose (n = 8).. Reporting levels of the different metabolites were evaluated in terms of specificity (no false-positive results after inhalation) and sensitivity (no false-negative results after oral intake).. Taking into consideration the administered doses, the best compromise to discriminate between authorized inhaled administration and forbidden oral intake of BUD was found using a reporting level of 20 ng/mL of metabolite 6β-hydroxy-budesonide.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Chromatography, Liquid; Cross-Over Studies; Glucocorticoids; Humans; Male; Sensitivity and Specificity; Sports; Tandem Mass Spectrometry

The use of budesonide/formoterol as both maintenance and reliever therapy in asthma is recommended in many countries; however, there are limited data available for the Asian patient population.. This was a randomized, double-blind, crossover, active comparator-controlled, phase III study. Patients aged 16-65 years with persistent asthma received either budesonide/formoterol 160 mg/4.5 mg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 μg/4.5 mg one inhalation twice daily as maintenance treatment. After a 7- to 14-day washout period, patients crossed over to receive the other medication for a further 3 days. Adverse events (AEs), clinical laboratory variables, 12-lead electrocardiogram (ECG) and vital signs were assessed throughout.. Twenty-five patients (mean age 44.3 years, 40% female) were randomized and received at least one dose of study medication. Overall, 14 AEs were reported in 12 out of 25 patients (48%) during high-dose budesonide/ formoterol therapy and 24 AEs were reported in 14 out of 23 patients (61%) during terbutaline therapy. The majority of AEs were mild in intensity and no serious AEs were reported. The most common AEs were tremor (12%) during budesonide/formoterol therapy and tremor (17%), palpitations (13%), tachycardia (13%) and decreased serum potassium (13%) during terbutaline therapy. There were no clinically significant differences from baseline or between groups in laboratory values, vital signs or ECG recordings.. Budesonide/formoterol 160 μg/4.5 mg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 μg/4.5 μg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Young Adult

Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.. Bronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.. Compared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.. Expression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Allergens; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cell Line, Tumor; Cross-Over Studies; Dual Specificity Phosphatase 1; Epithelial Cells; Gene Expression; Humans; Lung; Myocytes, Smooth Muscle; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tacrolimus Binding Proteins; Transcription Factors

The management of asthma has changed since the introduction of budesonide/formoterol (Symbicort®) as both maintenance and reliever therapy (SMART). SMART and its effects on bronchial hyperresponsiveness (BHR) have not been studied in primary care.. To compare the effects of SMART and guideline-driven usual care (UC) on BHR and clinical asthma severity in primary care practice.. Patients with mild-to-moderate stable asthma were randomised to receive SMART treatment (n=54) (budesonide/formoterol 80/4.5 μg Turbuhaler®, two puffs once daily and extra inhalations as needed) or UC treatment (n=48) for 12 months. Diary data, Asthma Control Questionnaire scores, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) measurements were collected during run-in and after 1, 3, 6, and 12 months of treatment. BHR, measured as the dose of histamine provoking a fall in FEV1 of 20% (PD20-histamine), was determined at randomisation and after 12 months.. One hundred and two patients with asthma participated in the study. The change in PD20-histamine during the study was not significantly different between the SMART and UC groups (p=0.26). The mean inhaled corticosteroid (ICS) dose was 326 μg beclomethasone dipropionate (BDP) equivalents/day (95% CI 254 to 399) with SMART, which was significantly lower (p<0.0001) than the mean ICS dose with UC treatment (798 μg BDP equivalents/day (95% CI 721 to 875). Morning and evening PEF values increased significantly with SMART treatment compared with UC; FEV1, symptoms and asthma control did not differ.. Despite a 59% lower dose of ICS, BHR and other clinical outcomes remained stable during SMART treatment while PEF values improved.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Histamine; Histamine Agonists; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Practice Guidelines as Topic; Primary Health Care; Severity of Illness Index; Treatment Outcome

The use of budesonide/formoterol as both maintenance and reliever therapy in asthma is recommended in many countries; however, there are limited data available for the Asian patient population.. This study aimed to evaluate the short-term safety and tolerability of a fixed high-dose combination of the inhaled corticosteroid budesonide and the long-acting β(2)-adrenoceptor agonist formoterol with that of the β(2)-agonist terbutaline for acute symptom relief in Japanese adults with persistent asthma who were already receiving a combination of budesonide/formoterol maintenance therapy.. This was a randomized, double-blind, crossover, active comparator-controlled, phase III study. Patients aged 16-65 years with persistent asthma received either budesonide/formoterol 160 μg/4.5 μg ten inhalations daily for 3 days via Turbuhaler® or terbutaline 0.4 mg ten inhalations daily for 3 days via Turbuhaler®, in addition to budesonide/formoterol 160 μg/4.5 μg one inhalation twice daily as maintenance treatment. After a 7- to 14-day washout period, patients crossed over to receive the other medication for a further 3 days. Adverse events (AEs), clinical laboratory variables, 12-lead electrocardiogram (ECG) and vital signs were assessed throughout.. Twenty-five patients (mean age 44.3 years, 40% female) were randomized and received at least one dose of study medication. Overall, 14 AEs were reported in 12 out of 25 patients (48%) during high-dose budesonide/formoterol therapy and 24 AEs were reported in 14 out of 23 patients (61%) during terbutaline therapy. The majority of AEs were mild in intensity and no serious AEs were reported. The most common AEs were tremor (12%) during budesonide/formoterol therapy and tremor (17%), palpitations (13%), tachycardia (13%) and decreased serum potassium (13%) during terbutaline therapy. There were no clinically significant differences from baseline or between groups in laboratory values, vital signs or ECG recordings. conclusion: Budesonide/formoterol 160 μg/4.5 μg ten inhalations daily for 3 days in addition to ongoing budesonide/formoterol 160 μg/4.5 μg one inhalation twice daily maintenance therapy was well tolerated in Japanese adults with persistent asthma.. Clinicaltrials.gov identifier: NCT00837967; AstraZeneca study code: D589LC00003.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Japan; Middle Aged; Young Adult

Information comparing subjective and objective measurements of adherence to study medications and the effects of adherence on treatment-related differences in asthma clinical trials are limited.. We sought to compare subjective and objective measurements of children's adherence to inhaled corticosteroids or placebo and to determine whether adherence to study medications modified treatment-related differences in outcomes.. In an ancillary study conducted in 3 of 8 Childhood Asthma Management Program Clinical Centers, adherence was assessed by using self-reported and objective data in 5- to 12-year-old children with mild or moderate asthma who were randomly assigned to 200 μg of inhaled budesonide twice per day (n = 84) or placebo (n = 56) for 4 years. The κ statistic was used to evaluate agreement between self-reported adherence (daily diary cards) and objectively measured adherence (number of doses left in study inhalers). Multivariable analyses were used to determine whether adherence to study treatment modified treatment-related differences in outcomes.. Adherence of less than 80% was seen in 75% of 140 children when adherence was measured objectively but only in 6% of children when measured by means of self-report. There was poor agreement between objective and subjective measurements of adherence of at least 80% (κ = 0.00; 95% CI, -0.05 to 0.04); self-reported adherence over the 4-year period generally overestimated objectively measured adherence (93.6% vs 60.8%, P < .0001). There was little evidence to indicate that adherence modified treatment-related differences in outcomes.. Researchers should use objective rather than self-reported adherence data to identify clinical trial participants with low levels of adherence to study treatment.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Female; Humans; Male; Medication Adherence; Treatment Outcome

Studies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics.. EuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (Symbicort (®) Turbuhaler(®))(h) maintenance and reliever therapy (Symbicort SMART(®)) at two maintenance doses of budesonide/formoterol (160/4.5 μg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting β(2)-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a smoking history <10 pack-years if older), who were compared with a propensity-matched group of non-smokers. At baseline, smokers had lower post-bronchodilator peak expiratory flow, lower peak flow reversibility and used more reliever medication per day. Severe asthma exacerbations were counted and changes in five-item Asthma Control Questionnaire (ACQ-5) scores from baseline calculated.. There were 48 and 47 exacerbations in smokers and non-smokers, respectively. Mean time to first severe exacerbation was not statistically different between the two groups. The mean change in ACQ-5 score was significantly greater in non-smokers. Considering the two treatment options there was a statistically significant prolonged time to first severe exacerbation with 2 × 2 versus 1 × 2 in the smokers, but not in the non-smokers. In smokers, the reductions in ACQ-5 scores, asthma symptoms, use of as-needed medication and awakenings were also all significant in favour of 2 × 2 with similar or greater changes than in smokers treated with 1 × 2.. Asthmatic patients with a limited smoking history benefit from treatment with budesonide/formoterol maintenance and reliever therapy with dosing 2 × 2 being superior to 1 × 2.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Peak Expiratory Flow Rate; Smoking; Surveys and Questionnaires; Treatment Outcome

Concerns exist that responses to long-acting β(2)-adrenergic agonists in black patients may differ from the general population. The efficacy and safety of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (BUD DPI) were evaluated in adolescent and adult black asthma patients.. This 12-week, randomized, double-blind, multicenter, phase IV US study was conducted in 311 self-reported black patients aged ≥12 years with moderate to severe persistent asthma, previously receiving medium- to high-dose inhaled corticosteroid. After 2 weeks on BUD 90 μg × 2 inhalations twice daily (bid), symptomatic patients were randomized to BUD/FM 160/4.5 μg × 2 inhalations bid or BUD 180 μg × 2 inhalations bid.. Improvement in predose forced expiratory volume in 1 second from baseline to the treatment mean (primary variable) was greater with BUD/FM versus BUD (0.16 vs. 0.07 L; p = .008); this effect was also observed at weeks 2, 6, and end of treatment (p ≤ .032). Greater improvements (p < .001) in peak expiratory flow with BUD/FM versus BUD were seen at first measurement and maintained during 12 weeks (morning: 25.34 vs. 7.53 L/minute, respectively; evening: 21.61 vs. 7.67 L/minute, respectively); greater improvements in daily asthma symptom score and rescue medication use were also observed (p ≤ .039). Both treatments were well tolerated, with similar safety profiles.. In this population of black asthma patients, BUD/FM pMDI resulted in greater improvements in pulmonary function and asthma control versus BUD DPI, with similar safety profiles.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Black or African American; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Follow-Up Studies; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Multivariate Analysis; Reference Values; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; Young Adult

Combination therapy with inhaled corticosteroids and long-acting β(2)-agonists results in improved asthma symptom control compared with the use of inhaled corticosteroids alone. However, the effects of combination therapy on structural changes and inflammation of the airways are still unknown. The aim of this study was to compare the effects of budesonide/formoterol with those of budesonide alone on airway dimensions and inflammation in individuals with asthma.. Fifty asthmatic patients were randomized to treatment with budesonide/formoterol (200/6 µg, two inhalations bd) or budesonide (200 µg, two inhalations bd) for 24 weeks. Airway dimensions were assessed using a validated computed tomography technique, and airway wall area (WA) corrected for body surface area (BSA), percentage WA (WA%), wall thickness/Ösquare root BSA, and luminal area (Ai)/BSA at the right apical segmental bronchus, were measured. The percentage of eosinophils in induced sputum, pulmonary function, and Asthma Quality of Life Questionnaires (AQLQ) were also evaluated.. There were significantly greater decreases in WA/BSA (P < 0.05), WA% (P < 0.001) and wall thickness/square root BSA (P < 0.05), and increases in Ai/BSA (P < 0.05), in subjects treated with budesonide/formoterol compared with those treated with budesonide. The reduction in sputum eosinophils and increase in per cent of predicted forced expiratory volume in 1 s (FEV(1) %) were greater for subjects treated with budesonide/formoterol compared with those treated with budesonide alone. In the budesonide/formoterol group, the changes in WA% were significantly correlated with changes in sputum eosinophils and FEV(1%) (r = 0.84 and r = 0.64, respectively). There were improvements in the AQLQ scores after treatment with budesonide/formoterol.. Budesonide/formoterol combination therapy is more effective than budesonide alone for reducing airway wall thickness and inflammation in individuals with asthma.

Topics: Adult; Asthma; Bronchi; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Sputum; Tomography, X-Ray Computed

Previous studies have shown disparities between Black and Hispanic patients compared with other populations in response to asthma medications.. The aim of this analysis was to assess the effect of budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) and BUD on predefined criteria for asthma worsening, an asthma control metric generally aligned with definitions of moderate asthma exacerbations, across four different populations.. Data were from four 12-week, randomized, double-blind, US studies of BUD/FM pMDI treatment in patients aged 12 years or older with varying asthma severities and of varying races. Predefined asthma events and withdrawals due to predefined events were assessed as secondary study endpoints. Study I (NCT00651651) includes data from predominantly White patients with mild to moderate asthma who were randomized to BUD/FM pMDI 160/9 μg twice daily (bid; n = 123) or BUD pMDI 160 μg bid (n = 121). Study II (NCT00652002) includes data from predominantly White patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 124) or BUD pMDI 320 μg bid (n = 109). Study III (NCT00702325) included self-reported Black patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 153) or BUD dry powder inhaler 360 μg bid (n = 148). Study IV (NCT00419757) included self-reported Hispanic patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 127) or BUD pMDI 320 μg bid (n = 123). Patients were to be withdrawn from the studies if they developed an asthma event, as determined by predefined criteria, except for night-time awakenings, where withdrawal was left to the study physician's judgment.. Overall, fewer patients in the studies (study I, II, III, and IV, respectively) experienced ≥1 asthma event in the BUD/FM group (18.7%, 29.8%, 37.3%, 25.2%) versus the BUD group (21.5%, 44.0%, 45.3%, 31.7%); only study II results showed a statistically significant difference between treatments. Fewer patients with moderate to severe asthma (studies II, III, and IV) were withdrawn due to ≥1 asthma event in the BUD/FM group (10.5%, 11.8%, 3.1%, respectively) than in the BUD group (20.2%, 18.9%, 6.5%, respectively); however, percentages were similar in the BUD/FM (7.3%) and BUD (6.6%) groups in patients with mild to moderate asthma (study I).. Predefined asthma event rates were numerically or significantly lower for patients with asthma receiving BUD/FM pMDI versus BUD, regardless of race or disease severity. Differences between the BUD/FM pMDI and BUD groups were smaller in patients with mild to moderate asthma than in those with moderate to severe asthma, most likely because patients with milder disease had lower asthma event rates. Overall, these findings support the efficacy of BUD/FM pMDI in achieving asthma control in patients with moderate to severe asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Severity of Illness Index; Treatment Outcome

There are no published studies that have compared bronchodilatory effect of inhaled budesonide/formoterol combination with budesonide/salbutamol delivered by metered dose inhaler with a spacer in acute exacerbation of asthma in children. We, therefore, compared the bronchodilatory effects of inhaled budesonide/formoterol (dose: 200 μg and 12 μg respectively) combination with budesonide (200 μg)/salbutamol (200 μg) administered by metered dose inhaler and spacer in children of 5-15 years with mild acute exacerbation of asthma [Modified Pulmonary Index Score (MPIS) between 6-8] in this double-blind, randomized controlled trial. The primary outcome was FEV1 (% predicted) in the two groups at 1, 5, 15, 30, 60 min after administration of the study drug.. We did not observe any significant differences in the % predicted FEV1 and MPIS between formoterol and salbutamol at various time points from 1 min to 60 min post drug administration. There was significant improvement in FEV1 (% predicted) from baseline in both the groups as early as 1 min after drug administration.. Salbutamol or formoterol delivered along with inhaled corticosteroid by metered dose inhaler with spacer in children between 5-15 years of age with mild acute exacerbation of asthma had similar bronchodilatory effects.. ClinicalTrials.gov: NCT00900874.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Inhalation Spacers; Male; Spirometry; Treatment Outcome

Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.. This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period.. Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC.. Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Budesonide; Drug Substitution; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Failure; Young Adult

Inhaled combined therapy improves the pulmonary function in asthmatic patients. The effect on the airway hyperresponsiveness (AHR) and the efficacy of different pharmacological schedules is not well clarified on adolescent asthmatics.. Evaluate the responses to different combined inhaled therapies in adolescent asthmatics and study its impact on exercise induced AHR.. Basal lung function tests (LFT) were performed in 30 adolescents (13 to 16 years old; 19 female) with allergic asthma. They were submitted to exercise challenge test (EC) followed by bronchodilator test (BD). During 4 weeks, 15 adolescents were submitted to inhaled fluticasone/salmeterol (group A) and other 15 to inhaled budesonide/formoterol (group B). After this period, they underwent another functional evaluation as previous.. Before treatment, pulmonary function was similar in both groups. After 4 weeks of treatment, these groups showed an improvement of the basal LFT (p = 0.001 for FEV1 in both), decrease on bronchoconstriction induced by exercise (NS for both) and less recovery on BD response (p = 0.001 and 0.002, for FEV1 respectively groups A and B). Group B showed a better performance, with higher improvement of basal FEF 25/75 (p = 0.001), reduced bronchoconstriction response to EC (p = 0.008 for FEV1) and fewer response to BD test (p < 0.0001 for FEV1 and 0.024 for FEF 25/75) No adverse events were observed.. After 4 weeks of inhaled combined therapy, these patients improved their pulmonary function and bronchomotricity. Those under budesonide/formoterol showed the highest improvement. These medications are a safe measure in controlling the asthma in these patients.

Topics: Adolescent; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Respiratory Function Tests

Information surrounding the long-term safety of combination inhaled corticosteroid/long-acting β(2)-adrenergic agonist medications in African American asthmatic patients is limited.. We sought to assess safety and asthma control with a budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide over 1 year in African American patients.. This 52-week, randomized, double-blind, parallel-group, multicenter, phase 3B safety study (NCT00419952) was conducted in 742 self-reported African American patients 12 years or older with moderate-to-severe asthma previously receiving medium- to high-dose inhaled corticosteroids. After 2 weeks using a 320 μg twice-daily budesonide pMDI, patients were randomized 1:1 to 320/9 μg twice-daily budesonide/formoterol pMDI or 320 μg twice-daily budesonide pMDI.. Both treatments were well tolerated. Asthma exacerbation incidence and rate (per patient-treatment year) were lower with budesonide/formoterol versus budesonide (incidence, 7.7% vs 14.0% [P= .006]; rate ratio, 0.615 [P= .002]). Time to first asthma exacerbation was longer (P= .018) with budesonide/formoterol versus budesonide. The most common adverse events, regardless of study drug relationship, were headache (9.5% and 7.7%), nasopharyngitis (6.9% and 8.0%), sinusitis (4.0% and 6.3%), and viral upper respiratory tract infection (5.8% and 4.4%) for budesonide/formoterol and budesonide, respectively. Serious adverse events occurred in 12 and 15 patients, respectively; none were considered drug related. No substantial or unexpected patterns of abnormalities were observed in laboratory, electrocardiographic, or Holter monitoring assessments. Hospitalization caused by asthma exacerbation occurred in 0 and 4 patients in the budesonide/formoterol and budesonide groups, respectively. Pulmonary function and asthma control measures generally favored budesonide/formoterol.. In this population budesonide/formoterol pMDI was well tolerated over 12 months, with a safety profile similar to that of budesonide; the asthma exacerbation rate was reduced by 38.5% versus budesonide.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Black or African American; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Safety; Treatment Outcome; United States

Severe asthma remains a worldwide medical problem. However, this disease has not been adequately explored in the elderly. This study was performed to determine how the addition of montelukast to antiasthmatic therapy improves the control of severe asthma in elderly patients.. Elderly patients (>60 years old) with diagnoses of severe asthma were observed over 24 months of therapy: the first 12 months using inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) and the second 12 months with oral montelukast added in two-thirds of the patients, with the remaining third representing the control group. The primary efficacy endpoint of the study was the percentage of days without asthma symptoms in the first 12 months of treatment compared with the percentage after adding montelukast therapy.. A total of 512 elderly, asthmatic patients were included in the study: seventy-one (13.9%) patients had well-controlled asthma, 211 (41.2%) had partly controlled asthma, and 230 (44.9%) had uncontrolled asthma. During the first year of treatment using ICS and LABA, an increase in the median percentage of days without asthma was observed from 50.1% to 62.1%, as well as a decrease in the percentage of days with short beta-receptor agonist use, from 52.2% to 46.8%. These differences were significantly greater after 12 months, when montelukast was added to the therapy (78.4% and 39.5%, respectively). This improvement was not observed in the control group. After 2 years of observation, the median number of asthma exacerbation incidents per patient decreased from 1.6 per year to 1.2 per year when montelukast was added.. Severe asthma in elderly patients is very poorly treated, with this population exhibiting very low compliance with antiasthmatic therapy. Adding montelukast provides benefits and improved control; however, it does not resolve severe asthma control problems.

Topics: Acetates; Administration, Inhalation; Age Factors; Aged; Aged, 80 and over; Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Chi-Square Distribution; Cyclopropanes; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Spirometry; Sulfides; Surveys and Questionnaires

The combination of an inhaled corticosteroid (ICS), budesonide, and a rapid long-acting β(2)-agonist (LABA), formoterol, in a single inhaler for use as maintenance and reliever therapy (Symbicort Turbuhaler SMART™) effectively achieves a high level of asthma control and reduces exacerbations and asthma-related hospitalizations. The COSMOS study, a multinational, 12-month study (N = 2143), compared budesonide/formoterol maintenance and reliever therapy with salmeterol/fluticasone propionate plus as-needed salbutamol, allowing physicians to modify maintenance doses of both combinations according to routine clinical practice.. The aim of this post hoc sub-group analysis of the COSMOS study is to provide focused data on budesonide/formoterol maintenance and reliever therapy compared with salmeterol/fluticasone propionate plus as-needed salbutamol in patients (aged ≥16 years) enrolled across Asian countries, specifically China, Korea, Taiwan and Thailand.. This sub-analysis of the COSMOS study concerns all 404 randomized patients ≥16 years of age (mean forced expiratory volume in 1 second [FEV(1)] 69.1%) who were recruited from Asian countries. Patients received either budesonide/formoterol (Symbicort Turbuhaler SMART™, n = 198), starting dose 160 mg/4.5 mg two inhalations twice daily (bid) [plus additional as-needed inhalations], or salmeterol/fluticasone propionate (Seretide(®) Diskus(®), n = 206), starting dose 50 mg/250 mg bid (plus salbutamol [Ventolin(®)] as needed). Maintenance doses could be titrated by clinicians after the first 4 weeks (budesonide/formoterol maintenance plus as needed, n = 198; salmeterol/fluticasone propionate plus salbutamol, n = 206). To allow for free adjustment in maintenance doses in both arms, the trial was performed open-label; maintenance doses could be titrated by clinicians after the first 4 weeks. The time to first severe exacerbation (defined as deterioration in asthma resulting in hospitalization/emergency room treatment, oral corticosteroids for ≥3 days or unscheduled visit leading to treatment change) was the primary variable.. The time to first severe exacerbation was prolonged in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate plus salbutamol (log-rank p = 0.024). The risk of a first exacerbation was reduced by 44% (hazard ratio 0.56; 95% confidence interval [CI] 0.32, 0.95; p = 0.033) in patients using the adjusted budesonide/formoterol regimen versus titrated salmeterol/fluticasone propionate. The overall exacerbation rates were 0.16 versus 0.26 events/patient-year, respectively, with a 38% reduction (rate ratio 0.62/patient/year; 95% CI 0.41, 0.94; p = 0.024) in favour of the budesonide/formoterol regimen. Compared with baseline, both regimens provided clinically relevant improvements in asthma control, quality of life and FEV(1); no statistically significant differences between the treatment groups were observed. Mean adjusted (standard deviation) ICS dose (expressed as beclomethasone dose equivalents) during treatment, including as-needed budesonide doses, was 944 (281) and 1034 (394) μg/day, respectively, in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate.. In patients (aged ≥16 years) enrolled from Asian countries as part of the COSMOS study, the budesonide/formoterol maintenance and reliever regimen was associated with a lower future risk of exacerbations versus the physicians' free choice of salmeterol/fluticasone propionate dose plus salbutamol. Single inhaler combination treatment with maintenance plus as-needed budesonide/formoterol was also at least as efficacious as salmeterol/fluticasone propionate dose plus salbutamol in improving current asthma control.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Analysis of Variance; Androstadienes; Asia; Asian People; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Proportional Hazards Models; Time Factors; Treatment Outcome; Young Adult

The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD).. We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time.. Children aged 5 to 12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial, and serial dual-energy x-ray absorptiometry scans of the lumbar spine were performed. Annual BMA rates were defined as follows: [(BMD at 4 years' follow-up - BMD at baseline)/4 years].. BMA was calculated for 780 subjects. In boys baseline vitamin D levels significantly modified the relationship between OCSs and BMA (vitamin D × OCS interaction, P= .023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCSs in vitamin D-insufficient boys only (P< .001). Compared with vitamin D-sufficient boys, vitamin D-insufficient boys exposed to more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative to boys who were OCS unexposed).. Vitamin D levels significantly modified the effect of OCSs on BMA in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma might confer benefits to bone health.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bone Density; Budesonide; Calcifediol; Calcification, Physiologic; Child; Child, Preschool; Female; Humans; Male; Nedocromil; Treatment Outcome; Vitamin D

To evaluate the effect of nebulized budesonide (BUD) in acute moderate to severe exacerbations of asthma in children.. Forty children, 5 to 15 years of age, with acute moderate to severe attacks of asthma, were randomized into BUD group and control group, receiving nebulized 0.5% salbutamol (150 µg/kg) + 0.025% ipratropium bromide (1 ml) + 0.05% budesonide (2 ml) or nebulized 0.5% salbutamol (150 µg/kg) + 0.025% ipratropium bromide (1 ml) + saline (2 ml) at half-hourly intervals for 3 doses respectively. Lung function, respiratory rate (RR), heart rate(HR), oxygen saturation (SaO2) and clinical score (CS) were monitored.. The baseline characteristics of the 2 groups were similar. After 3 doses of nebulization, CS, RR, SaO2, FEV(1) and FEV(1)% were significantly improved in both groups (P < 0.05). The CS in BUD group was significantly lower than that in control group at the end of 2 h after the third dose of nebulization 0 (0) vs 0 (1), Z = 2.522, P = 0.012. There were no significant differences in RR, HR and SaO2 between 2 groups (P > 0.05). The improvement of FEV(1)% in the first hour and the second hour after 3 doses of nebulization was 8.0 (6.8)% and 5.5 (6.5)% in BUD group, and 6.0 (8.5)% and 1.0 (6.5)% in control group, the improvement in BUD group being significantly greater than that in control group (Z = 2.270 and 2.686, P = 0.023 and 0.007 respectively). The improvement of FEV(1) in the second hour after 3 doses of nebulization was significantly greater in BUD group than in control group 0.07 (0.12) L vs 0.01 (0.10) L, Z = 2.455, P = 0.014. The full recovery rate in BUD group at the end of 2 h after completion of nebulization was significantly higher than that in control group (17/20, 85.0% vs 9/18, 50.0%, χ(2) = 5.371, P = 0.024). The proportion of patients who needed to use oral corticosteroids was significantly lower in BUD group than in control group (3/20, 15.0% vs 8/18, 44.4%, χ(2) = 3.993, P = 0.046). The hospitalization rate was 5% (1/20) in BUD group, and 17% (3/18) in control group, but the difference was not statistically significant (P > 0.05).. Nebulized BUD in high dose and at short intervals combined with rapid-acting bronchodilators has an additional bronchodilator response, associated with more rapid and better improvement in clinical symptoms and lung function, indicating that it is preferred in the early management of acute moderate to severe exacerbation of asthma in children.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nebulizers and Vaporizers; Treatment Outcome

Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control.. To assess the effect of vitamin D levels on prebronchodilator FEV(1), bronchodilator response, and responsiveness to methacholine (PC(20), provocative concentration of methacholine producing a 20% decline in FEV(1)) in patients with asthma treated with inhaled corticosteroids.. We measured 25-hydroxyvitamin D levels in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program. We divided subjects into the vitamin D sufficiency (>30 ng/ml), insufficiency (20-30 ng/ml), and deficiency (<20 ng/ml) groups. Covariates included age, treatment, sex, body mass index, race, history of emergency department visits, hospitalizations, and season that vitamin D specimen was drawn. Our main outcome measures were change in prebronchodilator FEV(1), bronchodilator response, and PC(20) from enrollment to 8-12 months.. Of the 1,024 subjects, 663 (65%) were vitamin D sufficient, 260 (25%) were insufficient, and 101 (10%) were deficient. Vitamin D-deficient subjects were more likely to be older, African American, and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects. In the inhaled corticosteroid treatment group, prebronchodilator FEV(1) increased from randomization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group (P = 0.0072), in adjusted models.. In children with asthma treated with inhaled corticosteroids, vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency.

Topics: Administration, Inhalation; Asthma; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Monitoring, Physiologic; Nedocromil; Prospective Studies; Reference Values; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Spirometry; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the period after a single day with high reliever use.. Episodes of high reliever use were quantified and exacerbations occurring post-index day with these episodes were examined post hoc in two double-blind studies comparing the efficacy and safety of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART™, Turbuhaler®) 160/4.5 μg twice daily plus as needed with similar or higher maintenance doses of ICS/LABA plus SABA or formoterol.. Budesonide/formoterol maintenance and reliever therapy significantly reduced the risk of episodes of high reliever use (>6 inhalations/day) vs. all alternative ICS/LABA regimens. With conventional fixed-dose treatment the need for exacerbation treatment within 21 days ranged from 6.0-10.1% of days post-index for all regimens compared with 2.5-3.4% of days with budesonide/formoterol maintenance and reliever therapy.. Budesonide/formoterol maintenance and reliever therapy reduces the incidence of high reliever episodes and the exacerbation burden immediately following these episodes vs. alternative ICS/LABA plus SABA regimens at up to double the maintenance dose of ICS.. These studies do not have registration numbers as they were conducted before clinical trial registration was required.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Disease Progression; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Risk Factors; Severity of Illness Index; Treatment Outcome

Tulobuterol patch (Tulo) is often used for treatment of elder patient with asthma in Japan. However, there is no evidence either ICS plus Tulo or ICS/LABA combination is better for elder patient.. Elder patients with asthma (aged≥ 70, n=17) who had treated with budesonide (BUD) 400 μg/day plus Tulo 2 mg/day, were randomly assigned either to change control medication to budesonide/formoterol combination (BUD/FM) 320/9 μg/day or to keep BUD plus Tulo treatment for 12 weeks.. At week 4 and week 12, the BUD/FM group showed significant increase in lung function (FEV1, %FEV1) and mini AQLQ score compared with the BUD plus Tulo group. The BUD/FM group also showed decrease in Tumor Necrosis Factor-alpha level in exhaled breath condensate at week 12. No adverse event was observed in both groups.. In elder patients with asthma, treatment with BUD/FM does not have any clinical disadvantage and may provide better efficacy in lung function, QOL, and possibly anti-inflammation compared with BUD plus Tulo treatment.

Topics: Aged; Aged, 80 and over; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Quality of Life; Terbutaline; Time Factors; Transdermal Patch; Tumor Necrosis Factor-alpha

Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).. A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.. Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.. In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

Topics: Adolescent; Adult; Aged; Asthma; Budesonide; Double-Blind Method; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged

The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.. We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry.. Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants.. The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.).

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Body Height; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Growth; Humans; Intention to Treat Analysis; Male; Nedocromil

Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma.. To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13-regulated miRNAs.. We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results.. Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids.. Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway epithelial cell differentiation. Clinical trial registered with www.clinicaltrials.gov (NCT 00595153).

Topics: Administration, Inhalation; Adult; Asthma; Bronchi; Budesonide; Cells, Cultured; Dose-Response Relationship, Drug; Epithelial Cells; Female; Glucocorticoids; Humans; Interleukin-13; Male; Microarray Analysis; MicroRNAs; Polymerase Chain Reaction

Vitamin D promotes different toleragenic processes of the immune system; however, its role in allergen specific immunotherapy (SIT) is still undefined.. To determine whether the immunologic and clinical effectiveness of allergen SIT depends on the serum level of 25-hydroxyvitamin D (25[OH]D) and its changes during SIT in asthmatic children.. This is a retrospective secondary analysis of pooled data obtained from our 2 recently published prospective, randomized, placebo-controlled trials on asthmatic children undergoing allergen immunotherapy. Both trials, which assessed the effect of different pharmacologic modulation of SIT effectiveness, were conducted according to the same study protocol. Children from the placebo arms in these trials were treated with immunotherapy only and were included in the present analysis. The study population consisted of 36 children. Data concerning clinical (asthma symptoms score and percent change in minimal daily inhaled corticosteroid dose) and immunologic parameters (including serum level of 25[OH]D) were analyzed in all patients.. Patients with a higher serum level of 25(OH)D experienced more significant reduction in asthma symptoms score and steroid-sparing effect of SIT and had higher transforming growth factor â production and higher Foxp3 induction during SIT. Steroid-sparing effect correlated with 25(OH)D serum level at baseline, after 3 months of SIT, and with the changes in serum level of 25(OH)D during the build-up phase of SIT. Better response to SIT was observed among children with an 25(OH)D serum level higher than 30 ng/mL.. The efficacy of allergen SIT correlates with 25(OH)D serum concentration. It seems that a serum level of 25(OH)D higher than 30 ng/mL facilitates the optimal effect of allergen immunotherapy.

Topics: Asthma; Budesonide; Cells, Cultured; Child; Desensitization, Immunologic; Female; Forkhead Transcription Factors; Humans; Male; Placebos; Prospective Studies; Vitamin D

The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂ agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform(®)). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort(®) Turbohaler(®)).. A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (± 3) day screening, 2-4-week run-in, and 12-week treatment periods. Patients aged ≥ 12 years with moderate to severe persistent asthma for ≥ 6 months before screening and forced expiratory volume in one second (FEV₁) 50-80% predicted and ≥ 15% reversibility following salbutamol inhalation were randomized to fluticasone/formoterol 250/10 μg twice daily (n = 140) or budesonide/formoterol 400/12 μg twice daily (n = 139).. Fluticasone/formoterol was comparable to budesonide/formoterol with respect to the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. The LS mean treatment difference was -0.044 L, with a lower 95% confidence interval (CI) greater than the pre-defined non-inferiority limit of -0.2 L (95% CI: -0.130, 0.043 L; p < 0.001). Non-inferiority was also demonstrated for the secondary endpoints mean change in FEV₁ from baseline (pre-dose) to 2 hours post-dose at Week 12, and discontinuations due to lack of efficacy. Similar results were obtained for both treatment groups for all other secondary endpoints. Fluticasone/formoterol had a good safety profile that was comparable with budesonide/formoterol.. This study demonstrated comparable efficacy of fluticasone/formoterol to budesonide/formoterol in terms of the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. This was supported by comparable results for both treatments for all secondary endpoints.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Young Adult

Topics: Administration, Inhalation; Asthma; Bronchial Provocation Tests; Budesonide; Child; Dry Powder Inhalers; Histamine; Humans; Maximal Voluntary Ventilation; Treatment Outcome

The mechanisms through which rhinitis affects asthma have not been completely elucidated. We explored whether the effect of nasal treatment on asthma control and respiratory-related quality of life (HRQoL) is mediated by inflammatory changes of the upper and lower airways.. Allergic rhinitics with mild asthma were randomized to a 14-day treatment period with either nasal budesonide 100 μg, 1 puff per nostril twice a day, or placebo. Clinical, functional, and biological evaluations were performed before and after treatment.. Twenty subjects (M/F: 10/10; age: 31 ± 15 years; mean ± SD) were enrolled, and a total of 17 individuals completely participated in the study. Lung function was within the normal range. The total asthma control test (ACT) score was 20 ± 5.3 and the RHINASTHMA Global Summary (GS) was 44 ± 15. The percentage proportion of eosinophils in nasal lavage was 9.9% and significantly correlated with spirometric parameters reflecting peripheral airway function (for FEF(50): r = 0.48, p = .03; for FEF(25): r = 0.47, p = .03). The pH of the exhaled breath condensate (EBC) was 7.33 ± 0.4. After nasal treatment, the percentage proportion of eosinophils fell significantly (p = .002), and changes in percentage proportion of eosinophils were associated with changes both in the ACT score (r = 0.76, p = .04) and in the RHINASTHMA GS (r = 0.77, p = .02). The increase in the pH of the EBC was not associated with changes in the ACT score or with the RHINASTHMA GS.. These findings confirm that, in subjects with allergic rhinitis with mild asthma, nasal inflammation impacts on asthma control and HRQoL. The improved control of respiratory symptoms obtained with nasal corticosteroids seems to be mediated by functional changes in the peripheral airways.

Topics: Administration, Intranasal; Adult; Asthma; Budesonide; Eosinophils; Female; Glucocorticoids; Humans; Male; Maximal Midexpiratory Flow Rate; Nasal Cavity; Nasal Lavage; Quality of Life; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Surveys and Questionnaires; Vital Capacity

To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence, that is correct use of the inhaler.. In an 18-month study, children aged 5-10 years with asthma received twice daily budesonide via a TBH. Parents and children were trained in the correct use of the inhaler before the study started. For each inhalation, peak inspiratory flow through the TBH (PIF(TBH)) was recorded with an electronic pneumotachograph. The PIF(TBH) recordings were used to calculate true adherence for the first and last 45-day periods in the study by multiplying adherence in using the device (percentage of days with PIF(TBH) recordings) with inhaler competence (correct use of inhaler defined as PIF(TBH) values >40 l/min).. True adherence, adherence, inhaler competence and PIF(TBH).. 115 children were treated. The mean (morning and evening) true adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true adherence was due to the decline in adherence. The largest decline in true adherence occurred in older children.. True adherence with budesonide TBH treatment decreased significantly during the 18-month study due to a decrease in adherence. Inhaler competence with the correct use of the budesonide TBH was high and unchanged over the study period.

Topics: Administration, Inhalation; Age Factors; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Dry Powder Inhalers; Equipment Design; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Peak Expiratory Flow Rate; Self Administration; Self Efficacy

Once the optimal dose is reached, subcutaneous immunotherapy [SCIT] with mite extract is capable of reducing symptoms and the need for rescue medication.. To assess the capacity of a subcutaneous extract of mites [D. pteronyssinus] to bring about a reduction in concomitant medication as well as in vivo and in vitro changes in just 2-3 months of treatment in patients with allergic asthma.. A total of 45 patients with persistent mild-moderate allergic asthma due to sensitisation to D. pteronyssinus were included in a multi-centre, double-blind, placebo-controlled trial. Length of treatment was 4 months. After a period for adjusting medication in order to classify asthma severity appropriately, patients were commenced on treatment of 400 or 800 g/day of budesonide as concomitant medication.. After 4 months of treatment there were no significant changes in the budesonide dose between the active group and the placebo group. In the active group there was a significant difference between active and placebo group in sIgG4 [p=.0003], as well as a significant increase in the cutaneous tolerance index [2.81, CI 95%: 1.29 - 7.48, which was significant with a Confidence Interval of 95%]. These changes were not observed in the placebo group.. After just 4 months of treatment, SCIT was capable of inducing in vivo and in vitro changes, but these changes were not reflected in improved clinical outcome within the first 4 months of therapy.

Topics: Adolescent; Adult; Allergens; Animals; Anti-Allergic Agents; Antigens, Dermatophagoides; Asthma; Budesonide; Dermatophagoides pteronyssinus; Desensitization, Immunologic; Double-Blind Method; Female; Humans; Immunoglobulin G; Male; Reproducibility of Results; Severity of Illness Index; Skin Tests; Tissue Extracts; Young Adult

The adverse effect of inhaled corticosteroids (ICS) treatment on bone metabolism in children with asthma is still controversial, and a possible beneficial effect of vitamin D added to ICS on bone turnover is uncertain.. We conducted a randomized, double-blind, parallel-group, 6-month trial to assess the effects of a medium and high dose of ICS and a high-dose ICS with vitamin D on bone metabolism in children with newly diagnosed atopic asthma.. 96 children were equally randomized to 4 groups receiving the following doses of inhaled budesonide [μg/day]: 400 (ICS 400 group), 800 (ICS 800 group), 800 with oral vitamin D (ICS 800 with vit D group), and montelukast as a control (control group). Markers of bone production (osteocalcin, alkaline phosphatase) and bone degradation (amino-terminal cross-linked telopeptide of type I collagen--NTx, carboxy-terminal telopeptides of type I collage), and also concentration of 25-hydroxycholecalciferol (25OH D) and calcium-phosphorus balance (calcium, phosphorus, parathormon-PTH) in serum and/or urine were assessed twice: before and after 6 months of treatment.. We obtained a significant decrease in phosphorus and PTH serum levels in ICS 400 and ICS 800 with vit D groups compared to control group, and a significant decrease of NTx urine level in ICS 800 with vit D group.. Medium doses of inhaled corticosteroids exert an advantageous effect on bone metabolism in newly diagnosed asthmatic children. Vitamin D together with a high dose of inhaled corticosteroids has a beneficial effect on both calcium-phosphorus balance and collagen turnover.

Topics: Acetates; Administration, Inhalation; Adolescent; Asthma; Bone and Bones; Budesonide; Child; Child, Preschool; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Parathyroid Hormone; Phosphorus; Quinolines; Sulfides

Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms. No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children. The goal of our study was (1) to assess the association of asthma symptoms with severe asthma exacerbations and (2) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations.. The Childhood Asthma Management Program was a multicenter clinical trial of 1,041 children randomized to receive budesonide, nedocromil, or placebo (as-needed β-agonist). We conducted a post hoc analysis of diary cards that were completed by subjects on a daily basis to categorize subjects as having persistent vs intermittent symptoms. We defined a severe asthma exacerbation as an episode requiring ≥ 3 days use of oral corticosteroids, hospitalization, or ED visit due to asthma based on self-report at study visits every 4 months.. While accounting for longitudinal measures, having persistent symptoms from asthma was significantly associated with having severe asthma exacerbations. Predictors of having persistent symptoms compared with intermittent symptoms included not being treated with inhaled corticosteroids, lower FEV(1)/FVC ratio, and a lower natural logarithm of provocative concentration of methacholine producing a 20% decline in FEV(1) (lnPC(20)). Predictors of having one or more severe asthma exacerbations included younger age, history of hospitalization or ED visit in the prior year, ≥ 3 days use of oral corticosteroids in the prior 3 months, lower FEV(1)/FVC ratio, lower lnPC(20), and higher logarithm to the base 10 eosinophil count; treatment with inhaled corticosteroids was predictive of having no severe asthma exacerbations.. Patients with persistent symptoms from asthma were more likely to experience severe asthma exacerbations. Nevertheless, demographic and laboratory predictors of having persistent symptoms are different from predictors of severe asthma exacerbations. Although symptoms and exacerbations are closely related, their predictors are different. The current focus of the National Asthma Education and Prevention Program guidelines on the two separate domains of asthma control, impairment and risk, are supported by our analysis.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Nedocromil; Prognosis; Recurrence; Severity of Illness Index; Time Factors

Topics: Acute Disease; Adolescent; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Respiratory Function Tests; Respiratory Tract Infections; Treatment Outcome; Vitamin D

A hydrofluoroalkane formulation of budesonide pressurized metered-dose inhaler has been developed to replace the existing chlorofluorocarbon one. The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations.. Systemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler formulations at 800 µg twice daily was determined during a randomized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers. Measurements included the following: plasma cortisol AUC(24h) [area under the concentration-time curve (0-24 h)], budesonide AUC(0-12h) and C(max) . Clinical efficacy was determined during a randomized crossover pharmacodynamic study in asthmatic patients receiving 200 µg followed by 800 µg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered-dose inhaler each for 4 weeks. Methacholine PC(20) (primary outcome), exhaled nitric oxide, spirometry, peak expiratory flow and symptoms were evaluated.. In the pharmacokinetic study, there were no differences in cortisol, AUC(0-12h) [area under the concentration-time curve (0-12 h)], T(max) (time to maximum concentration) or C(max) (peak serum concentration) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered-dose inhaler. The ratio of budesonide hydrofluoroalkane vs. chlorofluorocarbon pressurized metered-dose inhaler for cortisol AUC(24h) was 1.02 (95% confidence interval 0.93-1.11) and budesonide AUC(0-12h) was 1.03 (90% confidence interval 0.9-1.18). In the asthma pharmacodynamic study, there was a significant dose response (P < 0.0001) for methacholine PC(20) (provocative concentration of methacholine needed to produce a 20% fall in FEV(1) ) with a relative potency ratio of 1.10 (95% confidence interval 0.49-2.66), and no difference at either dose. No significant differences between formulations were seen with the secondary outcome variables.. Hydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Asthma; Bronchodilator Agents; Budesonide; Chlorofluorocarbons; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Respiratory Function Tests; Therapeutic Equivalency; Treatment Outcome

Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting β(2)-agonists (LABA), and with as-needed short-acting β(2)-agonists (SABA) or LABA. Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6-12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model. The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36% versus pooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52% versus the same maintenance dose of ICS/LABA (RR 0.48; p<0.001); there were nonsignificant reductions versus higher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbations versus as-needed SABA (RR 0.96). Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Asthma; Budesonide; Child; Child, Preschool; Common Cold; Double-Blind Method; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Poisson Distribution; Respiratory Tract Infections; Retrospective Studies; Risk; Time Factors

A randomised 6-month study compared two maintenance doses of budesonide/formoterol (Symbicort® Turbuhaler® (h) maintenance and reliever therapy (Symbicort SMART®), 160/4.5 μg 1 × 2 and 2 × 2, in 8053 asthmatics with symptoms despite treatment with inhaled corticosteroids ± inhaled long-acting β2-agonists. This analysis compared response to the two treatments in elderly patients, ≥ 65 years, with that in younger patients. Elderly patients with early- or late-onset asthma were also compared. Elderly patients had lower post-bronchodilator FEV1 percentage predicted normal at baseline than younger patients (85.6% vs. 91.0%, respectively). The elderly had more exacerbations and risk of first severe exacerbation was increased by 55.3% (hazard ratio 1.553; 95% confidence interval: 1.249-1.931, p < 0.0001). However, no differences in exacerbations were seen between 1 × 2 or 2 × 2 budesonide/formoterol maintenance and reliever therapy treatment in the elderly. Five-item Asthma Control Questionnaire (ACQ-5) scores improved equally in the two age groups. Changes in mean ACQ-5 scores between 1 × 2 and 2 × 2 were significant in both age groups but not clinically relevant (≥ 65 years, 0.12; p = 0.018; <65 years, 0.09; p < 0.0001). Elderly patients with early- and late-onset asthma responded equally well to treatment. Budesonide/formoterol maintenance and reliever therapy (1 × 2 or 2 × 2) is an effective, well-tolerated and practical treatment concept in elderly and younger asthmatic patients.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Disease Progression; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Inhaled combination therapy composing of long-acting β2-agonist and corticosteroid has been widely applied in the management of asthma, but observed treatment responses vary. The aim of this study was to evaluate the pharmacogenetic effect of the adenylyl cyclase type 9 (ADCY9) gene polymorphism on combination therapy.. Eighty-six mild to moderate Korean asthmatics were enrolled in this clinical trial. After the 2-week 'run-in' period, patients received budesonide (an inhaled corticosteroid) and formoterol (long-acting β2-agonist) during the following 12-week active treatment period. Forced expiratory volume in 1 s (FEV(1) ) and maximum mid-expiratory flow (MMEF) levels were measured at all visits as primary outcome. ADCY9 (Ile772Met, 150127 C/T, 150130 C/T, 150397 C/T, 150479 C/T, TTTA (5/4) ) and β2-adrenergic receptor (ADRB2, Arg16Gly) gene polymorphisms were genotyped.. Significant associations were observed between the ADCY9 single nucleotide polymorphisms and percent changes in FEV(1) (Ile772Met T/C, P = 0·030) and MMEF (150397 C/T, P = 0·016) after 8 weeks of combination therapy. Haplotype associations were also observed with respect to percent changes in FEV(1) after 8 weeks of therapy (Ht3[TTCC], P = 0·017). Additive therapeutic effect was observed in those with the ADCY9 Ile772Met and ADRB2 Arg16Gly gene polymorphisms in terms of percent change in FEV(1) after 8 and 12 weeks of therapy (P = 0·002 and P = 0·027 respectively).. Our results suggest that ADCY9 gene polymorphisms may alone, and in combination with ADRB2 gene polymorphisms, contribute to individual response to combination therapy in mild to moderate asthmatics.

Topics: Adenylyl Cyclases; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Genetic Association Studies; Glucocorticoids; Humans; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Republic of Korea; Respiratory System; Retrospective Studies; Severity of Illness Index

Baseline inhaled corticosteroid (ICS) dose may be a factor for prescribers to consider when they select a budesonide/formoterol maintenance and reliever therapy regimen for symptomatic asthmatics.. A 6-month randomized study compared two maintenance doses of budesonide/formoterol 160/4.5 µg, 1 × 2 and 2 × 2, plus as needed, in 8424 asthma patients with symptoms when treated with ICS ± an inhaled long-acting β(2)-agonist (LABA). In the total study population, 1339 (17%) were high-dose ICS (HD) users (≥ 1600 µg/day budesonide). This HD stratum was compared with the rest of the study population, divided into low-dose (LD; 400 µg/day) and medium-dose strata (MD; 401-1599 µg/day) with regard to severe asthma exacerbations and mean changes in five-item Asthma Control Questionnaire (ACQ(5)) scores from baseline.. In all three strata there were fewer exacerbations in the 2 × 2 treatment groups (yearly rates 0.268, 0.172 and 0.094) than in the 1 × 2 treatment groups (yearly rates 0.232, 0.138 and 0.764). In no stratum was the difference between the treatment groups statistically significant. There was no statistically significant difference in time to the first severe exacerbation between the treatments 2 × 2 and 1 × 2 in the HD group (hazard ratio 0.944, p = 0.75). The adjusted mean changes in ACQ(5) scores in the HD, MD and LD strata were -0.89, -0.61 and -0.65, respectively, with 1 × 2 treatment and -0.90, -0.74 and -0.76, respectively, with 2 × 2 treatment. In the MD and LD strata, the difference between doses was significant in favour of 2 × 2 (MD p < 0.0001; LD p = 0.004), but not in the HD stratum (p = 0.870). No difference in serious adverse events was seen.. Compared with the LD and MD strata, the HD stratum patients had more exacerbations and a shorter time to first exacerbation. However, there were no differences in response between the 1 × 2 and 2 × 2 groups in any of the strata. This indicates that patients using budesonide/formoterol maintenance and reliever therapy, irrespective of baseline ICS dose, can be switched to 1 × 2 with its lower steroid load. ACQ(5) scores improved more in the HD stratum than in the MD and LD strata indicating, among other things, that HD patients were not overtreated at baseline.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Female; Humans; Male; Middle Aged; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

A course of combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2) agonist (LABA) for asthma can improve lung function, asthma symptoms and reduce exacerbations. Because both medicinal substance and inhalation devices are associated with clinical efficacy, each ICS/LABA combination may have different features. This study aimed to compare the effects of two widely available formulations, budesonide/formoterol (BUD/FM) delivered by a Turbuhaler(®), and fluticasone/salmeterol (FP/SM) delivered by a Diskus(®), on small airway function and airway inflammation.. Asthmatic patients (n = 40) treated twice daily with FP/SM 250/50 μg with forced expiratory volume in 1 s values controlled above 80% of the predicted normal but with suspected persistent airway inflammation and small airway impairment were enrolled in the study. Patients were randomized into two groups, receiving either twice daily BUD/FM 320/9 μg or FP/SM 250/50 μg, and treatment efficacy was compared after 4 weeks. Outcomes included impulse oscillometry (IOS), fractional exhaled nitric oxide (FeNO), spirometry and Asthma Control Questionnaire (ACQ) scores.. Patients in the BUD/FM group showed significant improvements in their IOS and spirometry parameters of small airway function, FeNO values and ACQ scores, compared with the FP/SM group. There were good correlations between IOS parameters, FeNO and ACQ score changes over the course of the treatment.. BUD/FM twice daily significantly improved small airway impairment and airway inflammation in asthmatic patients, leading to a reduction in asthma symptoms and achievement of good asthma control. In addition, improvement of small airway function may improve airway inflammation and/or lead to better controlled asthma.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Oscillometry; Spirometry

The purpose of this study was to compare the efficacy of budesonide/formoterol maintenance and reliever therapy (Symbicort® SMART®, AstraZeneca AB, Södertälje, Sweden) with conventional best standard treatment (CBST) in patients with persistent asthma in an attempted 'real life' setting.. In total, 1835 patients from Denmark, Finland and Norway were randomized to 26 weeks treatment with budesonide/formoterol 160/4,5 µg twice daily plus budesonide/formoterol 160/4,5 µg for symptom relief or CBST according to the Global Initiative for Asthma guidelines. The study was randomized, open-label and designed to reflect 'real life' asthma management. Efficacy variables were time to first severe asthma exacerbation, rate of severe asthma exacerbations, asthma control (Asthma Control Questionnaire-5) and use of inhaled glucocorticosteroids (IGCS).. Treatment with budesonide/formoterol maintenance and reliever therapy led to a 21% reduction in time to first severe asthma exacerbation compared with CBST, although not statistically significant (hazard ratio 0.794, P = 0.189). A trend towards a reduction in the rate of severe exacerbations in the budesonide/formoterol maintenance and reliever therapy group was observed (16 vs 22 events/100 patient years; P = 0.058). The percentage of patients with well-controlled asthma increased significantly among those treated with budesonide/formoterol maintenance and reliever therapy compared with CBST (45% vs 40%; odds ratio 1.39; P < 0.01), in spite of a significant 31% reduction in total mean daily IGCS dose (P < 0.0001). No difference in mean as-needed medication use was seen (P = 0.98). All treatments were well tolerated.. Budesonide/formoterol maintenance and reliever therapy resulted in a better overall asthma control with a significant lower daily IGCS dose compared with CBST.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Administration Schedule; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Lung; Male; Middle Aged; Research Design; Severity of Illness Index; Treatment Outcome; Young Adult

The goal was to determine if adding inhaled budesonide to standard asthma therapy improves outcomes of pediatric patients presenting to the emergency department (ED) with acute asthma.. The authors conducted a randomized, double-blind, placebo-controlled trial in a tertiary care, urban pediatric ED. Patients 2 to 18 years of age with moderate to severe acute asthma were randomized to receive either a single 2-mg dose of budesonide inhalation suspension (BUD) or normal sterile saline (NSS) placebo, added to albuterol, ipratropium bromide (IB), and systemic corticosteroids (SCS). The primary outcome was the difference in median asthma scores between treatment groups at 2 hours. Secondary outcomes included differences in vital signs and hospitalization rates.. A total of 180 patients were enrolled. Treatment groups had similar baseline demographics, asthma scores, and vital signs. A total of 169 patients (88 BUD, 81 NSS) were assessed for the primary outcome. No significant difference was found between groups in the change in median asthma score at 2 hours (BUD -3, NSS -3, p = 0.64). Vital signs at 2 hours were also similar between groups. Fifty-six children (62%) were admitted to the hospital in the BUD group and 55 (62%) in the NSS group (difference 0%, 95% confidence interval [CI] = -14% to 14%). Neither multivariate adjustment nor planned subgroup analysis by inhaled corticosteroids (ICS) use prior to the ED significantly altered the results.. For children 2 to 18 years of age treated in the ED for acute asthma, a single 2-mg dose of budesonide added to standard therapy did not improve asthma severity scores or other short-term ED-based outcomes.

Topics: Administration, Inhalation; Adolescent; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Ipratropium; Male; Severity of Illness Index; Treatment Outcome; Young Adult

Few clinical trials in asthma have focused on Hispanic populations.. To compare the efficacy and safety of budesonide/formoterol (BUD/FM) with BUD in an ethnically diverse group of Hispanic participants with asthma previously treated with inhaled corticosteroids (ICS).. This 12-week, randomized, double-blind, active-controlled study (NCT00419757) was designed to enroll Hispanic participants (self-reported) (≥12 years of age) with moderate to severe asthma requiring medium- to high-dose ICS. After a 2-week run-in period (low-dose BUD pressurized metered-dose inhaler [pMDI] 80 μg × 2 inhalations [160 μg] twice daily), participants with a symptom score greater than 0 (scale: 0-3) on 3 or more of 7 run-in days and forced expiratory volume in 1 second (FEV(1)) 45%-85% predicted were randomized to BUD/FM pMDI 160/4.5 μg × 2 inhalations (320/9 μg) twice daily or BUD pMDI 160 μg × 2 inhalations (320 μg) twice daily.. Randomized participants (n = 127 BUD/FM; n = 123 BUD) were predominately Mexican (51%) or Puerto Rican (21%). During low-dose ICS run-in, the mean symptom score was 1.0; however, mean predose FEV(1) improved (2.10-2.21 L). During randomized treatment, small, but not statistically significant, improvements favored BUD/FM vs BUD (am peak expiratory flow [PEF; primary efficacy variable] 25.4 vs 19.9 L/min; pm PEF 20.6 vs 15.8 L/min; predose FEV(1) 0.16 vs 0.11 L; rescue medication use -0.7 vs -0.6 inhalations/d). Most adverse events were mild or moderate in intensity.. Improvement in clinically relevant control end points occurred in both BUD/FM and BUD groups; both treatments were well tolerated in this Hispanic asthma population but were not significantly differentiated.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Hispanic or Latino; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome; Young Adult

Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 ug b.i.d.) or montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP), and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP.. a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.

Topics: Acetates; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Cell Count; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Humans; Male; Neutrophils; Quinolines; Severity of Illness Index; Single-Blind Method; Sputum; Sulfides; Uteroglobin; Young Adult

Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophages.. In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR.. GR-GRE binding was significantly increased after treatment with SYM100 (3.5 OD/10 μg protein, median, p < 0.05) versus placebo (1.3) and BUD200 (1.6), and the induction was higher than that of BUD800 (2.4). MKP-1 mRNA was increased and IL-8 mRNA was significantly inhibited by BUD800, SYM100 and SYM200 versus placebo.. The effects of SYM100 and SYM200 on GR activation were not different from that of BUD800 and superior to BUD200. Thus, it has been confirmed at a molecular level that inhaled combination therapy with a lower dose of budesonide has an equivalent effect to a high dose of budesonide alone. In addition, GR-GRE binding is found to be a valuable pharmacodynamic marker for steroid efficacy in clinical studies.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Dual Specificity Phosphatase 1; Enzyme-Linked Immunosorbent Assay; Ethanolamines; Female; Glucocorticoids; Humans; Interleukin-8; Male; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Sputum

Asthma exacerbations during pregnancy are common and can be associated with substantial maternal and fetal morbidity. Treatment decisions based on sputum eosinophil counts reduce exacerbations in non-pregnant women with asthma, but results with the fraction of exhaled nitric oxide (F(E)NO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on F(E)NO and symptoms would reduce asthma exacerbations.. We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks' gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or F(E)NO concentrations (active intervention group) used to uptitrate (F(E)NO >29 ppb) or downtitrate (F(E)NO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting β2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when F(E)NO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482.. 111 women were randomly assigned to the F(E)NO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the F(E)NO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325-0·755; p=0·001). The number needed to treat was 6. In the F(E)NO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2-59·3] in F(E)NO group vs 54·2 [46·1-57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046).. Asthma exacerbations during pregnancy can be significantly reduced with a validated F(E)NO-based treatment algorithm.. National Health and Medical Research Council of Australia.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Double-Blind Method; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Nitric Oxide; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Vital Capacity

To study the effectiveness and safety in a real-life setting of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy® (Symbicort SMART®), a simplified management approach with one inhaler, compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma.. Open-label randomized controlled parallel-group trial, 6-month treatment.. A total of 654 adult patients, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting β(2)-agonist.. Time to first severe asthma exacerbation and number of severe asthma exacerbations.. No difference between groups was seen in time to first severe exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations, and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group (including as-needed use) versus the CBP group (799 μg vs.1184 μg; p < .001). Mean scores in Asthma Control Questionnaire, five-question version, improved significantly in the SMART group compared with the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated. The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP (€295.32 vs. €387.98, p < .0001).. A simplified regimen using budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Respiratory Function Tests; Spain; Surveys and Questionnaires; Young Adult

Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.. We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.. The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.. A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).

Topics: Administration, Inhalation; Administration, Oral; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Drug Administration Schedule; Female; Glucocorticoids; Humans; Infant; Male; Prednisolone; Respiratory Sounds; Severity of Illness Index; Treatment Failure

Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma. However, there are no randomized data available to elucidate the relation between inhaled corticosteroid suppressed short-term lower leg and height growth. The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 μg once daily in the morning or montelukast 5 mg once daily. A total of 52 pre-pubertal children with asthma were included in a randomized open-label parallel group study. Length of the lower leg and height were measured by knemometry and stadiometry, respectively, at study entry and after 2, 4, 12, 20, 28, 36, 44 and 52 wks. Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group (p < 0.0001). Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children (p = 0.02). Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [95% CI: (0.20; 1.79)]. There was a strong linear correlation between lower leg and height growth in both groups, rho = 0.96 (budesonide) and 0.98 (montelukast). In conclusion, 1-yr height growth suppression of budesonide 200 μg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids. Short-term knemometry should be performed as part of the safety assessments of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated.

Topics: Administration, Inhalation; Asthma; Body Height; Budesonide; Child; Child, Preschool; Dry Powder Inhalers; Female; Follow-Up Studies; Humans; Leg Bones; Male

The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo.. We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide.. At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms.. Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Lung; Macrophages; Male; Matrix Metalloproteinase 8; Respiratory Function Tests; Sputum; Tissue Inhibitor of Metalloproteinase-1

In adults, asthma treatment with high doses of inhaled corticosteroids has resulted in dermal thinning. The aim of this study was to investigate the skin thickness in children with asthma during budesonide treatment. In a double-blind study, 113 children, 5-10 y old, with persistent asthma received budesonide 400 microg twice daily for 1 mo and thereafter 200 microg twice daily for 5 mo. Thereafter, 56 children received 100 microg twice daily for 1 y, whereas 57 other children used budesonide periodically for exacerbations. An additional 54 children were treated with disodium cromoglycate (DSCG) for 18 mo. Skin thickness was measured on each forearm before and after treatment for 6, 12, and 18 mo using a 20-MHz high-resolution ultrasonic device. The initial 6-mo budesonide treatment resulted in a greater reduction in mean skin thickness in the forearms compared with DSCG (right: -35.9 versus -5.9 microm; p = 0.004; left: -30.6 versus -7.3 microm; p = 0.03). At month 18, the inter-group differences were no longer significant. Budesonide inhalations in daily doses of 400-800 microg in prepubertal children with newly detected asthma may cause minor dermal thinning. The changes were reversible during low dose or periodic treatment with budesonide.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Atrophy; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Finland; Forearm; Humans; Male; Severity of Illness Index; Skin; Skinfold Thickness; Time Factors; Treatment Outcome; Ultrasonography

Combining inhaled corticosteroids with long-acting beta(2)-agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma.. We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling.. Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment.. Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area.. The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.

Topics: Actins; Administration, Inhalation; Adult; Airway Remodeling; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Eosinophilia; Ethanolamines; Female; Formoterol Fumarate; Humans; Inflammation; Male; Microscopy, Electron, Transmission; Muscle, Smooth; Sputum

There are various ways to classify asthma control; however, no classification is universally accepted. This retrospective analysis compared asthma control as assessed by the Asthma Control Questionnaire (5-item version; ACQ-5), Global Initiative for Asthma (GINA) or Gaining Optimal Asthma Control (GOAL) study criteria. Pooled data at the final study week (n = 8,188) from three budesonide/formoterol maintenance and reliever therapy studies which measured ACQ-5 were stratified according to GINA or GOAL criteria and ACQ-5 score distribution. The percentages of patients with a controlled/partly controlled week (GINA), totally/well-controlled week (GOAL) and range of ACQ-5 cut-off points were compared. Patients with GINA controlled, partly controlled and uncontrolled asthma had mean ACQ-5 scores of 0.43, 0.75 and 1.62, respectively. Patients with GOAL totally controlled, well-controlled and uncontrolled asthma had ACQ-5 scores of 0.39, 0.78 and 1.63. The kappa measure of agreement was 0.80 for GINA and GOAL criteria, and 0.63 for GINA controlled/partly controlled and ACQ-5 <1.00. ACQ-5 detected clinically important improvements in 49% of patients who, according to GINA criteria, remained uncontrolled at the end of the study. Asthma control measured by GINA or GOAL criteria provides similar results. GINA Controlled/Partly Controlled and GOAL Totally Controlled/Well-Controlled correspond to ACQ-5 <1.00. The ACQ-5 is more responsive to change in a clinical trial setting than a categorical scale.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Asthma; Budesonide; Child; Double-Blind Method; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Medicine; Retrospective Studies; Surveys and Questionnaires; Time Factors

The course of mild to moderate persistent asthma in children is not clearly established.. To determine the rate and predictors for remitting, periodic, and persistent asthma in adolescence.. The Childhood Asthma Management Program (CAMP) was a 4.3-year randomized, double-masked, multicenter trial in children with mild to moderate persistent asthma that compared continuous therapy with either budesonide or nedocromil, each to placebo, followed by a 4-year observational follow-up period. Asthma activity during the observation period included remitting (no asthma activity in the last year), persistent (asthma activity in every quarter), and periodic asthma (neither remitting nor persistent).. Asthma was identified as remitting in 6%, periodic in 39%, and persistent in 55% of the 909 participants, with no effect noted from earlier anti-inflammatory treatment during the CAMP trial. Within all 3 asthma activity categories, improvements in airway hyperresponsiveness, eosinophilia, and asthma morbidity were observed over time. Features at entry into CAMP associated with remitting versus persistent asthma were lack of allergen sensitization and exposure to indoor allergens (odds ratio [OR], 3.23; P < .001), milder asthma (OR, 2.01; P = .03), older age (OR, 1.23; P = .01), less airway hyperresponsiveness (higher log methacholine FEV(1) PC(20) (OR, 1.39; P = .03), higher prebronchodilator FEV(1) percent predicted (OR, 1.05; P = .02), and lower forced vital capacity percent predicted (OR, 0.96; P = .04).. Remission of asthma in adolescence is infrequent and not affected by 4 years of anti-inflammatory controller therapy. Factors such as sensitization and exposure, low lung function, and airway greater hyperresponsiveness decrease the likelihood of remitting asthma.

Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nedocromil; Respiratory Function Tests; Treatment Outcome

Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler with fixed-dose fluticasone propionate/salmeterol dry powder inhaler regimens on patient-reported outcomes in patients aged > or =18 years with moderate to severe asthma.. In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 microg x 2 inhalations (320/9 mug) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 microg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 microg twice daily to 320/9 microg once daily or 640/18 microg twice daily).. Mean improvements from baseline to end of treatment in the Asthma Quality of Life Questionnaire (standardized) overall and individual domain scores and the Asthma Control Questionnaire score were clinically important (> or =0.5 points) for all treatments. Patients in both budesonide/formoterol groups reported greater treatment satisfaction on the Asthma Treatment Satisfaction Measure questionnaire than patients in the fluticasone propionate/salmeterol dry powder inhaler group for the attributes of timely relief of symptoms (p < or = .037) and feel medication working (p < or = .020). Onset of Effect Questionnaire scores showed a greater percentage of patients perceiving onset of effect with budesonide/formoterol regimens versus fixed-dose fluticasone propionate/salmeterol (p < or = .002).. Treatment regimens did not differ regarding improvements in asthma-specific quality of life and asthma control. Questions related to perceived rate of onset and feeling medication working in the Asthma Treatment Satisfaction Measure and Onset of Effect Questionnaire generally elicited somewhat more favorable responses with budesonide/formoterol pressurized metered-dose inhaler regimens versus fixed-dose fluticasone propionate/salmeterol dry powder inhaler.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

There is a lack of evidence for treatment of newly diagnosed asthma, and they are based mainly on expert opinion. This pilot study was aimed at evaluating the effects of inhaled corticosteroid (ICS) in two different doses and montelukast sodium on clinical symptoms and lung function in children with newly diagnosed asthma. This was a randomized, double-blind, parallel-group, 12-month pilot trial, studying the effects of budesonide 800 mcg/day and 400 mcg/day and montelukast 5 or 10 mg tablet according to age on clinical symptoms and lung function in 60 children with newly diagnosed asthma. After 6 months of treatment with different doses of inhaled budesonide and montelukast sodium, asthma control and lung function significantly improved in all three groups of treatment; there were no differences between groups. We found significant correlation between time of enrollment and individual answer to the treatment in montelukast group only; children enrolled later (at the end of heating season) responded better to treatment. The answer to both ICS doses was independent from time of enrollment. The results of the present pilot study suggest that natural exposure, even to perennial allergens, should be considered in choosing the initial asthma treatment. We showed that montelukast may be used as initial asthma therapy in children allergic to house-dust mites preferably at the end of the heating season. Therefore, ICS could be a better choice as initial asthma therapy during maximum allergen exposure.

Topics: Acetates; Administration, Inhalation; Adolescent; Animals; Antigens, Dermatophagoides; Asthma; Budesonide; Child; Child, Preschool; Cyclopropanes; Evidence-Based Medicine; Female; Humans; Male; Pilot Projects; Pyroglyphidae; Quinolines; Respiratory Function Tests; Sulfides

Cytokines and chemokines play important roles in asthma. However, little information exists on the effects of inhaled corticosteroids on cytokine and chemokine plasma levels in childhood asthma. We compared the pharmaceutical effects of two inhaled corticosteroids used in pediatric patients with mild-to-moderate asthma, budesonide and fluticasone propionate.. Pediatric patients aged 5-18 years old were enrolled in this randomized, open-label, observer-blinded study and received 3 months of treatment with either inhaled budesonide (200 microg/puff) or fluticasone propionate (250 microg/puff), at two puffs per day. Peak expiratory flow (PEF), exhaled nitric oxide, Asthma Control Test (ACT), plasma Levels of tumor necrosis factor-alpha, thymus and activation-regulated chemokine, and interferon-inducible protein 10 were measured before treatment and monthly for 3 months after treatment.. There were six patients in the budesonide group, and eight in the fluticasone group. After 3 months, both groups showed improved PEF. In the first month, PEF improved more in the budesonide group than in the fluticasone group, though the difference was not significant. After treatment, ACT scores in both groups were well controlled, except for one patient in the fluticasone group. The fluticasone group had a more significant reduction in exhaled nitric oxide than the budesonide group in the first month.. Improvements in lung function were more rapid in the budesonide group than the fluticasone group. However, patients in the fluticasone group had better anti-inflammatory responses than those in the budesonide group. We conclude that each inhaled corticosteroids have its own clinical and laboratory effects.

Topics: Adolescent; Androstadienes; Asthma; Breath Tests; Budesonide; Chemokine CCL17; Chemokine CXCL10; Child; Child, Preschool; Female; Fluticasone; Humans; Lung; Male; Nitric Oxide; Tumor Necrosis Factor-alpha

Allergen-specific immunotherapy (SIT) is the only available potentially curative approach in the management of allergic diseases. Therapies that boost regulatory T cell induction during SIT might further enhance its effectiveness.. The purpose of this study was to assess the effect of montelukast treatment on early clinical and immunologic effects of allergen-specific immunotherapy in children with asthma.. It was a randomized, double-blind, placebo-controlled trial conducted in 36 children with asthma and allergy to house dust mites who required from 400 to 800 microg of inhaled budesonide per day during the 7-month run-in period. Patients were randomly allocated to receive 5 mg montelukast daily (n = 18) or placebo (n = 18) as an addition to inhaled corticosteroid (ICS) treatment during the 3-month build-up phase of SIT, when modification of ICS doses was not allowed. During the 7 months of the maintenance phase of SIT, ICS doses were adjusted to control the asthma symptoms.. After 12 months of SIT, a reduction of the median daily ICS dose, necessary to control asthma symptoms, was 16.7% grater in patients from the placebo group than in patients from the montelukast group. Intervention with montelukast significantly impaired the induction of regulatory T lymphocytes. During the build-up phase of SIT, patients in the placebo group frequently experienced an increase in asthma symptoms leading to exclusions from the per protocol population.. Our study failed to show a beneficial effect of montelukast on SIT. In fact, quite the opposite occurred: compared with placebo, montelukast intervention led to less effectiveness of SIT.

Topics: Acetates; Administration, Inhalation; Animals; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Budesonide; Chemotherapy, Adjuvant; Child; Cyclopropanes; Desensitization, Immunologic; Double-Blind Method; Follow-Up Studies; Humans; Lymphocyte Activation; Pyroglyphidae; Quinolines; Sulfides; T-Lymphocytes, Regulatory; Time Factors

In a double-blind, randomized study, 136 children, 5-10-y-old, with newly detected persistent asthma received budesonide (BUD) 400 microg twice daily for 1 mo and thereafter 200 microg twice daily for 5 mo. Thereafter, 50 children were treated with BUD 100 microg twice daily, whereas 44 children used BUD as needed for 1 y; an additional 42 children received disodium cromoglycate (DSCG). Asthma exacerbations were treated with BUD for 2 wk in a dose of 400 microg twice daily in all groups. In this secondary analysis, bone mineral density (BMD) of the lumbar vertebrae was measured before and after the 18-mo treatment. Compared with DSCG, regular BUD treatment resulted in a significantly smaller increase in BMD (0.023 versus 0.034 g/cm; p = 0.023) and height (7.75 versus 8.80 cm; p = 0.001). Periodic treatment did not affect BMD. No intergroup differences were observed when BMD data were adjusted for changes in height. Daily BUD treatment in prepubertal children may slow down the increment in BMD and standing height. This was not observed in children receiving BUD periodically after the initial regular BUD treatment. The correlation between height and BMD suggests that following children's height might afford an estimation of inhaled corticosteroid effects on bone.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Double-Blind Method; Humans; Lumbar Vertebrae; Male

The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear.. The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted) who previously demonstrated a > or = 30% fall in forced expiratory volume in 1 second (FEV1) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 microg), formoterol (4.5 microg), salbutamol (2 x 100 microg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day.. In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1.. A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Netherlands; Time Factors; Treatment Outcome; Young Adult

International asthma guideline recommends inhaled corticosteroids therapy for children of all ages as the first controller. However, in some less developed parts of the world, ketotifen, an old inexpensive medicine with antihistaminic and anti-allergic reactions, has been found to be the most favored prophylactic agents.. To compare the efficacy and safety of ketotifen and inhaled budesonide in asthmatic children aged 8 months to 14 years at Banpong Hospital, located 80 km south from Bangkok.. Children who had been admitted with acute asthmatic attack in 2008 at Banpong Hospital and had > 3 episodes of wheeze with good response to nebulized bronchodilators were randomized into two groups. Ketotifen group (n = 16) were given oral ketotifen 0.5 mg or 1 mg twice daily depending on age. Budesonide group (n = 14) were given as inhaled budesonide 200 microg (MDI) twice daily. Caregivers recorded children's asthmatic symptoms and nebulized treatments in diaries every day. The enrolled children received these two treatment regimens and were followed up for 26 weeks.. Number of ER visits decreased significantly after both treatments (p < 0.005). The percentage of children with reduction in ER visits was comparable between ketotifen and budesonide (p = 0.16). Ketotifen group also demonstrated a reduction in days of hospital stay (p < 0.05). Budesonide treatment resulted in more symptom-free days (p < 0.05). Both medications were well tolerated and safe. The only demonstrated side effect of ketotifen was weight gain. The growth rate in height for both groups did not differ.. Both ketotifen and inhaled budesonide are effective, safe, and well-tolerated in the prevention of asthma exacerbation in children particularly in the country with limited resource.

Topics: Administration, Inhalation; Adolescent; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Infant; Ketotifen; Male; Thailand; Treatment Outcome

Inhaled corticosteroid (ICS)/long-acting beta(2)-agonist (LABA) combinations are the preferred maintenance therapy for adult asthma patients uncontrolled by ICS alone. Supporting data are largely from mixed populations of adolescents and adults, although ICS/LABA combinations are not approved for adolescents in all countries. This analysis evaluates overall asthma control in asthma patients aged >or=16 years receiving ICS/LABA combinations.. This was a post hoc analysis of asthma patients aged >or=16 years in a randomized, double-blind/open-label extension, parallel-group study. Patients received fixed maintenance-dose budesonide/formoterol (Symbicort Turbuhaler), fixed maintenance-dose salmeterol/fluticasone propionate (Seretide/Advair/Adoair Diskus) or adjustable maintenance-dose budesonide/formoterol. Patients used terbutaline or salbutamol for as-needed reliever medication. The primary efficacy variable was the odds of having a well controlled asthma week during the randomized treatment period.. ICS/LABA regimens were well tolerated and efficacious, and the odds for achieving a well controlled asthma week did not differ between groups in this sub-analysis. The number of exacerbations was similar between fixed-dose regimens; however, there were trends toward fewer exacerbations requiring hospitalization/emergency room treatment in the fixed- and adjustable maintenance-dose budesonide/formoterol groups (three and two events, respectively) than in the fixed-dose salmeterol/fluticasone propionate group (eight events). Improvements in forced expiratory volume in 1 second (FEV(1)) were small but significantly greater with fixed-dose budesonide/formoterol versus fixed-dose salmeterol/fluticasone propionate.. This post hoc analysis supports the use of ICS/LABA combinations in adults aged >or=16 years.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Three fixed maintenance-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) combinations for the treatment of asthma are currently available: salmeterol/fluticasone propionate (Seretide/Advair/Adoair) budesonide/formoterol (Symbicort) and beclometasone/formoterol (Foster). All of these combinations have proven efficacy in terms of controlling symptoms, improving lung function and reducing the rate of exacerbations compared with ICSs and LABAs administered separately. Budesonide/formoterol is also approved for use as maintenance and reliever therapy in a number of countries (Symbicort SMART). Many of the studies supporting the use of budesonide/formoterol combination therapies have included populations of adolescents and adults aged >11 years.. This post hoc analysis compared the efficacy of ICS/LABA fixed maintenance-dose treatment with budesonide/formoterol and salmeterol/fluticasone propionate versus budesonide/formoterol maintenance and reliever therapy in patients with persistent asthma aged > or =16 years.. Following 2-weeks' run-in, 2866 adults aged > or =16 years were randomized to: fixed maintenance-dose budesonide/formoterol 640 microg/18 microg per day, salmeterol/fluticasone propionate 100 microg/500 microg per day plus terbutaline as needed, or budesonide/formoterol 320 microg/9 microg per day plus additional inhalations as needed (budesonide/formoterol maintenance and reliever therapy). Outcome measures included time to first severe asthma exacerbation (primary outcome) and number of severe asthma exacerbations.. Budesonide/formoterol maintenance and reliever therapy prolonged time to first severe exacerbation versus budesonide/formoterol and salmeterol/fluticasone propionate fixed maintenance dose (p = 0.037 and p = 0.0089, respectively). Compared with salmeterol/fluticasone propionate fixed maintenance-dose treatment, fixed maintenance-dose budesonide/formoterol reduced the risk of hospitalizations/emergency-room visits by 28% (relative rate [RR] 0.72; 95% CI 0.53, 0.98; p = 0.034) and budesonide/formoterol maintenance and reliever therapy by 37% (RR 0.63; 95% CI 0.46, 0.87; p = 0.0043). All treatments provided similar improvements in lung function, asthma control days and asthma-related quality of life.. Budesonide/formoterol fixed maintenance dose or maintenance and reliever therapy provides similar improvements in current asthma control and reduces the future risk of hospitalizations/emergency-room treatments versus salmeterol/fluticasone propionate fixed maintenance-dose treatment, providing additional clinical benefit to asthma patients aged > or =16 years.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Emergency Service, Hospital; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Hospitalization; Humans; Kaplan-Meier Estimate; Lung; Male; Middle Aged; Proportional Hazards Models; Quality of Life; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose. A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting β(2)-agonist were randomised to budesonide/formoterol 160/4.5 μg, one (1 × 2) or two (2 × 2) inhalations b.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2 × 2 versus 1 × 2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2 × 2. The mean daily ICS doses were 737 and 463 μg in the 2 × 2 and 1 × 2 groups, respectively. In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Asthma; Budesonide; Drug Administration Schedule; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Research Design; Time Factors

Topics: Adult; Anti-Allergic Agents; Asthma; Budesonide; Cataract; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Humans; Infant; Male; Nedocromil; Risk Factors

Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in children with asthma.. To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma and whether IUS modifies the response to treatment with inhaled corticosteroids (ICSs).. To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma, we performed a repeated-measures analysis of methacholine PC(20) data from the Childhood Asthma Management Program, a 4-year, multicenter, randomized, double-masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the long-term efficacy of ICS with mast cell stabilizing agents or placebo.. Although improvement was seen in both groups, children with asthma and IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared with unexposed children (P = .01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC(20) compared with untreated children (1.25-fold increase; 95% CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65-1.68; P = .88).. In utero smoke exposure reduces age-related improvements in airway responsiveness among children with asthma. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Child; Child, Preschool; Female; Functional Residual Capacity; Health; Humans; Longitudinal Studies; Male; Pregnancy; Prenatal Exposure Delayed Effects; Time Factors; Tobacco Smoke Pollution; Treatment Outcome

To assess efficacy/tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide pMDI (primary) and twice-daily budesonide/formoterol (secondary) in children/adolescents with asthma stabilized with twice-daily budesonide/formoterol.. This 12-week multicenter, double-blind randomized controlled study (www.clinicaltrials.gov identifier NCT00646321) included 521 patients aged 6 to 15 years with mild/moderate persistent asthma. Patients stabilized during a 4- to 5-week run-in with twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily) received twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily), once-daily budesonide/formoterol pMDI 80/4.5 microgx2 inhalations (160/9 microg daily; evening), or once-daily budesonide pMDI 80 microgx2 inhalations (160 microg daily; evening).. Once- or twice-daily budesonide/formoterol was more effective than budesonide for evening peak expiratory flow (primary variable) at the end of the 24-hour once-daily dosing interval (P

Topics: Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Ethanolamines; Female; Formoterol Fumarate; Humans; Male

We have previously shown that inhaled corticosteroids activate indoleamine 2, 3-dioxygenase (IDO) activity through increased IL-10 secretion. Statins might enhance the anti-inflammatory effects of corticosteroids.. In a double-blind study we added simvastatin to patients with mild asthma receiving a low dose of inhaled budesonide and evaluated sputum eosinophil counts, IL-10 secretion, and IDO activity, as well as their putative signaling pathways.. After a 2-week run-in period without treatment, 50 asthmatic patients were treated with 200 μg of budesonide and randomly assigned to either 10 mg of simvastatin or matched placebo for 8 weeks. Inflammation was evaluated through eosinophil counts, secretory signaling molecules, and immunocytochemistry of macrophages in sputum.. Sputum eosinophil percentages were reduced significantly by the combined therapy with budesonide and simvastatin compared with budesonide alone (P = .02). Corticosteroids activated glucocorticoid-induced TNF receptor ligand, which induces activation of p52 through the noncanonical nuclear factor κB pathway, leading to the increased transcription and activation of IDO. Simvastatin enhanced corticosteroid-activated noncanonical nuclear factor κB-dependent induction of IDO by activating type I interferons and also enhanced the effect of corticosteroid on IL-10 release.. A statin enhances the anti-inflammatory effect of an inhaled corticosteroid in asthma, and this was mediated through the alteration of IDO activity in macrophages.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Enzyme Induction; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Macrophages; Male; Middle Aged; Simvastatin; Treatment Outcome

The modern treatment guideline of bronchial asthma recognize that combination of long acting beta2-agonists and inhaled glucocorticoids, enables better control of inflammation and symptoms of asthma than inhaled glucocorticoids only. These guidelines recommended that patients are educated to adjust their medication to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication to asthma symptoms Therefore, combination of formoterol and budesonide can be delivered at different dosing level without the need to change inhalers. This study examined whether asthma control improved if patients adjusted the maintenance doses(AMD) ofbudesonide/formoterol (Symbicort, 80/ 4.5 microg and 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. This was a prospective open randomized trial carried out in five teaching hospitals across Nigeria between 15th July 2002 and 15th July 2003. Patients with bronchial asthma who met the enrollment criteria were randomized to receive either adjustable dosing or fixed dosing for a period of twelve weeks. The results obtained at the start and the end of the study showed that budesonide/formoterol combination effectively achieved and maintained control of asthma. The adjustable dosing achieves more effective control compared to fixed dosing in terms of the number of patients that are redistributed to less severe forms of persistent asthma. The percentage of patients with intermittent asthma increased from 9.3% at randomization to 55.6% at the end of therapy with more patients at the AMD arm of treatment. Also for mild persistent asthma there was an increase from 20.4% to 24.1%. This showed that at the end of treatment, majority (79.7%) of the patients had intermittent and mild persistent asthma. The frequency of use of budesonide/formoterol in the two arms of treatment showed that patients in the adjustable groups used less number of inhalations of budesonide/formoterol for treatment on average of 2.5 inhalations per day compared to those on fixed dosing who used 4 inhalations per day (p = 0.0001). The number of times patients stayed awake because of asthma was noticed to be more reduced at the adjustable arm of treatment but this was of no statistical significance. It is therefore concluded, that budesonide/formoterol combination in a single inhaler is a simple, well tolerat

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Hospitals, Teaching; Humans; Male; Metered Dose Inhalers; Middle Aged; Nigeria; Prospective Studies; Self Care; Severity of Illness Index; Treatment Outcome

The objective of this study was to evaluate the safety and pharmacokinetics of unit dose budesonide (UDB), an aqueous dispersion of submicron-sized budesonide particles, and a commercially available budesonide suspension formulation. This was a randomized, double-blind, active-controlled, 4-period, 4-way crossover trial in 16 healthy, adult volunteers. Subjects received UDB 0.24, 0.12, and 0.06 mg or commercial budesonide 0.25 mg via a jet nebulizer. T(max) was significantly (p<0.05) earlier for UDB 0.06, 0.12, and 0.24 mg (4.5+/-3.3, 3.1+/-1.5, 3.7+/-1.5 min) vs. commercial budesonide (9.1+/-7.1 min). C(max) was significantly (p<0.05) higher for UDB 0.24 mg vs. commercial budesonide 0.25 mg (434.5+/-246.9 pg/mL vs. 303.5+/-177.4 pg/mL) but not between UDB 0.12 mg (239.9+/-140 pg/mL) and commercial budesonide 0.25 mg (p=0.448). AUC(0-infinity) was marginally, but significantly lower for UDB 0.24 mg than commercial budesonide 0.25 mg. AUCs for UDB 0.12 mg were lower than commercial budesonide 0.25 mg. UDB 0.24 mg was absorbed more rapidly and achieved higher peak concentrations than commercial budesonide 0.25 mg, but had a lower AUC(0-infinity). UDB 0.12 mg also was absorbed more rapidly but had lower C(max) and AUCs than commercial budesonide 0.25 mg.

Topics: Administration, Inhalation; Adult; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Chemistry, Pharmaceutical; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Nebulizers and Vaporizers; Particle Size; Young Adult

Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home.. We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma.. Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks.. Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group.. Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.

Topics: Administration, Inhalation; Adolescent; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Feasibility Studies; Female; Glucocorticoids; Humans; Male; Monitoring, Ambulatory; Netherlands; Nitric Oxide; Patient Satisfaction; Prospective Studies; Quality of Life; Treatment Outcome

To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma.. To determine whether severe asthma exacerbations are associated with a persistent decline in lung function.. The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5-66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function.. There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator FEV(1) % predicted from baseline to the end of the study, in patients who did or did not experience a severe exacerbation was -6.44% and -2.43%, respectively (P < 0.001). A significant difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV(1) % predicted in patients who did or did not experience a severe exacerbation was -2.48% and -1.72%, respectively (P = 0.57). The difference in magnitude of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042).. Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline.

Topics: Adolescent; Adult; Aged; Asthma; Budesonide; Child; Child, Preschool; Disease Progression; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Treatment Outcome; Young Adult

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure. In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 microg Turbuhaler, budesonide 160 microg/formoterol 4.5 microg Turbuhaler and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD(20)), exhaled nitric oxide fraction (F(eNO)), sputum eosinophils and prostaglandin D(2), and diary card recordings of symptoms (on a scale of 0-10), short-acting beta(2)-agonist use and evening forced expiratory volume in one second (FEV(1)). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD(20): 397 (98) microg before versus 168 (82) microg after), F(eNO) (mean+/-sd 46+/-31 ppb before versus 73+/-46 ppb after) and asthma symptom score (mean+/-sd 0.39+/-0.55 before versus 0.68+/-0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV(1). Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation. Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Least-Squares Analysis; Male; Middle Aged; Respiratory Function Tests; Sputum; Treatment Outcome

To determine whether long-term, continuous use of inhaled anti-inflammatory medications affects asthma outcomes in children with mild to moderate asthma after use is discontinued.. Of the 1041 participants in the Childhood Asthma Management Program randomized clinical trial, 941 (90%) were followed to determine whether 4.3 years of twice-daily budesonide or nedocromil administration (each compared with placebo) affected subsequent asthma outcomes during a 4.8-year posttrial period in which treatment was managed by the participants' physicians.. The groups treated continuously during the trial with either budesonide or nedocromil did not differ from the group given placebo in terms of lung function, control of asthma, or psychological status at the end of 4.8 years of posttrial follow-up. However, the decreased mean height in the budesonide group relative to the placebo group at the end of the trial (1.1 cm; P = .005) remained statistically significant (0.9 cm; P = .01) after an additional 4.8 years and was more pronounced in girls (1.7 cm; P = .001) than in boys (0.3 cm; P = .49). Participants in all groups used inhaled corticosteroids during 30% of the posttrial period.. Clinically meaningful improvements in the control of asthma and in airway responsiveness achieved during continuous treatment with inhaled corticosteroids do not persist after continuous treatment is discontinued.

Topics: Adolescent; Anti-Inflammatory Agents; Asthma; Body Height; Bronchodilator Agents; Budesonide; Drug Utilization; Emergencies; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Nedocromil; Outcome Assessment, Health Care; Prednisone; Severity of Illness Index; Sex Factors; Vital Capacity

To evaluate the efficacy of add-on montelukast on asthma control and allergic rhinitis symptoms in asthmatic patients still symptomatic with chronic treatment with inhaled corticosteroid and long-acting beta(2) agonist (ICS/LABA), irrespective of the dose.. This 2-month, open-label, real-life, multicentre, observational study was undertaken by 499 general practitioners in Belgium. Patients (>or= 4 years old) with uncontrolled asthma despite fluticasone/salmeterol or budesonide/formoterol therapy had oral montelukast 4, 5, or 10 mg daily added to their therapy, depending on the registered dose for their age. Asthma control, assessed by the 6-item Juniper Asthma Control Questionnaire (ACQ) was recorded at baseline and after 2 months of treatment with montelukast and the patients' global evaluation of asthma was also recorded at the end of the study. Concomitant allergic rhinitis symptoms were evaluated according to the patients' perception.. A total of 5769 patients were eligible for analysis. Addition of montelukast was associated with significant decrease in mean (SD) ACQ score (from 1.97 [0.77] at baseline to 1.05 [0.69] after add-on treatment, p < 0.001). There was also a significant improvement in all individual symptoms of the ACQ score (p < 0.001). After 2 months, 89% of the patients reported global improvement of their asthma, with a good correlation between patients' global evaluation and change in ACQ scores. Of the 2442 patients who reported allergic rhinitis symptoms at baseline, 91% showed a global improvement of their asthma symptoms and 82% in their rhinitis symptoms after adding montelukast.. This open-label observational study showed an improvement, after 2 months of add-on therapy with montelukast, in both asthma and allergic rhinitis symptoms in patients not adequately controlled on a fixed association of ICS/LABA.

Topics: Acetates; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Belgium; Budesonide; Cyclopropanes; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides; Surveys and Questionnaires

Few studies have compared the effects of immunotherapy and inhaled steroids. The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy.. To compare the effects of inhaled budesonide and sublingual immunotherapy (SLIT) in mild persistent asthma for up to 5 years.. Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open randomized controlled trial. After a run-in season, they were randomized to either budesonide, 800 microg/d, in the pollen season or continuous grass SLIT for 5 years. All patients received rescue medications. Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years. In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed.. Fifty-one patients were enrolled and 46 completed the study. The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups, but the improvement was greater in the SLIT patients at 3 and 5 years. The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group, and the difference vs the budesonide group was always significant. In the SLIT group vs the budesonide group, a statistically significant decrease of nasal eosinophils was found at 3 and 5 years (P < .01). The bronchial hyperresponsiveness improved significantly only in the SLIT group.. In patients with grass pollen-induced asthma, in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness.

Topics: Administration, Inhalation; Administration, Sublingual; Adolescent; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Desensitization, Immunologic; Female; Follow-Up Studies; Humans; Male; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Young Adult

To estimate the direct and indirect costs of severe asthma and the economic impact of its management to low-income families in Salvador, Brazil.. One hundred and ninety-seven patients with severe asthma and referred to a state-funded asthma center providing free treatment were evaluated. At registration, they were asked about family cost-events in the previous year and had a baseline assessment of lung function, symptoms and quality of life. During the subsequent year, they were reassessed prospectively.. One hundred-eighty patients concluded a 12-month follow-up. Eighty-four percent were female patients, and the median family income was US$ 2955/year. Forty-seven percent of family members had lost their jobs because of asthma. Total cost of asthma management took 29% of family income. After proper treatment, asthma control scores improved by 50% and quality of life by 74%. The income of the families increased by US$ 711/year, as their members went back to work. The total cost of asthma to the families was reduced by a median US$ 789/family/year. Consequently, an annual surplus of US$ 1500/family became available.. Family costs of severe asthma consumed over one-fourth of the family income of the underprivileged population in a middle-income country. Adequate management brings major economic benefit to individuals and families.

Topics: Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Brazil; Bronchodilator Agents; Budesonide; Cost of Illness; Ethanolamines; Family; Female; Fenoterol; Formoterol Fumarate; Humans; Male; Middle Aged; Poverty; Quality of Life; Rhinitis

A cyclodextrin solution formulation of budesonide has been developed.. To assess the anti-inflammatory effect of a novel soluble formulation of nebulized budesonide compared with the present suspension formulation based on a 1:4 nominal dose ratio.. Seventeen mild to moderate asthmatic patients were randomized to receive 120 microg of Capsitol-Enabled Budesonide Inhalation Solution (CBIS) twice daily or 500 microg of budesonide suspension (Pulmicort Respules) twice daily via nebulizer for 2 weeks in a crossover manner. Methacholine challenge, fractionated exhaled nitric oxide (NO) measurement, spirometry, and 10-hour overnight urinary creatinine-corrected cortisol measurement were conducted at baseline and after each treatment.. Neither CBIS nor Pulmicort significantly improved the provocation concentration of methacholine that caused a decrease in FEV1 of 10% as change from baseline (doubling dilution changes, 0.82; 95% confidence interval [CI], -0.08 to 1.72; P = .08; and 0.86; 95% CI, -0.61 to 2.32; P = .41, respectively). Both CBIS and Pulmicort suppressed exhaled NO from baseline (geometric mean fold ratios: for tidal NO, 0.70; 95% CI, 0.55-0.90; P = .006; and 0.62; 95% CI, 0.50-0.76; P < .001, respectively; for bronchial flux, 0.73; 95% CI, 0.56-0.95; P = .02; and 0.54; 95% CI, 0.39-0.74; P < .001, respectively). Alveolar NO was significantly suppressed by CBIS (geometric mean fold ratio, 0.33; 95% CI, 0.13-0.85; P = .02) but not by Pulmicort (0.66; 95% CI, 0.25-1.76; P = .81). The mean (SEM) nebulization time for CBIS was 84 (3.0) seconds and for Pulmicort was 303 (19) seconds (P < .001). There were no differences between CBIS and Pulmicort for any other outcome.. There are no significant differences between formulations for any inflammatory outcome. CBIS has a shorter nebulization time and is given at a quarter of the nominal dose of Pulmicort.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Cyclodextrins; Dosage Forms; Female; Humans; Male; Middle Aged; Severity of Illness Index; Solubility; Young Adult

TPI 1020 is a novel compound with potential for anti-neutrophil effects. TPI 1020 exerts its effects by a dual mechanism of action involving corticosteroid activity and controlled donation of nitric oxide.. We assessed the safety, pharmacodynamic and pharmacokinetic activity of ascending doses of TPI 1020 compared to budesonide in asthma.. Smokers with mild asthma (n=27) were randomized to receive either 600mcg of TPI 1020 (n=13) or 400mcg of budesonide (n=14) bid for 2weeks followed by 1200 and 800mcg bid, respectively, for an additional week.. There was no serious adverse event and all but one adverse event were mild or moderate (severe headache with budesonide). Patients receiving TPI 1020 reported three-fold fewer treatment-emergent AEs (n=13) than those receiving budesonide (n=39). TPI 1020 had similar effects as budesonide on FEV(1), PEF, rescue medication, asthma scoring system, methacholine response, sputum eosinophils and exhaled NO. Sputum neutrophils (%) tended to decrease more with TPI 1020 (32.6% decrease versus 3.7% increase for budesonide); the decrease occurring only in patients with high neutrophils at baseline. A significant difference favoring TPI 1020 was noted for CRP. Budesonide caused a statistically significant decrease in 24h urinary free cortisol over 22days (median of 4.4-2.8mcg/ml, p=0.01) whereas TPI 1020 had no such effect (4.4-5.8mcg/ml), suggesting lower systemic corticosteroid exposure following TPI 1020 treatment.. TPI 1020 appears safe in asthmatic smokers and warrants further investigation in respiratory conditions.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Neutrophil Activation; Nitric Oxide; Sputum; Treatment Outcome; Young Adult

Budesonide/formoterol maintenance and reliever therapy maintains asthma control and reduces exacerbation frequency compared with higher fixed-dose combination regimens. Its effects on eosinophilic airway inflammation and structure are unknown.. We sought to compare the effects of budesonide/formoterol 200/6 microg twice daily plus as-needed with budesonide/formoterol 800/12 microg twice daily on airway eosinophils and remodeling.. This 52-week, parallel-group, randomized, double-blind study of 127 asthma patients who were symptomatic despite therapy compared (1) the change between induced sputum percent eosinophils at baseline and the geometric mean of 4 on-treatment values and (2) the change in endobronchial biopsy eosinophil counts pre- and post-treatment.. Mean daily doses of budesonide/formoterol were 604/18 microg in the maintenance and reliever therapy group and 1,600/24 microg in the high fixed-dose group. In the former, the geometric mean percent sputum eosinophils remained unchanged (1.6% to 1.9%), whereas biopsy specimen subepithelial eosinophils increased (6.2 to 12.3 cells/mm(2)). Sputum and biopsy eosinophil counts decreased with high fixed-dose treatment (2.2% to 1.2% and 7.7 to 4.8 cells/mm(2), respectively), resulting in significant treatment differences of 0.7% (ratio, 1.8; 95% CI, 1.2-2.8; P = .0038) and 7.5 cells/mm(2) (ratio, 2.9; 95% CI, 1.6-5.3; P < .001), respectively. There were no between-treatment differences in reticular basement membrane thickness, exhaled nitric oxide, exacerbation frequency, or FEV(1).. Compared with fixed-dose combination treatment containing a 4-fold higher maintenance dose of budesonide, budesonide/formoterol maintenance and reliever therapy is associated with higher eosinophil counts, but these remain within the range associated with stable clinical control.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Blood Cell Count; Bronchodilator Agents; Budesonide; Double-Blind Method; Eosinophils; Ethanolamines; Female; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Young Adult

Adenosine monophosphate (AMP) challenge is a diagnostic tool for asthma. The aim of this study is to evaluate the effect of low dose inhaled budesonide (IB) on PC(20)AMP levels. Seventeen stable mild asthmatic patients were prospectively recruited. After initial testing, patients were administered 400 microg of inhaled budesonide. AMP challenge was then repeated at the 12th hour and 5th,15th, 30th, and 90th days of the treatment. AMP challenge resulted in negative in 47% of the patients at 12(-)hour testing. This study suggests that low-dose IB may return airway responsiveness as early as 12 hours and AMP challenge may be effectively used for treatment monitorization.

Topics: Adenosine Monophosphate; Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Budesonide; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Prospective Studies

The recently released handheld In-Check device can be used to measure the peak inspiratory flow rate (PIF) of patients and is reportedly useful in determining whether the PIF is sufficient for using inhaler devices. In this study, we evaluated the effects of instructions for the use of the device and of the device type based on measurements of the PIF in asthma.. One hundred and thirty-five asthmatic patients who used a fluticasone propionate Diskus (FP-DK) or a budesonide Turbuhaler (BUD-TH) were studied.. The PIF was measured by the In-Check device. For patients without a sufficient PIF of 50 l/min, instructions for the use of the device were given, and the device was changed to hydrofluoroalkan-beclomethasone dipropionate (HFA-BDP).. A significant correlation between the PIF and peak expiratory flow rate (p < 0.0001) was found. In 10 patients in whom the PIF did not increase to >50 l/min after instructions, the device was changed to HFA-BDP, which resulted in significant improvements in lung function in terms of the forced expiratory volume in 1 s (p = 0.018), peak expiratory flow (p = 0.038) and the maximum expiratory flow rates at 50% (p = 0.018) and 25% (p = 0.011).. Measurement of the PIF by the In-Check device is useful in the clinical management of asthma, to provide an appropriate device so as to improve lung function.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Inhalation; Male; Middle Aged; Respiratory Function Tests

To assess an effect of long-term administration of one combined inhaled drug containing glucocorticosteroids (GCS) and long-acting beta2-agonists (LABA) on patient compliance.. The trial included 47 patients (14 males and 33 females, mean age 48.8 +/- 13.2 years) with bronchial asthma (BA) of different severity and duration (from 1 month to 42 years). The patients were divided into two groups by BA duration: 20 patients with newly diagnosed BA and 27 patients with a long history of BA. Cooperation was judged by the questionnaire Index of Cooperation in Bronchial Asthma. Control of BA for the last 4 weeks was determined according to Asthma Control Test.. Patients with BA of new onset have low mean rating of compliance. One combined inhaled drug improved compliance in both groups but the improvement was less in patients with new-onset BA. The ACT-test showed that the above inhaled improve control of BA.. Therapy with one combined inhaled drug containing GCS and LABA is highly effective in patients with BA of different severity. This promotes higher compliance and, finally, produces better effect.

Topics: Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Patient Compliance; Respiratory Therapy; Surveys and Questionnaires

To observe the therapeutical effect on allergic rhinitis with asthma by different ways of inhaling corticosteroids.. Ninety patients suffering from allergic rhinitis with asthma were classified into three groups in random and treated with budesonide (BUD) by nasal spray, inhaling and nasal spray-inhaling combined administration for 12 weeks, respectively. The concentration of serum total IgE, eosinophil cationic protein (ECP) and IL-5, pulmonary functions were examined before and after treatment.. The improvement of symptom scores of rhinitis and asthma in three groups were significant (P < 0.05). The concentration of serum total IgE, ECP and IL-5 in three groups decreased greatly after treatment (P < 0.05). There were significant improvement in FEV1, FEV1/FVC and FEF25%-75% in inhaling group before and after treatment (P < 0.05): FEV1 from (2.04 +/- 0.45) L to (2.47 +/- 0.54) L, FEV1/FVC from (72.73 +/- 5.59)% to (75.42 +/- 5.94)% and FEF25%-75% from 1.69 +/- 0.52 to 2.06 +/- 0.77. There was also significant improvement in nasal spray-inhaling combined groups before and after treatment (P < 0.05): FEV1 from (2.32 +/- 0.56) L to (2.76 +/- 0.58) L, FEV1/FVC from (73.80 +/- 4.17)% to (76.04 +/- 4.49)% and FEF25%-75% from 2.09 +/- 0.45 to 2.34 +/- 0.64. The significant difference of FEV1 among the three treatment groups was observed (P = 0.041).. The symptoms of rhinitis and asthma in three groups by three ways of inhaling BUD were greatly improved, no significant difference in symptom scores and serum parameters was found.

Topics: Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Eosinophil Cationic Protein; Female; Humans; Immunoglobulin E; Interleukin-5; Male; Middle Aged; Rhinitis, Allergic, Perennial; Treatment Outcome; Young Adult

Device satisfaction and preference are important patient-reported outcomes to consider when choosing inhaled therapy. A subset of adults (n = 153) with moderate or severe asthma participating in a randomized parallel-group, double-dummy trial that compared the efficacy and safety of 12 weeks' treatment with budesonide delivered via Respimat Soft Mist Inhaler (SMI) (200 or 400 microg bd) or Turbuhaler dry powder inhaler (400 microg bd), completed a questionnaire on patient device preference and satisfaction (PASAPQ) as part of a psychometric validation. As the study used a double-dummy design to maintain blinding, patients used and assessed both devices, rating their satisfaction with, preference for, and willingness to continue using each device. The mean age of patients was 41 years, 69% were female and the mean duration of disease was 16 years. Total PASAPQ satisfaction scores were 85.5 and 76.9 for Respimat SMI and Turbuhaler respectively (p < 0.0001); 112 patients (74%) preferred Respimat SMI and 26 (17%) preferred Turbuhaler. Fourteen subjects (9%) indicated no preference for either inhaler. Willingness to continue using Respimat SMI was higher than that for Turbuhaler (mean scores: 80/100 and 62/100, respectively). Respimat SMI was preferred to Turbuhaler by adult asthma patients who used both devices in a clinical trial setting.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Equipment Design; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Nebulizers and Vaporizers; Patient Preference; Patient Satisfaction; Psychometrics; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Glucocorticoid function is dependent on efficient translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus of cells. Importin-13 (IPO13) is a nuclear transport receptor that mediates nuclear entry of GR. In airway epithelial cells, inhibition of IPO13 expression prevents nuclear entry of GR and abrogates anti-inflammatory effects of glucocorticoids. Impaired nuclear entry of GR has been documented in steroid-non-responsive asthmatics. We hypothesize that common IPO13 genetic variation influences the anti-inflammatory effects of inhaled corticosteroids for the treatment of asthma, as measured by change in methacholine airway hyperresponsiveness (AHR-PC20).. 10 polymorphisms were evaluated in 654 children with mild-to-moderate asthma participating in the Childhood Asthma Management Program (CAMP), a clinical trial of inhaled anti-inflammatory medications (budesonide and nedocromil). Population-based association tests with repeated measures of PC20 were performed using mixed models and confirmed using family-based tests of association.. Among participants randomized to placebo or nedocromil, IPO13 polymorphisms were associated with improved PC20 (i.e. less AHR), with subjects harboring minor alleles demonstrating an average 1.51-2.17 fold increase in mean PC20 at 8-months post-randomization that persisted over four years of observation (p = 0.01-0.005). This improvement was similar to that among children treated with long-term inhaled corticosteroids. There was no additional improvement in PC20 by IPO13 variants among children treated with inhaled corticosteroids.. IPO13 variation is associated with improved AHR in asthmatic children. The degree of this improvement is similar to that observed with long-term inhaled corticosteroid treatment, suggesting that IPO13 variation may improve nuclear bioavailability of endogenous glucocorticoids.

Topics: Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Budesonide; Child; Double-Blind Method; Genetic Variation; Genotype; Haplotypes; Humans; Karyopherins; Linkage Disequilibrium; Nedocromil; Polymorphism, Genetic; Polymorphism, Single Nucleotide

Budesonide/formoterol as single inhaler was developed for treating asthma patients who are not adequately controlled on glucocorticoides alone. The aim of this study was to evaluate efficacy, safety and patient/physician satisfaction of budesonide/formoterol therapy.Total of 268 asthma patients (120 men, mean age 38.8 +/- 37.2 years, and 148 women, mean age 42.2 +/- 32 years) were included in the study. All patients received budesonide/formoterol bid (640 mcg of budesonide and 18 mcg of formoterol daily) during run-in period for three weeks. Patients were followed during 14 weeks at 5 visits. At each visit lung function (FEV1 and PEF) was measured,presence of side affects was recorded and questionnaire was given to patients and physicians to estimate the level of satisfaction with budesonide/formoterol therapy (1 very unsatisfied to 5 very satisfied). Significant improvement was noticed in FEV1, from 76.25% of predicted value to 86.94% (p < 0.01); and in PEF from 380.84 L/min to 442.29 L/min (p < 0.01) in all patients. At the end of the study patients' satisfaction with budesonide/formeterol therapy was significantly improved comparing with satisfaction with previously taken therapy, in average grade, from 2.94 to 4.56 (p < 0.01), and similar results were noticed with physicians' satisfaction, from 2.60 to 4.41 (p < 0.01). Budesonide/formoterol in single inhaler, significantly improved lung function in patients with asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Patient Satisfaction; Young Adult

The goal of asthma therapy is to control symptoms using minimal pharmacologic intervention.. To evaluate the efficacy and tolerability of once-daily budesonide/formoterol vs once-daily budesonide in patients stable with twice-daily budesonide/formoterol.. This double-blind, 12-week study enrolled 619 patients 12 years and older with mild to moderate asthma. After 4 to 5 weeks of twice-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI), 80/4.5 microg x 2 inhalations (320/18 microg/d), stable patients were randomized 1:1:1:1 to 2 inhalations twice daily of budesonide/formoterol pMDI, 80/4.5 microg (320/18 microg/d), or 2 inhalations once daily (evening) of budesonide/formoterol pMDI, 160/4.5 microg or 80/4.5 microg (320/9 microg or 160/9 microg/d), or budesonide pMDI, 160 microg (320 microg/d).. All budesonide/formoterol groups maintained significantly more favorable evening predose forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (PEF), daytime/nighttime asthma symptoms, nighttime rescue medication use, and rescue medication-free days vs budesonide. Variables evaluated during the end of the once-daily dosing interval (evening predose FEV1, evening PEF, daytime asthma symptoms, and daytime rescue medication use) significantly favored twice-daily budesonide/formoterol vs all treatments. Twice-daily budesonide/formoterol demonstrated significantly more favorable results for symptom-free and asthma control days vs all treatments and awakening-free nights vs budesonide. Asthma Quality of Life Questionnaire and Asthma Control Questionnaire results significantly favored twice-daily budesonide/formoterol vs budesonide (P < or = .018). All treatments were well tolerated.. Pulmonary function and asthma control were more effectively maintained with all budesonide/formoterol regimens vs once-daily budesonide and with twice-daily budesonide/formoterol at twice the daily formoterol dose vs both once-daily budesonide/formoterol doses.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Peak Expiratory Flow Rate; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

Previous studies have suggested a reduced benefit from therapy with inhaled corticosteroids (ICSs) in asthmatic patients who smoke. The objective of this post hoc study was to study the effects of low-dose inhaled budesonide on lung function in smokers and nonsmokers with mild persistent asthma.. Adult patients (age, >or= 18 years) in the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study, a 3-year, randomized, placebo-controlled, double-blind study, were stratified according to their smoking habits. The effects on lung function of therapy with budesonide vs placebo were compared in 492 asthmatic patients who smoked habitually and 2,432 nonsmokers.. When treated with placebo, newly diagnosed asthmatic patients who smoke had a greater 3-year decline in post-bronchodilator therapy FEV(1), the change being -263.9 mL (SE, 21.8), when compared with nonsmokers on placebo, which was -180.8 mL (SE, 10.6), the mean difference being -83.1 mL (p < 0.001). Budesonide treatment was associated with a statistically significant 3-year increase in post-bronchodilator therapy FEV(1) in both groups. The effect of budesonide vs placebo was 71.5 mL (p = 0.011) in smokers and 46.5 mL (p = 0.001) in nonsmokers. The corresponding effect in pre-bronchodilator therapy FEV(1) was 118.1 mL (p = 0.002) in smokers and 72.9 mL (p < 0.001) in nonsmokers.. Asthmatic patients who smoke, and are not treated with ICSs, have a greater decline in lung function than asthmatic patients who do not smoke. The benefits of therapy with inhaled budesonide on preventing lung function decline are similar in smokers and nonsmokers with mild persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Severity of Illness Index; Smoking; Treatment Outcome; Young Adult

To study the effectiveness and safety of budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (Symbicort SMART, AstraZeneca, Södertalje, Sweden), a simplified management approach with one inhaler compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma.. Open-label randomised controlled parallel group trial, 6-month treatment.. A total of 908 patients > or = 12 years of age, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting beta(2)-agonist.. Time to first severe asthma exacerbation and number of severe asthma exacerbations.. No difference between groups was seen in time to first severe exacerbation (p = 0.75). Exacerbation rates were low in both groups. A total of 12 patients in the Symbicort SMART group experienced a total of 14 severe asthma exacerbations, and 19 patients in the CBP group experienced a total of 25 severe asthma exacerbations (annual rate 0.07 vs. 0.13 p = 0.09). The mean daily dose of ICS expressed in BDP equivalent was significantly lower in the Symbicort SMART group (including as-needed use) vs. in the CBP group (749 microg vs. 1059 microg; p < 0.0001). Mean scores in Asthma Control Questionnaire, 5 question version improved significantly in the SMART group compared with the CBP group (p = 0.0026). Symbicort SMART and CBP were equally well tolerated. The mean drug cost/patient/month was significantly lower for the patients in the Symbicort SMART group compared with patients receiving CBP (51.3 euros vs. 66.5 euros; p < 0.0001).. In Belgian patients, a simplified regimen using budesonide/formoterol maintenance and reliever therapy was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and significantly lower drug costs.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Costs; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate; Recurrence; Treatment Outcome; Young Adult

Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity.. To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions.. Levels of 3-bromotyrosine and 3,5-dibromotyrosine were measured in sputum supernatants using stable isotope dilution gas chromatography-mass spectrometry in a randomized, placebo-controlled, crossover study of treatment with terbutaline, budesonide, and their combination in patients with persistent asthma. Thirty-four individuals were randomized, and 28 completed the study.. Treatment with budesonide lowered median 3-bromotyrosine levels compared with treatment with placebo, terbutaline, and budesonide-terbutaline (0.24 vs 0.64, 0.62, and 0.43 3-bromotyosine/tyrosine [mmol/mol]; P < .05) and lowered median 3,5-dibromotyrosine levels compared with placebo and terbutaline treatments (0.04 vs 0.11 and 0.07 3,5-dibromotyrosine/ tyrosine [mmol/mol], P < .05). Unlike eosinophil numbers, 3-bromotyrosine and 3,5-dibromotyrosine levels did not increase with terbutaline treatment compared with placebo treatment but were significantly raised when terbutaline was added to budesonide treatment. 3-Bromotyrosine levels correlated significantly with eosinophil cationic protein levels in all groups.. 3-Bromotyrosine and 3,5-dibromotyrosine levels reflect treatment effects in asthma and support previous findings that SABAs impair the anti-inflammatory effects of inhaled corticosteroids. In addition to eosinophil numbers and eosinophil cationic protein levels, these modified tyrosine residues provide useful information about the inflammatory state of the airways.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Humans; Male; Middle Aged; Respiratory Function Tests; Sputum; Terbutaline; Tyrosine; Young Adult

We have shown that expiratory flows increase when expirations are rapidly interrupted in stable asthmatic patients. We hypothesized that a similar increase could be obtained in patients with acute exacerbation of bronchial asthma treated in the Emergency Room. A total of 30 asthmatic patients were randomly allocated into two groups, the study and the control groups. Patients in the study group were connected to a device with an inspiratory line designed to administer pressurized aerosols. The expiratory line passed through a valve completely interrupting flow at 4 Hz, with an open/closed time ratio of 10/3. The control group patients were also connected to the device, but with the valve kept open. Mean expiratory flow at tidal volume (MEFTV) was measured under basal conditions and at 4, 8 and 12 minutes after connecting the patients to the device. All patients received standard treatment throughout the procedure. At all time points MEFTV increased more in the study than in the control group (p < 0.003 by two-way ANOVA). There was no residual effect after disconnection from the device. We conclude that TEFI can rapidly improve expiratory flows in patients with acute exacerbations of asthma, while pharmacologic interventions proceed.

Topics: Acute Disease; Adult; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Flow Rates; Humans; Ipratropium; Male; Time Factors

Using cyclodextrin with budesonide enables it to be formulated in a solution for nebulization.. To observe the effects of a Captisol-enabled budesonide solution (CBIS), 60 microg twice daily, delivered via a nebulizer (eFlow), compared with a conventional budesonide suspension (Pulmicort Respules), 250 microg twice daily, delivered via another nebulizer (LC Plus), using fraction of exhaled nitric oxide (FE(NO)) and overnight urinary cortisol to creatinine ratio as the primary outcomes for efficacy and systemic bioactivity.. A randomized, open-label, crossover study was conducted in 12 children with mild-to-moderate persistent asthma (aged 5-12 years). Measurements were performed after a 2-week steroid washout at baseline and at the end of each 2-week randomized treatment.. The nebulization time was shorter (95% confidence interval [CI], 0.83-5.63 minutes; P = .03) with CBIS (mean, 1.77 minutes) than with Pulmicort Respules (mean, 5.01 minutes). The reduction in FE(NO) with CBIS from pooled baseline was 2.45-fold (95% CI, 1.87-3.21; P < .001); and with Pulmicort Respules, 3.18-fold (95% CI, 2.26-4.47; P < .001). No statistically significant changes from pooled baseline in lung function and overnight urinary cortisol to creatinine ratio were observed with either treatment.. The nebulization time was shorter with CBIS compared with Pulmicort Respules. Both formulations exhibited similar anti-inflammatory activity in terms of reducing FE(NO), with no detectable difference between them when used in a putative microgram nominal dose ratio of 1:4. Neither formulation produced significant adrenal suppression.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Humans; Lung; Nebulizers and Vaporizers; Solutions; Suspensions; Treatment Outcome

Feeling a maintenance therapy work right away may provide positive reinforcement and may offer one way to improve adherence in patients with asthma. Precise measurement is required to accurately compare the presence of this effect across clinical trial treatment groups.. Two randomized, controlled studies tested whether timing of assessment (daily vs weekly, study 1; and predose vs postdose, study 2) influenced patients' reports of whether they can feel a medication working right away (perception), and their satisfaction with this perception (satisfaction). These 2-week US-based multicenter double-blind, parallel-group studies included patients > or = 18 years of age with mild to moderate persistent asthma. In each, patients were randomized to one of two drugs with different onset profiles: budesonide/formoterol pressurized metered-dose inhaler (pMDI) 80/4.5 microg x 2 inhalations (160/9 microg) twice daily or budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. Patients were further randomized to complete previously validated perception and satisfaction questions in a cross-over fashion, either daily and weekly (N = 123) or predose and postdose (N = 134). Patient surveys also assessed perceptions of the onset of effect of medication and their value of these perceptions.. No significant differences were observed in patients' reports of perception, either daily versus weekly or predose versus postdose. A statistically significant difference in satisfaction was found in study 1 only, favoring weekly recall (p < 0.05), with sensitivity analysis showing no difference by treatment group (p = 0.162). Across both studies, most patients (87%) who perceived their inhaler working right away (136 of 157 patients) identified positive airway sensations. Most patients reported that feeling their medication work right away is reassuring and would help them manage their asthma.. Assessment timing has no effect on patient response to the perception of feeling a medication working right away. Differences found in satisfaction levels reported with weekly versus daily recall were consistent across treatment groups, indicating that no bias was introduced in favor of either treatment group. Patients characterized the perception of feeling a maintenance therapy working right away as easier breathing and reported this perception as beneficial to patient self-care.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Medication Adherence; Middle Aged; Patient Satisfaction; Patients; Peak Expiratory Flow Rate; Perception; Reinforcement, Psychology; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult

In a 3-year study, adult patients who recently developed asthma (symptoms for less than 1 year) were treated for 2 years with the inhaled corticosteroid (ICS) budesonide (early therapy) or terbutaline. During the third year of the study, terbutaline-treated patients received budesonide (delayed therapy). Differences in lung function and bronchial responsiveness to histamine were observed between the 2 groups.. We compared the effects of early versus delayed budesonide therapy after a 10-year follow-up period (13 years after the study began) and current real-life data.. Of the original 103 patients, 90 were re-examined 13 years after study initiation. After the third year of the study, all patients had their medications, including the dose of ICS, individually adjusted.. After the follow-up period, lung function was within the normal range for the entire group (all patients); bronchial responsiveness significantly improved compared with baseline data. No statistically significant differences in clinical or functional variables were found between patients given early or delayed budesonide therapy. However, the delayed therapy group had a higher neutrophil count and higher concentrations of eosinophilic cationic protein and myeloperoxidase in induced sputum. This group had also used more asthma medication and hospital days.. Patients with relatively mild asthma who received ICS within 12 months of their first asthma symptoms or after a 2-year delay achieved equally good functional control of asthma after 10 years of individualized therapy. However, the delayed therapy group exhibited slightly less optimal disease control and more signs of airway inflammation.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Follow-Up Studies; Humans; Lung; Male; Middle Aged; Sputum; Terbutaline

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Heterozygote; Homozygote; Humans; Receptors, Adrenergic, beta-2

To compare the cost-effectiveness of budesonide/formoterol in a single inhaler used as Maintenance and Reliever Therapy (SMART) versus fixed higher-dose budesonide/formoterol plus as-needed terbutaline reliever (FHDBF) or fixed dose fluticasone/salmeterol plus as-needed terbutaline reliever (FDFS) in controlling asthma in adults and adolescents.. An economic evaluation was conducted by applying Canadian costs to the results of a large (N=3,335) international randomized, double-blind, controlled trial in which health resource utilization was prospectively collected. Although no Canadian subjects were enrolled in this clinical trial, it was assumed that the results would apply to Canadian patients. Primary outcome measurements included time to first exacerbation and the number of severe exacerbations. Costs included direct medical costs (physician/emergency room visits, hospitalizations, asthma drug costs) and productivity (absenteeism). The time horizon was six months, which corresponded to the duration of the trial. Prices were obtained from 2006 Canadian sources. Both healthcare and societal perspectives were considered. Deterministic univariate sensitivity analyses were conducted.. In the clinical trial, SMART was superior to FHDBF and FDFS with respect to total number of severe exacerbations (RR 0.72; 95% CI 0.57, 0.90; p=0.0048; RR 0.61; 95% CI 0.49, 0.76; p<0.001, respectively). Exacerbation rates (reported as events per patient per 6 months) were 0.12 for SMART, 0.16 for FHDBF, and 0.19 for FDFS. All treatments provided similar improvements in lung function, asthma control days and asthma-related quality of life. The mean cost per patient per 6 months was $545 in the SMART arm versus $690 in the FHDBF arm and $842 in the FDFS arm from the healthcare perspective; and $676 for SMART, $838 for FHDBF, and $954 for FDFS from the societal perspective. SMART was dominant (more effective, less expensive) in the base case analysis from both the healthcare and societal perspectives. The results were robust under sensitivity testing.. The SMART strategy, which allows budesonide/formoterol to be used as both maintenance and reliever medication, is dominant over the alternate strategies of fixed higher dose budesonide and formoterol plus as-needed terbutaline or fixed dose salmeterol and fluticasone plus as-needed terbutaline.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Canada; Child; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prospective Studies; Quality of Life; Salmeterol Xinafoate; Severity of Illness Index; Terbutaline

Adding a long-acting beta(2)-agonist to inhaled corticosteroids (ICS) for asthma treatment is better than increasing ICS dose in improving clinical status, although there is no consensus about the impact of this regimen on inflammation. In this double-blind, randomized, parallel group study, asthmatics with moderate to severe disease used budesonide (400 mcg/day) for 5 weeks (run-in period); then they were randomized to use budesonide (800 mcg/day--BUD group) or budesonide plus formoterol (400 mcg and 24 mcg/day, respectively--FORMO group) for 9 weeks (treatment period). Home PEF measurements, symptom daily reporting, spirometry, sputum induction (for differential cell counts and sputum cell cultures), and hypertonic saline bronchial challenge test were performed before and after treatments. TNF-alpha, IL-4 and eotaxin-2 levels in the sputum and cell culture supernatants were determined. Morning and night PEF values increased in the FORMO group during the treatment period (p<0.01), from 435+/-162 to 489+/-169 and 428+/-160 to 496+/-173 L/min, respectively. The rate of exacerbations in the FORMO group was lower than in the BUD group (p<0.05). Neutrophil counts in sputum increased in both groups (p<0.05) and leukocyte viability after 48 h-culture increased in the FORMO group (p<0.05). No other parameter changed significantly in either group. This study showed that adding formoterol to budesonide improved home PEF and provided protection from exacerbations, although increase of leukocyte viability in cell culture may be a matter of concern and needs further investigation.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Cytokines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Failure

Combination therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs), or treatment with high doses of ICSs alone improves asthma control when therapy with low-dose ICSs is not sufficient. However, it is not known which of these treatment options is more effective in sustaining asthma control.. To evaluate the effect of increasing the ICS dosage vs adding LABAs on the time spent with well-controlled asthma or poorly controlled asthma.. Post hoc analysis of the Formoterol and Corticosteroid Establishing Therapy study, which compared a fourfold increase in the budesonide dose with and without formoterol.. Time with well-controlled asthma was improved by 19% (95% confidence interval [CI], 3 to 35%; p = 0.017) by adding formoterol, 24 microg/d, to therapy with budesonide, 200 microg/d, compared to 2% (95% CI, -9 to 12%; p = 0.76) with therapy with budesonide, 800 microg/d, alone. Time with well-controlled asthma was further improved by 29% (95% CI, 13 to 47%; p < 0.001) by adding formoterol to therapy with budesonide, 800 microg/d. Time with poorly controlled asthma was significantly reduced using the same interventions by 43% (95% CI, 25 to 57%), 22% (95% CI, 7 to 44%), and 50% (95% CI, 30 to 64%), respectively. Adding formoterol to budesonide was significantly more effective in increasing time with well-controlled asthma when compared to increasing the budesonide dose fourfold (increase, 16%; 95% CI, 1 to 33%; p = 0.035), with a trend for a greater reduction in time with poor control (decrease, 21%; 95% CI, -5 to 42%).. The addition of formoterol to therapy with low-dose budesonide increases the probability of well-controlled asthma compared to a substantial increase in the dose of an ICS.

Topics: Adrenergic beta-Agonists; Adult; Asthma; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Treatment Outcome

To evaluate direct asthma-related costs in Swedish primary care in a real-life setting.. 12-month open-label study.. Swedish primary care in a real-life setting.. 1776 patients with persistent asthma.. Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months.. The primary endpoint was direct asthma-related healthcare costs.. Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001).. This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Drug Therapy, Combination; Ethanolamines; Female; Follow-Up Studies; Formoterol Fumarate; Health Care Costs; Humans; Male; Middle Aged; Quality of Life; Terbutaline; Treatment Outcome

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Double-Blind Method; Female; Glaucoma; Humans; Intraocular Pressure; Male; Prospective Studies; Time Factors

The role of inhaled corticosteroids in the treatment of acute asthma exacerbations in children is controversial. This study compared the effect of inhaled budesonide and inhaled fluticasone in controlling acute asthma exacerbations in young children at home.. In a quasi-randomized crossover design, children aged 5 months to 5 years with severe recurrent asthma episodes were treated either with inhaled budesonide 200 mcg or inhaled fluticasone 125 mcg delivered with a similar spacer. At the onset of asthma exacerbations, 2 puffs of inhaled terbutaline followed by inhaled budesonide or fluticasone was administered using one of the following treatment protocols: 1 4-day protocol for a relatively mild exacerbation; 2 8-day protocol for exacerbations that were more severe or uncontrolled by the 4-day protocol; and 3 8-day protocol + azithromycin for exacerbations uncontrolled by the 8-day protocol or possibly associated with infection with atypical agents. Children were followed for 2 months after each exacerbation. Good response was defined as the absence of asthma symptoms for at least 2 weeks from completion of treatment.. One hundred children were recruited: 36 were treated with budesonide, 21 with fluticasone, and 44 with both on different occasions. The groups were similar for preliminary data. Good response was noted in 87% of the budesonide group, 85% of the fluticasone group, and 86% of the budesonide/fluticasone group. By protocol, rates of good response were 84%, 83%, and 94% for the 4-day, 8-day, and 8-day+azithromycin treatment protocols, respectively; corresponding symptom-free periods after treatment were 4.0, 4.9, and 4.3 weeks. None of the children received oral corticosteroids.. Acute asthma exacerbations in young children can be effectively controlled at home with the use of high repetitive doses of inhaled budesonide or inhaled fluticasone, initially together with beta(2)-agonists, given at the beginning of the attack, for a period of 4-8 days.

Topics: Acute Disease; Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Drug Therapy, Combination; Female; Fluticasone; Humans; Infant; Inhalation Spacers; Male; Severity of Illness Index; Terbutaline; Treatment Outcome

This study evaluated the efficacy and safety of Budesonide Inhalation Suspension (BIS) nebulazation by mesh nebulizer in children ages 6 months to 4 years with moderate to severe persistent asthma.. This 12-week, randomized, open study involved 30 asthmatic children. They were randomized 3 different nebulizer groups, Pari TurboBoy +LC Plus nebulizer, Pari eMotion and Omron MicroAir NE-22U. BIS administered 0.25 mg once daily (qd). Efficacy was assessed by daily card. Safety was assessed by adverse event, plasma cortisol and growth.. Baseline concentrations of plasma cortisol were significantly high in the group of Omron MicroAir NE-22U compared to other group. Plasma cortisol were decreased significantly at 4 weeks in Omron MicroAir NE-22U compared with baseline, but those in no subjects decreased under normal range. Asthma symptoms were improved significantly from baseline to 12-week.. This study demonstrate that usage of mesh nebulizer in BIS 0.25 mg qd is effective and safe in young asthmatic children.

Topics: Administration, Inhalation; Asthma; Budesonide; Child, Preschool; Female; Glucocorticoids; Humans; Infant; Male; Nebulizers and Vaporizers; Suspensions

Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler (pMDI) has not been evaluated in asthma.. To evaluate time to onset of clinically significant bronchodilation (> or = 15% improvement in forced expiratory volume in 1 second) and patient-perceived onset of effect (OE) in patients previously receiving inhaled corticosteroids.. In two 12-week studies, patients 12 years and older with moderate to severe (study 1; n = 596) and mild to moderate (study 2; n = 480) persistent asthma received budesonide/formoterol pMDI, budesonide pMDI plus formoterol dry powder inhaler (study 1 only), budesonide pMDI, formoterol dry powder inhaler, or placebo. Postdose time to 15% or greater improvement in forced expiratory volume in 1 second and patient-perceived OE (assessed in a subset of patients 18 years and older [study 1, n=553; study 2, n=405]) were evaluated [corrected]. More budesonide/formoterol-treated patients achieved onset of clinically significant bronchodilation within 15 minutes (median, 13 minutes) of administration at randomization vs those taking budesonide or placebo (P < .001). More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away (P < or = .004; end of week 1). Similar results (P < .001) were observed for patient satisfaction with how quickly they felt their medication begin to work (except budesonide/formoterol vs budesonide, study 1 [P = .073]). Time to onset of clinically significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar.. Budesonide/formoterol demonstrated a more rapid onset of clinically significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Surveys and Questionnaires; Time Factors; Treatment Outcome

Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.. We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma.. In the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV(1) of 12% or greater (and 200 mL) after inhaled beta(2)-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.. We identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV(1) values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up.. We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Humans; Male; Nedocromil; Spirometry; Treatment Outcome; Vital Capacity

Clinical trials in children with moderate-to-severe persistent asthma are limited.. We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing.. The budesonide dose (with salmeterol [50 microg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 microg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction.. Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated.. Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma.

Topics: Acetates; Adolescent; Albuterol; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Medication Adherence; Quinolines; Salmeterol Xinafoate; Severity of Illness Index; Sulfides; Time Factors

Assessment of asthma through spirometric analysis in children is challenging because of often normal FEV(1) values.. We used Mead's slope ratio (SR; (dV /dV)/(V /V)) to analyze the shape of the flow-volume loop.. We analyzed the effects of time, albuterol, and budesonide on FEV(1), FEV(1)/forced vital capacity (FVC) ratio, forced expiratory flow from 25% to 75% of expired volume, and Mead's SR both early (between 75% and 50% of FVC, SR61) and late (between 75% and 50% of FVC, SR35) in exhalation in the Childhood Asthma Management Program cohort at baseline, 4 months, and the end of the study in participants who received either inhaled placebo or budesonide twice daily.. In the placebo group both SR61 and SR35 improved over time. Bronchodilator consistently improved both SR61 and SR35, without change in degree of improvement over time. Similarly, in the budesonide group time and bronchodilator each independently improved both SR61 and SR35. At 4 months and the end of the study, patients receiving budesonide had significant improvements in SR61 relative to patients receiving placebo, which was independent of bronchodilator effect. Budesonide and placebo were not different with respect to prebronchodilator or postbronchodilator SR35.. Budesonide-treated patients have less concave flow-volume loops when compared with placebo-treated patients. Time and bronchodilator also make the flow-volume loop less concave. Furthermore, it appears that there are discrete bronchodilator- and corticosteroid-responsive components of airflow obstruction in pediatric asthma.

Topics: Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cohort Studies; Female; Forced Expiratory Flow Rates; Humans; Male; Time Factors; Vital Capacity

Budesonide/formoterol maintenance and reliever therapy has shown its effectiveness as a treatment for moderate-to-severe asthma.. To explore the cost-effectiveness of budesonide/formoterol maintenance and reliever therapy as compared to fixed combination therapies (budesonide/formoterol and salmeterol/fluticasone) with terbutaline as needed in the treatment of asthma in Finland.. Patients without asthma exacerbations during a 6-month period were used as the effectiveness variable in the within-trial economic analysis. Finnish unit costs were applied to pooled resource use data, and multinomial cost-effectiveness plane and acceptability curves were formed based on bootstrapping.. Use of budesonide/formoterol maintenance and reliever therapy significantly reduced the rate of severe asthma exacerbations as compared with a fixed dose of budesonide/formoterol or salmeterol/fluticasone and terbutaline as needed. Total costs over 6 months were 496 euros per patient for those who used the budesonide/formoterol maintenance and reliever therapy treatment model, which was 78-101 euros lower than the cost of fixed combinations of salmeterol/fluticasone or budesonide/formoterol with terbutaline as needed. The results indicate that the budesonide/formoterol maintenance and reliever therapy achieves a high probability (> 93%) of cost effectiveness irrespective of willingness to pay level.. Budesonide/formoterol maintenance and reliever therapy may be considered in the treatment of moderate-to-severe asthma instead of conventional treatment with combination products in view of its good clinical efficacy and a high probability of cost-effectiveness in the Finnish setting. However, a cost-effectiveness analysis with a longer time horizon, more Finnish-specific data, and ICS + short/long-acting inhaled beta(2)-agonist as an additional comparator is still warranted.

Topics: Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Costs and Cost Analysis; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Finland; Formoterol Fumarate; Humans; Male; Middle Aged

Patient-reported outcomes (PROs) are important for evaluating asthma therapy.. To evaluate PROs in adults with moderate to severe persistent asthma receiving budesonide and formoterol administered via 1 pressurized metered-dose inhaler (pMDI).. This 12-week, double-blind, double-dummy, placebo-controlled, multicenter study randomized 596 patients 12 years or older to budesonide/formoterol pMDI 160/4.5 microg x 2 inhalations (320/9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg) + formoterol dry powder inhaler (DPI) 4.5 microg x 2 inhalations (9 microg); budesonide pMDI 160 microg x 2 inhalations (320 microg); formoterol DPI 4.5 microg x 2 inhalations (9 microg); or placebo, each twice daily, after 2 weeks of budesonide pMDI 80 microg x 2 inhalations (160 microg) twice daily. PROs were assessed in 553 patients 18 years or older using the standardized Asthma Quality of Life Questionnaire (AQLQ[S]), Medical Outcomes Survey (MOS) Sleep Scale, Patient Satisfaction With Asthma Medication (PSAM) questionnaire, diary data, and global assessments.. Patients receiving budesonide/formoterol reported significantly greater improvements from baseline on the AQLQ(S) and asthma control variables (based on symptoms and rescue medication use; all P < .001) vs placebo. Clinically important improvements (increase of > or = 0.5 points) from baseline to end of treatment in AQLQ(S) overall scores were achieved by 43.6% of patients receiving budesonide/formoterol vs 22.6% of patients receiving placebo (P = .001). The MOS Sleep Scale scores generally showed no differences among treatment groups. Patients receiving budesonide/formoterol had significantly greater PSAM questionnaire scores and better outcomes on physician-patient global assessments at end of treatment vs placebo (all P < or = .001).. Significantly greater improvements in health-related quality of life and asthma control and greater treatment satisfaction were observed with budesonide/formoterol pMDI vs placebo.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Patient Satisfaction; Quality of Life; Treatment Outcome

Budesonide/formoterol in one inhaler is an established therapy for asthma and chronic obstructive pulmonary disease. The long-term safety and efficacy profile of a novel hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation of budesonide/formoterol was compared with that of budesonide/formoterol in a dry powder inhaler (DPI; Turbuhaler). This multinational, 52-week, randomized, open, parallel-group study included patients aged > or = 12 years with asthma who had a forced expiratory volume in 1s (FEV1)> or = 50% of predicted normal; all patients used inhaled corticosteroids (400-1200 microg/day) and needed additional short-acting beta 2-agonist therapy. Patients were randomized to receive budesonide/formoterol pMDI or DPI 160/4.5 microg, two inhalations twice daily. Safety endpoints included assessment of adverse events and laboratory parameters. Efficacy endpoints included change from baseline in FEV1 and time to first severe asthma exacerbation. Overall, 673 patients (446pMDI, 227DPI) were included. There were no clinically significant differences between treatment groups in the nature, incidence or severity of adverse events or laboratory parameters. The number of patients experiencing adverse events was comparable in the pMDI (332/446 [74%]) and DPI (175/227 [77%]) groups; the most commonly reported adverse event was upper respiratory tract infection. The proportion of patients discontinuing as a result of adverse events was low in both groups (pMDI 12/446 [3%], DPI 2/227 [1%]). Lung function was improved to a similar extent in both groups and there was no detectable difference in time to first severe asthma exacerbation. The novel HFA pMDI formulation of budesonide/formoterol is an equally well tolerated and effective treatment for adults and adolescents with asthma as the budesonide/formoterol DPI.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests

This paediatric asthma study evaluated the efficacy and safety of a novel hydrofluoroalkane pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol versus budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI).. The study was a 12-week, multinational, double-blind trial involving children (aged 6-11 years) with symptomatic asthma on inhaled corticosteroids (375-1000 microg/day), with a history of exercise-induced bronchoconstriction and peak expiratory flow (PEF) > or =50% of predicted. Patients were randomised (two inhalations twice daily) to budesonide pMDI 100 microg, budesonide/formoterol DPI 80/4.5 microg or budesonide/formoterol pMDI 80/4.5 microg. The primary endpoint was change from baseline in morning PEF.. Overall, 622 patients were randomised. Increases in morning PEF with budesonide/formoterol pMDI and budesonide/formoterol DPI were therapeutically equivalent (29.5 versus 30.2l/min, respectively; 95% confidence interval: -6.0 to 4.6; P=0.78, also confirmed by per-protocol analysis). Improvements in secondary efficacy endpoints with both budesonide/formoterol formulations were not significantly different. Significantly greater improvement was achieved with budesonide/formoterol pMDI versus budesonide pMDI for morning PEF (+9.6l/min; P<0.001) and other lung function parameters. The safety profile of budesonide/formoterol pMDI was favourable and similar to that of budesonide/formoterol DPI and budesonide pMDI.. Budesonide/formoterol, administered via the therapeutically equivalent hydrofluoroalkane pMDI or DPI, is an effective and well-tolerated treatment for children with asthma.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Humans; Hydrocortisone; Male; Nebulizers and Vaporizers; Respiratory Function Tests; Therapeutic Equivalency

Previous single-dose crossover studies have established therapeutic equivalence of formoterol when administered at the same nominal dose via a dry powder inhaler (DPI) or pressurized hydrofluoroalkane (HFA) metered-dose inhaler (pMDI). Demonstration of equivalent bronchodilation for formoterol administered as formoterol DPI or combined with budesonide in one pMDI (budesonide/formoterol pMDI) would indicate that the greater clinical efficacy of the budesonide/formoterol pMDI combination is due to the budesonide contribution and not to differences in formoterol formulation or delivery device.. To determine whether the formoterol-related bronchodilatory effects of formoterol DPI and budesonide/formoterol pMDI are similar, despite formoterol formulation and delivery device differences.. This was a multicenter, open-label, five-period crossover study conducted in 201 adult patients with stable asthma. The study included a screening visit, a 7- to 14-day run-in period, during which patients were treated with budesonide pMDI (80 microg per inhalation, two inhalations twice daily), and a randomized treatment period that included five single-day treatment periods, during which patients received single-dose crossover treatments, each of which was separated by a 3- to 14-day washout period. Patients were randomized to five of seven single-dose treatments (one, two, or four inhalations of budesonide/formoterol pMDI 80/4.5 microg; four inhalations of budesonide pMDI 80 microg plus one, two, or four inhalations of formoterol DPI 4.5 microg; or four inhalations of budesonide pMDI 80 microg alone). At clinic visits, the budesonide pMDI dose was coordinated with the budesonide dose delivered via the budesonide/formoterol pMDI such that all patients received a 320-microg dose of budesonide. The primary variable was average forced expiratory volume in 1 s (FEV1) from the area under the curve divided by time from 12-h serial spirometry.. Average 12-h FEV1 values were similar, regardless of delivery device, among treatments with the same nominal formoterol doses and dose-ordered within each device; mean FEV1 values were significantly higher for treatments containing formoterol versus budesonide alone. The formoterol dose potency ratio for budesonide/formoterol pMDI:formoterol DPI (0.97; 95% confidence interval, 0.73-1.27) demonstrated clinical equivalence in bronchodilation at the same formoterol dose.. Budesonide/formoterol pMDI affords equivalent formoterol-related bronchodilatory effects versus formoterol DPI at formoterol doses of 4.5, 9, and 18 microg, indicating that practitioners can expect and patients will experience similar bronchodilation from the same dose of formoterol whether it is delivered as monotherapy via a DPI or as combination therapy with budesonide via one pMDI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Dosage Forms; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Powders

To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and. 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks.. Lung function, the number of exacerbations and growth.. Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth.. Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Double-Blind Method; Drug Administration Schedule; Female; Growth; Humans; Lung; Male; Respiratory Function Tests; Treatment Outcome

Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma, limiting everyday activities important for their physical and social development.. The purpose of this randomized, double-blind, placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment, recommended in childhood asthma, to protect patients from exercise-induced bronchoconstriction.. Children 6 to 18 years of age with atopic asthma were randomized to a 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive daily 200 microg budesonide (twice daily, 100 microg per dose) + 9 microg formoterol (twice daily, 4.5 microg per dose; n = 20); 200 microg budesonide + 5 or 10 mg montelukast (once daily at bedtime; n = 20); 5 or 10 mg montelukast (n = 20); 200 microg budesonide (n = 20); or placebo (n = 20). A standardized treadmill exercise challenge was performed before and after treatment.. Exercise-induced bronchoconstriction, reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise, was significantly diminished after 4 weeks in all active treatment groups, and compared with placebo. Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options.. These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma. Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Exercise; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Hypersensitivity; Male; Quinolines; Sulfides; Treatment Outcome

Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success.. To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids.. Randomised, parallel group, open-label trial.. Forty-four general practices in Nottinghamshire.. Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose.. Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified.. Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Patient Compliance; Quality of Life; Surveys and Questionnaires; Treatment Outcome

The aim of the present study was to compare the effectiveness, safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada. After 2 weeks of usual therapy, 1,538 patients were randomised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 microg twice daily and as needed, or to guideline-based conventional best practice. Severe asthma exacerbations, reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub-study of 115 patients. No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate. There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy (4.4 versus 7.5 events per 100 patients x yr(-1), 41% reduction); however, this did not reach statistical significance. Mean total inhaled corticosteroid dose, reliever use, asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy. Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups. In conclusion, budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice, with significantly lower total inhaled corticosteroid dose and lower cost, while maintaining similar control of eosinophilic inflammation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Treatment Outcome

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic-pituitary-adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6-24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 microg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Male; Nebulizers and Vaporizers; Pituitary-Adrenal System; Recurrence; Respiratory Sounds

To determine the effects of budesonide and formoterol administered via one pressurized metered-dose inhaler (budesonide/formoterol pMDI) on patient-reported outcomes (PROs) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma.. A 12-week, randomized, double-blind, double-dummy, placebo-controlled, multicenter study was conducted in 480 patients aged > or = 12 years with mild-to-moderate persistent asthma. After a 2-week run-in period during which current asthma therapy was discontinued, patients were randomized to receive two inhalations twice daily of budesonide/formoterol pMDI 80/4.5 microg (160/9 microg), budesonide pMDI 80 microg (160 microg), formoterol via dry powder inhaler (DPI) 4.5 microg (9 microg), or placebo.. Analyses included a subpopulation of 405 patients aged > or = 18 years. PROs included the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), the Medical Outcomes Study (MOS) Sleep Scale, the Patient Satisfaction with Asthma Medication (PSAM) questionnaire, and asthma control variables (recorded via electronic diaries), such as asthma symptoms, rescue medication use, and nighttime awakenings due to asthma. Patient and physician global assessments were collected at the end of the study.. Patients aged > or = 18 years receiving budesonide/formoterol pMDI reported significantly greater improvements from baseline in AQLQ overall and domain scores, MOS Sleep Scale domain scores, and asthma control variables than patients receiving placebo (p < or = 0.033). Improvements from baseline in AQLQ(S) overall and domain scores, daily asthma symptoms scores, percentage of symptom-free days, percentage of rescue medication-free days, and percentage of asthma control days were significantly greater in patients receiving budesonide/formoterol pMDI versus formoterol DPI (p < or = 0.042). Patients receiving budesonide/formoterol pMDI reported significantly greater PSAM scores than did patients in all other treatment arms (p < or = 0.004). Study limitations may include the fact that the formoterol-alone arm used a different device and formulation than the other active arms as well as the absence of a treatment arm with budesonide and formoterol administered concomitantly in separate inhalers. In addition, these results may not be generalized to all patients with asthma, as this analysis included only patients aged > or = 18 years.. Patients receiving treatment with budesonide/formoterol pMDI experienced significantly greater improvements from baseline in asthma-related quality of life, quality of sleep, and asthma control and greater satisfaction with treatment than patients receiving placebo. The combination of budesonide and formoterol in one pMDI is beneficial in improving how a patient feels and functions as a result of treatment.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Health Surveys; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Pressure; Quality of Life; Surveys and Questionnaires; Time Factors; Treatment Outcome

To evaluate the efficacy of 3 commonly used protocols for management of acute exacerbation of asthma in children.. Totally 113 asthmatic children were randomized into 3 groups. In group A (53 cases), the children were treated with inhalation of nebulized budesonide suspension plus salbutamol and ipratropium bromide twice daily for 5 days; in group B (41 cases), budesonide plus salbutamol and ipratropium aerosol was administered, and in group C (29 cases), dexathmisone plus aminophylline injection was given once daily for 5 days. All the children received basic treatment with fluid infusion, antibiotics or/and anti-virus medications.. The children in both groups A and C showed effectively controlled asthma attack, with significant differences in the therapeutic effects (P>0.05). In contrast, only a few children showed improvement in group B, suggesting the ineffectiveness of the treatment.. Nebulized medicine is one of the best means for management of acute asthma exacerbation in children, and inhalation of budesonide suspension plus salbutamol and ipratropium bromide can effectively relieve the asthmatic symptoms in these children with good compliance and convenient administration.

Topics: Acute Disease; Adolescent; Aerosols; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Ipratropium; Male; Treatment Outcome

Inhaled corticosteroids (ICS) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early. Whether treatment should be started with a high or low dose remains controversial. We investigated the importance of disease duration on the response to the starting dose of the ICS, budesonide, in asthma patients not previously treated with ICS.. Forty patients with newly detected asthma (symptoms for <12 months) and 41 patients with established asthma (mean duration 5.2 years, range 2-11) were randomized (double-blind, parallel-group) to treatment with budesonide Turbuhaler 100 or 400microg twice daily or placebo for 12 weeks.. For morning peak expiratory flow (mPEF), all four budesonide treatments resulted in statistically significant improvements from baseline and, after 12 weeks, the changes in all four groups were statistically significantly greater than placebo. In patients receiving early treatment, no significant differences were seen between budesonide doses. In patients with established symptoms, 800 mg/day [corrected] improved mPEF significantly more than 200 mg/day [corrected] The 200 mg/day [corrected] dose in the early treatment group improved mPEF significantly more than in the delayed treatment group. Changes in forced expiratory volume in 1s (FEV(1)), the concentration of inhaled histamine causing a 20% drop in FEV(1), and use of as-needed medication behaved in very similar ways to mPEF. Asthma symptoms were reduced in all budesonide groups without a difference between doses.. In patients with newly detected asthma treated early the initial ICS dose is not important. In contrast, in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a low dose.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control.. The open-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids.. Patients were randomized to double-blind treatment with budesonide, 200 mug (those aged < 11 years) or 400 mug once daily, or placebo plus the usual asthma therapy for 3 years, after which all patients received 2 years of open-label treatment with budesonide once daily.. During the full 5-year study period, postbronchodilator FEV(1) percent predicted decreased, irrespective of randomized treatment during the double-blind phase, by an average of 2.22% (SE, 0.15%). However, patients with inhaled budesonide in the double-blind phase had a significantly lower risk (odds ratio, 0.61; P < .001) of a severe asthma-related event during the full 5-year study period than those in the reference group. Moreover, patients in the reference group used more additional asthma medications during both the open-label and double-blind phases.. In mild persistent asthma early intervention with inhaled budesonide was associated with improved asthma control and less additional asthma medication use.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Placebos; Treatment Outcome

The dry powder inhaler (DPI) device for budesonide inhalation powder 200 microg (DPI-A) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 microg and 180 microg; DPI-B).. Two multicenter, parallel-group, double-blind, randomized, 12-week studies compared the efficacy and safety of budesonide delivered via each DPI versus placebo, and the systemic exposure of budesonide from each device.. Asthmatic adults with mild-to-moderate asthma (N = 621) and patients 6-17 years with mild asthma (N = 516) received budesonide DPI-B 360 microg or DPI-A 400 microg twice-daily (total daily dose 720 microg or 800 microg), budesonide DPI-B 180 microg or DPI-A 200 microg once daily (total daily dose 180 microg or 200 microg), or matching placebo. Change in forced expiratory volume in 1 second (FEV(1)) and secondary variables (asthma symptoms, beta(2)-adrenergic agonist use, peak expiratory flow [PEF], and withdrawals due to worsening asthma) versus placebo were measured.. In both studies, FEV(1) significantly (p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI-B 180 mug in adults. In the adult study, significantly (p < 0.05) greater improvements in all secondary variables occurred with all active treatments versus placebo. In the pediatric/adolescent study, improvements in AM/PM PEF were significantly (p or= 6 years with very mild asthma and adolescents and adults with mild-to-moderate asthma. The study is limited by the evaluation of only two doses for each product in both studies. Additionally, the studies were not designed to test equivalence or noninferiority between the active products. Pharmacokinetic characterization was limited because of the small sample sizes.

Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Analysis of Variance; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Male; Metered Dose Inhalers; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Sex Factors; Treatment Outcome

To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI-A 200 microg) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI-B). Budesonide DPI-B is available in two strengths (90 microg, 180 microg).. To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI-A and DPI-B and test for systemic absorption bioequivalence.. Adults (n = 37) with asthma as defined by the American Thoracic Society were randomized in an open-label, crossover, single-center, single-dose study to budesonide DPI-A 200 microg x 4 inhalations, budesonide DPI-B 180 microg x 4 inhalations, or budesonide DPI-B 90 microg x 8 inhalations, on 3 days, each separated by a washout period of >or= 5 days. Plasma samples were collected immediately before and up to 12 h after dosing. Primary pharmacokinetic variables were area under the drug plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) and maximum plasma concentration (C(max)); plasma concentration at 12 h (C(12h)) and time to maximum plasma concentration (T(max)) were secondary variables. Treatments were considered bioequivalent if the 90% confidence intervals (CIs) for their AUC(0-infinity) and C(max) ratios fell between 80 and 125%. Adverse events were collected.. The 90% CIs for the ratios of AUC(0-infinity) and C(max) for budesonide DPI-A 200 microg and DPI-B 180 microg and for both budesonide DPI-B strengths fell between 80% and 125% (AUC(0-infinity): budesonide DPI-B 180 microg x 4/DPI-A 200 microg x 4: 96.3% [90% CI: 90.9, 102.1]; budesonide DPI-B 180 microg x 4/DPI-B 90 microg x 8: 92.2% [90% CI: 87.0, 97.7]; C(max): (budesonide DPI-B 180 microg x 4/DPI-A 200 microg x 4: 100.4% [95% CI: 92.1, 109.4]; budesonide DPI-B 180 microg x 4/DPI-B 90 microg x 8: 94.4% [90% CI: 86.6, 102.9]). No differences in C(12h) and T(max) were found between treatments. All treatments were well tolerated.. Budesonide DPI-A 200 mug and DPI-B 180 mug have systemic absorption bioequivalence, and DPI-B 90 microg and 180 microg are dose-strength equivalent when administered at the same dose. These results may not be generalized to all patients with asthma, as this analysis included only patients with mild-to-moderate asthma aged >or= 19 years.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Confidence Intervals; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Airway responsiveness is a prognostic marker for asthma symptoms in later life.. To evaluate characteristics responsible for persistence of airway responsiveness in children with asthma.. A total of 1,041 children, initially aged 5-12 years, with mild to moderate persistent asthma enrolled in the Childhood Asthma Management Program (CAMP) were studied prospectively for 8.6 +/- 1.8 years with methacholine challenges yearly.. Least squares geometric mean models were fit to determine effects of sex and age on airway responsiveness (provocative concentration producing 20% decrease in FEV(1) [PC(20)]). Multiple linear regression analysis was performed to determine factors at baseline and over time, which were associated with PC(20) at end of follow-up. A total of 7,748 methacholine challenges were analyzed. PC(20) increased with age, with boys having greater increase after age 11 years than girls (P < 0.001). The divergence coincided with the mean age for Tanner stage 2. Postpubertal girls had greater airway responsiveness, even after adjustment for FEV(1) and other potential confounders. Although multivariable regression analyses noted a variety of factors that influenced airway responsivness in both sexes, a history of hay fever (beta= -0.30, P = 0.005), respiratory allergy (beta= -0.32, P = 0.006), or recent inhaled corticosteroid usage (beta= -0.18, P = 0.02) were associated with decrements in final log PC(20) only in girls.. Airway responsiveness (PC(20)) is more severe in the postpubertal female with asthma than in males. Although there are factors associated with airway responsiveness in both males and females, sex-specific factors may contribute to new insights into asthma pathogenesis.

Topics: Adolescent; Age Factors; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cohort Studies; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Least-Squares Analysis; Male; Methacholine Chloride; Nedocromil; Prognosis; Prospective Studies; Puberty; Sex Ratio; Vital Capacity

Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged > or = 18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 microg, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 microg x 1 inhalation, albuterol pMDI 90 microg x 2 inhalations (180 microg), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV(1)) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV(1) within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Salmeterol Xinafoate

High repeated doses of inhaled corticosteroids (ICSs) are recognized as having a more rapid improvement of outcomes than a single dose of ICS in severe acute asthma. However, to our knowledge, there has been no direct comparison of the early effects of single or repeated administration of the same total dosage of ICS in children with moderate to severe exacerbations of asthma.. To compare the efficacy of a single dose of 2000 microg of nebulized budesonide with 4 repeated doses of 500 microg of nebulized budesonide in 40 children with an acute asthma exacerbation.. Randomized, double-blind, parallel study that compared the efficacy of 2000 microg of nebulized budesonide, administered in a single dose, with repeated doses (4 doses of 500 microg each) during the first 90 minutes in 40 children (mean [SD] age, 10.7 [2.4] years) with an acute asthma exacerbation that required treatment with an oral corticosteroid. Forced expiratory volume in 1 second, asthma attack score, and oxygen saturation were evaluated at 20, 40, 60, 90, 120, 180, and 240 minutes after initial treatment. Oral corticosteroids were given to all patients at 90 minutes.. There were no significant differences in forced expiratory volume in 1 second (P = .54) at any times between the groups. Also, asthma scores and oxygen saturation were not different in either group within 90 minutes (P = .51 and P = .64, respectively) and thereafter (P = .35 and P = .87, respectively).. The use of a single dose of nebulized budesonide is as effective as repeated administration of the same total dosage during the first 90 minutes before giving oral corticosteroids in children with moderate to severe exacerbations of asthma.

Topics: Administration, Intranasal; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Nebulizers and Vaporizers; Oxygen; Statistics, Nonparametric; Vital Capacity

The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI.. We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI.. This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2).. There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated.. Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests

Inhaled glucocorticosteroids are usually administered in two equal daily doses. To simplify the method of treatment, once-daily administration has been used. However, little information regarding whether once-daily treatment can sufficiently control airway inflammation is available. We aimed to investigate whether once-daily administration of inhaled glucocorticosteroids can control airway inflammation.. Twenty-four well-controlled asthma patients were enrolled in a randomized crossover trial to compare the efficacies of once-daily and twice-daily administration of inhaled glucocorticosteroids. Initially, the patients were randomly assigned to receive either once-daily or twice-daily administration for 16 weeks. After an 8-week washout period, patients who originally received twice-daily administration were assigned to once-daily administration for 16 weeks and vice versa. We assessed the changes in the forced expiratory volume in 1s, morning and evening peak expiratory flows, asthma symptoms, health-related quality of life and fractional exhaled nitric oxide levels.. Patients with once-daily administration showed the same level of clinical control and lung functions as patients receiving twice-daily administration. There was no difference in the fractional exhaled nitric oxide levels between the beginning and end of the twice-daily treatment (35.69 and 33.23ppb, respectively). In contrast, the fractional exhaled nitric oxide level was significantly higher at the end of the once-daily treatment (33.87 and 39.38ppb, respectively, p< 0.001).. Although once-daily administration is sufficient for clinical control of asthma, it might not control airway inflammation sufficiently.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Breath Tests; Budesonide; Cross-Over Studies; Drug Administration Schedule; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Quality of Life

There have been no previous large, well-designed direct comparisons of the effects of fluticasone propionate (FP) and budesonide (BUD) on growth in children. This randomised, double-blind study compared the effects on growth of FP and BUD in children aged 6-9 years with persistent asthma. Following a 6-month run-in period (without inhaled corticosteroids), patients with normal growth velocity were randomised to 12 months' treatment with FP 100 micro g bd (n=114) or BUD 200 micro g bd (n=119). Growth velocity was determined by stadiometric height measurement. Lung function, asthma symptoms and use of relief medication were also assessed. Annualised mean growth velocity during run-in was comparable in the two groups (FP: 5.9 cm/yr; BUD: 6.0 cm/yr). During the treatment period, adjusted mean growth velocity was significantly higher in the FP than the BUD group (5.5 cm/yr vs 4.6 cm/yr; P<0.001). Asthma control improved similarly in both treatment groups. Bone mineral density and overnight urinary cortisol:creatinine ratios were similar in the two groups. Drug-related adverse events were reported among 3% of FP-treated children, compared with 2% for BUD. In conclusion, this study demonstrates that FP for childhood asthma has significantly less impact on childhood growth velocity than a therapeutically equivalent dose of BUD.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Fluticasone; Growth; Humans; Hydrocortisone; Male; Regression Analysis; Treatment Outcome

In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate; Treatment Outcome

Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma.. A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study.. Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels.. Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnenediones; Treatment Outcome; Vital Capacity

Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values.. Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment.. R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04).. This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy.

Topics: Acetates; Adolescent; Airway Resistance; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Maximal Midexpiratory Flow Rate; Plethysmography, Whole Body; Quinolines; Respiratory Function Tests; Sulfides

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

The National Heart, Lung, and Blood Institute Childhood Asthma Management Program was initiated in 1991 and is now the largest and most comprehensive study of long-term intervention with anti-inflammatory therapy in children with mild to moderate asthma. The purpose of this perspective is to review key findings of the study and lessons learned in conducting research in more than 1000 children with persistent asthma for more than 10 years. A key lesson was absence of a continued effect of inhaled corticosteroid on lung growth during long-term follow-up even as symptoms and airway responsiveness remained improved.

Topics: Anti-Inflammatory Agents; Asthma; Budesonide; Child; Clinical Trials as Topic; Humans; Lung; National Institutes of Health (U.S.); Nedocromil; United States

The use of combination inhaled budesonide and formoterol as maintenance and reliever therapy significantly improves the risk and the time to exacerbations in asthma.. To explore the mechanisms underlying the effect of the reliever dose on exacerbations by examining the effect of combination therapy on the allergen challenge model when given after allergen exposure.. In a randomized, double-blind crossover study, single doses of budesonide/formoterol (400/12 mug), formoterol (12 mug), budesonide (400 mug), or placebo were administered during the acute bronchoconstriction response (early airway response) immediately after allergen inhalation in 15 patients with mild asthma. Allergen-induced late airway response (LAR), sputum inflammatory markers, airway hyperresponsiveness, and exhaled nitric oxide were measured.. All active treatments significantly attenuated the LAR, with budesonide/formoterol significantly better than its monocomponents (maximum FEV(1) fall: placebo, [mean +/- SEM] 21.2% +/- 3.1%; budesonide/formoterol, 4.2% +/- 1.4%; formoterol, 7.5% +/- 1.7%; budesonide, 10.4% +/- 1.6%). Allergen-induced change in methacholine PC(20) was significantly attenuated by budesonide/formoterol, but not by its monocomponents. Sputum cell counts and exhaled nitric oxide increased significantly after all allergen challenges, with no significant attenuation by any of the treatments. Therapy with combination and formoterol alone, but not budesonide, significantly reduced the early airway response.. A single dose of budesonide/formoterol was superior to its monocomponents in attenuating the allergen-induced LAR and airway hyperresponsiveness. These effects may represent the contribution of the reliever dose to the budesonide/formoterol maintenance and reliever regimen.. The protective effect against allergic airway responses with a single reliever dose of budesonide/formoterol is predominantly related to greater functional antagonism of airway smooth muscles.

Topics: Administration, Inhalation; Adolescent; Adult; Allergens; Asthma; Bronchial Hyperreactivity; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Methacholine Chloride

Montelukast and ketotifen are oral anti-allergy medications in asthmatic children. This study investigates the modulation effect of montelukast and ketotifen on children with intermittent to mild persistent asthma as demonstrated by the levels of peak expiratory flow (PEF), asthma scores (AS), exhaled nitric oxide (eNO) and plasma stromal cell-derived factor-1 (SDF-1) concentration in a randomized, prospective study.. Fifty asthmatic children were enrolled and received 8 weeks of treatment with oral montelukast sodium 5mg chewable tablet administered once daily, or 1mg ketotifen, and were followed for a 4-week post-treatment washout period. ENO concentration, AS and PEF were measured before, 2, 4, 6 and 8 weeks after initial treatment, and 4 weeks after cessation of treatment.. Montelukast therapy was showed to improve AS, PEF and eNO within 2 weeks and remained the improvement during the treatment period. Montelukast also significantly decreased plasma SDF-1 levels after 8 weeks of treatment. In contrast, the ketotifen treatment revealed no significant effects in these clinical parameters until 4 and 6 weeks of the therapy, and did not suppress plasma SDF-1 levels after 8 weeks of treatment. To prove whether montelukast directly suppressed SDF-1 induction, we studied effects of montelukast on the LPS-induced SDF-1 expression and SDF-1-induced chemotaxis of monocytic (THP-1) cells. Montelukast, but not ketotifen, could suppress SDF-1 expression and its related chemotaxis on THP-1 monocytic cells.. Leukotriene receptor antagonist, such as montelukast, may be a better non-steroid anti-inflammatory drug for mild childhood asthma in preventing airway inflammation.

Topics: Acetates; Administration, Oral; Adolescent; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Budesonide; Calcium; Cell Line; Cell Movement; Chemokine CXCL12; Chemokines, CXC; Chemotaxis; Child; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Exhalation; Female; Flavonoids; Humans; Ketotifen; Male; Monocytes; Nitric Oxide; Peak Expiratory Flow Rate; Prospective Studies; Quinolines; Sulfides

This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 microg/day) received budesonide/formoterol 160/4.5 microg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 microg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 microg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p=0.0034 and p=0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49-0.76, p<0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57-0.90, p=0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Secondary Prevention; Treatment Outcome

It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma.. The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children.. Forty-eight steroid-naïve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily.. All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels.. This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.

Topics: Acetates; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Nitric Oxide; Quinolines; Sulfides

In some patients, asthma control is improved by combining inhaled corticosteroids with long-acting beta(2)-agonists. However, fluctuating asthma control and exacerbations can still occur. The STAY study evaluated whether, in patients with moderate to severe asthma, replacing a short-acting beta(2)-agonist reliever with the combination of budesonide/formoterol as reliever would both provide rapid symptom relief and reduce asthma exacerbations. The study evaluated 2760 patients with asthma (4-80 years) randomized to budesonide 400 microg twice daily (bid) and terbutaline as reliever, budesonide/formoterol 100/6 microg bid and terbutaline as reliever, or budesonide/formoterol 100/6 microg bid both as maintenance and reliever. Children (age 4-11 years) used a once-daily maintenance dose. Budesonide/formoterol as maintenance and reliever significantly reduced severe exacerbation risk by 45% to 47% compared with the other 2 treatments and improved symptoms, awakenings, and lung function. The benefit was seen in patients of all ages. Subsequent studies have revealed that this beneficial effect of budesonide/formoterol as maintenance and reliever requires both components of the combination.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans

Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids. This study investigates the relationship between the clinical effect seen in response to additional treatment and the effect on airway inflammatory indices. Seventy-five adult asthmatic patients, incompletely controlled on 800 mcg budesonide/day, were randomised following a 4 week run-in period, to a double-blind, multi-centre controlled clinical trial of doubling inhaled corticosteroid (budesonide 1600 mcg/day) or adding 10mg montelukast for 12 weeks. Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages, leukotrienes C4, D4 and E4, IL-8, Eosinophil Cationic Protein (ECP) and histamine. Sputum evidence of inflammation (2.0% eosinophils) was seen in only 29% of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group. There were significant improvements in am PEF (montelukast: 31.7 L/min, budesonide: 32.3 L/min) and quality of life with both treatments. We conclude that while both treatments showed similar improvements in lung function and quality of life, there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Double-Blind Method; Female; Humans; Male; Middle Aged; Quinolines; Sputum; Sulfides; Treatment Outcome

To compare effectiveness of two combinations of domestic drugs in the form of dry powder for inhalation-biasten containing budesonide plus salbutamol hemisuccinate and benacort (budesonide) plus salben (salbutamol) in correction of disorders of the blood oxidant-antioxidant system (OAS) in patients with moderate bronchial asthma (BA).. A total of 46 patients with uncontrollable BA of moderate severity (16 males and 30 females) entered an open trial where they were randomized into two groups. Group 1 (n=25) inhaled biasten (2 inhalations 2 times a day), group 2 (n=21) received equivalent doses of benacort and salben for 12 weeks. The following parameters were assessed: a clinical response, peakflowmetry, flow-volume curve, daily need in beta2-agonists, OAS by intensity of methemoglobin (MET) spectra, free radicals (FR), catalase, ceruloplasmin, transferrin, superoxidedismutase (SOD).. Biasten treatment for 12 weeks brought about a good control over BA symptoms in 72% patients, satisfactory--in 24%, no control--in one patient. In combined therapy with benacort and salben the respective percentage was 71.4 and 19.1, failure--in 2 patients. A clinical response in both groups differed insignificantly. The responders showed significant correction of OAS unbalance (but not of OAS erythrocytes), reduction of MET and FR concentrations, elevation of SOD and catalase. Anti-oxidant properties of blood plasm did not change significantly in response to the studied drugs administration.. Both biasten and benacort in combination with salben provide BA control, reduce severity of free radical oxidation disorders.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Antioxidants; Asthma; Budesonide; Drug Combinations; Female; Free Radicals; Humans; Lipid Peroxides; Male; Methemoglobin; Middle Aged; Nebulizers and Vaporizers; Oxidative Stress; Powders; Treatment Outcome

The effect of inhaled steroids on oxidative stress in asthmatics is unclear. The levels of lipid peroxides in the serum of asthmatic patients, whose symptoms were controlled with inhaled corticosteroids and long-acting beta(2)-agonists, were measured in this study.. Twenty asthmatic patients and 17 matched, healthy controls were recruited. Oxidative stress levels were quantified by measuring thiobarbituric acid reactive substances.. After 3 months of treatment, the mean lipid peroxide concentrations were significantly higher in asthmatic patients than in the healthy controls (4.2 +/- 0.13 micromol/mL vs. 3.6 +/- 0.07 micromol/mL, respectively).. The level of lipid peroxides is higher in patients with asthma than in healthy controls, even when the asthma is well controlled after 3 months of treatment. A longer period of therapy may be required before lipid peroxidation normalizes.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Lipid Peroxides; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Salmeterol Xinafoate; Thiobarbituric Acid Reactive Substances

The role of neutrophils in exacerbations of asthma is poorly understood. We examined the effect of withdrawal of inhaled corticosteroids on sputum inflammatory indexes in a double-blind study in patients with moderate, stable asthma.. Following a 2-week run in period, 24 subjects were randomized to receive either budesonide (400 microg bid) or placebo, and the study was continued for another 10 weeks.. Loss of asthma control developed in 8 of 12 patients over the 10-week period of steroid withdrawal, whereas only 1 of 10 patients with budesonide treatment had exacerbations. Those with an exacerbation had increased sputum interleukin (IL)-8 (p < 0.0001) and increased sputum neutrophil numbers (p < 0.0001) compared to those without an exacerbation. The significant elevation in sputum IL-8 and neutrophil counts initially occurred 2 weeks prior to an exacerbation. Sputum neutrophilia correlated positively with changes in IL-8 levels (r(2) = 0.76, p = 0.01).. Rapid withdrawal of inhaled corticosteroids results in an exacerbation of asthma that is preceded by an increase in sputum neutrophils and IL-8 concentrations, in contrast to an increase in eosinophils reported in previous studies in which inhaled steroids are slowly tapered.

Topics: Adolescent; Adult; Asthma; Budesonide; Cell Count; Double-Blind Method; Eosinophils; Female; Glucocorticoids; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Sputum

Improving patients' health-related quality of life (HRQoL) is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP) and an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide (FOR/BUD) where treatment is adjusted based on symptoms [SAM40056].. A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS) plus a long-acting beta2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 mug BID or 2 inhalations of FOR/BUD 6/200 mug BID during Weeks 1-4. For Weeks 5-52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP.. The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034) and the annual exacerbation rate was significantly lower (47%; p = 0.008) with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ) at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52). However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively). The minimally important difference of >/= 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049); a trend for this difference remained at Week 52 (71% vs 65%) (p = 0.205).. In this population of patients with persistent asthma, stable-dose SAL/FP resulted in significantly greater increases in symptom-free days, a reduction in exacerbation rates, and provided greater HRQoL benefits compared with FOR/BUD AMD.. Clinical Trials registration number NCT00479739.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; Treatment Outcome

The aim of the study was to investigate the efficacy and safety of ciclesonide compared with budesonide in adolescents with severe asthma.. In this randomized, double-blind, double-dummy, parallel-group study, patients aged 12-17 years with severe asthma were treated with budesonide 400 microg once daily (QD) in a 2-week run-in period. At randomization, eligible patients were assigned 2:1 to ciclesonide 320 microg QD (ex-actuator) or budesonide 800 microg QD (metered dose), respectively, in the evening. Forced expiratory volume in 1s (FEV(1)) was the primary variable. Patients recorded asthma symptom score and rescue medication use in diaries. Safety assessments included adverse events (AEs) and 24-h urine cortisol.. Four hundred and three patients were randomized. Ciclesonide 320 microg QD and budesonide 800 microg QD significantly increased FEV(1) (least-squares mean: 505 and 536 mL, respectively; both p<0.0001 versus baseline) in the intention-to-treat (ITT) population. Lower limits of the 95% confidence intervals (ITT: -138 mL; per-protocol: -122 mL) were above the non-inferiority limit (-150 mL). Median percentage of days without asthma symptoms and without rescue medication use was 84% with ciclesonide and 85% with budesonide. AEs were unremarkable, with no cases of confirmed candidiasis. Median creatinine-adjusted urine cortisol significantly decreased with budesonide treatment (15.9-13.7 nmol cortisol/mmol creatinine; p=0.0086 versus baseline), but not with ciclesonide (p=0.1125).. Ciclesonide 320 microg QD showed similar efficacy to budesonide 800 microg QD in adolescents with severe asthma. Ciclesonide was well tolerated and, unlike budesonide, had no effect on urine cortisol levels.. EudraCT No.: 2004-001233-41.

Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Pregnenediones; Quality of Life; Treatment Outcome; Vital Capacity

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.

Topics: Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Humans; Male; Pregnenediones; Respiratory Function Tests; Treatment Outcome

Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma.. To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1).. Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study.. Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents.. Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.

Topics: Acetates; Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; India; Male; Quinolines; Sulfides

Inhaled corticosteroids and anti-leukotriene agents are widely used in the treatment of pediatric asthma. Although data on the effect of corticosteroids on growth are available, there are few such data on anti-leukotriene agents. The aim of this study was to assess the influence of montelukast on short-term lower leg growth rate (LLGR) in prepubertal children with asthma.. Forty-two boys (6- to 12-year old) and 29 girls (6- to 11-year old) with mild asthma were randomized to 1 of 2 crossover arms, with two treatment sequences per arm: montelukast 5 mg once daily/placebo or inhaled dry powder budesonide 200 microg twice daily/placebo. Budesonide was used as a positive control to ensure that the method was sensitive enough to detect a suppression of LLGR. The 3-week double-blind treatment period was followed by a 3-week washout. Primary outcome was LLGR over the 3-week treatment, measured by knemometry.. Ninety-four percent of patients completed the study. Mean LLGR was similar between patients receiving montelukast and placebo treatments: mean difference, -0.02 mm/week [95% confidence interval -0.14, 0.11]. Mean LLGR in patients receiving budesonide was significantly less than for those receiving placebo (difference of -0.16 mm/week [-0.25, -0.06], P = 0.002). Mean LLGR was similar for patients taking placebo in the two arms (0.43 and 0.44 mm/week).. Montelukast 5 mg did not significantly affect short-term LLGR in prepubertal children.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Body Height; Budesonide; Child; Cyclopropanes; Double-Blind Method; Female; Humans; Leg; Male; Quinolines; Sulfides; Treatment Outcome

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific-allergen immunotherapy, the efficacy of long-term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel-group, controlled study. Children with asthma aged 4-16 yr, sensitive to house dust mite (HDM) were followed up for a run-in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom-medication scores and lung function tests every 3 months, as well as skin-prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within-group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM-allergic children with asthma.

Topics: Administration, Inhalation; Administration, Sublingual; Adolescent; Adrenal Cortex Hormones; Animals; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Budesonide; Child; Child, Preschool; Combined Modality Therapy; Desensitization, Immunologic; Female; Humans; Hypersensitivity; Immunoglobulin E; Infant; Male; Prospective Studies; Pyroglyphidae; Respiratory Function Tests; Skin Tests; Time Factors; Treatment Outcome

Nebulized budesonide inhalation suspension (BIS) is approved in the United States for children with asthma aged 1 to 8 years.. The primary objective of this study was to compare the efficacy of BIS 0.5 mg QD and 2.0 mg BID in terms of the mean change from baseline to end of treatment in predose forced expiratory volume in 1 second (FEV1).. In this 12-week, partially blinded, randomized study, subjects aged >or=12 years with moderate to severe persistent asthma previously receiving inhaled corticosteroids (ICSs) by dry powder inhaler (DPI) or metered-dose inhaler (MDI) continued therapy during a 2- to 3-week run-in period and then switched to BIS 0.5 mg QD, 1.0 mg QD, 1.0 mg BID, or 2.0 mg BID, or budesonide DPI 400 microg BID (active reference arm). Besides FEV1 (the primary variable), other outcome variables included changes in forced vital capacity (FVC) from baseline to weeks 4, 8, and 12 and to the average over the treatment period; as well as changes from baseline to the end of treatment in diary-collected daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings due to asthma, morning and evening peak expiratory flow (PEF), percentages of symptom-free and medication-free periods, and the incidence of predefined asthma events. Adverse events were recorded by subjects. Steady-state pharmacokinetics of budesonide were assessed in all treatment arms. Efficacy analyses included data in a modified intent-to-treat approach. Differences in the change from baseline to end of treatment in FEV1 were assessed using analysis of covariance (ANCOVA). For secondary variables, changes from baseline to each visit or to the treatmentperiod average were compared among groups using an ANCOVA model. P or=65 years. There was no significant difference in mean change in predose FEV1 between BIS 0.5 mg QD and BIS 2.0 mg BID (0.02 vs 0.01 L). On average, mean values for the BIS dosage groups did not indicate any deterioration from baseline to the treatment period for variables associated with asthma control such as FEV1, FVC, daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings, morning and evening PEF, percentages of symptom-free and rescue medication-free periods, and predefined asthma events. The BIS 1.0-mg BID treatment appeared to be closest to budesonide DPI in plasma budesonide concentrations and improvement in predose FEV1 (0.08 vs 0.12 L). All treatments were well tolerated.. In this study, no difference in efficacy between BIS 2.0 mg BID and 0.5 mg QD was found in adolescents and adults with persistent asthma when transitioned from ICSs delivered with a DPI or MDI. Subjects taking all BIS dosages experienced similar responses for variables associated with asthma control.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Powders; Severity of Illness Index; Sex Factors; Single-Blind Method; Time Factors; Treatment Outcome

The addition of the long-acting beta(2)-adrenergic agonist formoterol to low- to moderate-dose budesonide has shown clinical efficacy in patients with persistent asthma. Combination therapy with budesonide/formoterol in 1 pressurized metered-dose inhaler (pMDI) has been found to have greater efficacy than its monocomponents in patients with moderate to severe persistent asthma, but it has not been assessed in patients with mild to moderate persistent asthma.. The aim of this study was to compare the efficacy and tolerability of budesonide and formoterol delivered via 1 pMDI (budesonide/formoterol pMDI), budesonide pMDI, formoterol dry powder inhaler (DPI), and placebo.. This 12-week, multicenter, double-blind, randomized, placebo-controlled, double-dummy study was conducted at 56 centers across the United States. Patients aged > or =12 years with mild to moderate persistent asthma treated with inhaled corticosteroids (ICSs) for > or =4 weeks before screening and who had a forced expiratory volume in 1 second (FEV(1)) of > or =60% to < or =90% of predicted normal at screening were eligible. After 2 weeks (current asthma therapy discontinued), patients received twice-daily budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), budesonide pMDI 80 microg x 2 inhalations (160 microg), formoterol DPI 4.5 microg x 2 inhalations (9 microg), or placebo. The coprimary efficacy variables were changes from baseline in morning predose FEV(1) and 12-hour mean FEV(1) (from serial spirometry) after administration of the morning dose of study medication. Tolerability was assessed based on adverse events (AEs); routine laboratory assessments; electrocardiography; 24-hour Holter monitor assessments; and physical examinations, including vital signs (eg, systolic and diastolic blood pressure and heart rate). AEs were recorded manually by the patient in paper notebooks and reviewed at each clinic visit by the investigator and during a final follow-up phone call.. A total of 480 patients were randomized (299 females, 181 males; mean age, 36 years; mean FEV(1), 2.4 L; budesonide/formoterol pMDI, 123 patients; budesonide pMDI, 121; formoterol DPI, 114; placebo, 122). At end of treatment, the mean increases from baseline in predose FEV(1) were greater with budesonide/formoterol pMDI versus budesonide pMDI, formoterol DPI, and placebo (0.37 vs 0.23, 0.17, and 0.03 L, respectively; all, P<0.005). 0.005). After administration of the first dose and at weeks 2 and 12, mean increases in 12-hour mean FEV(1) were significantly greater with budesonide/formoterol pMDI (0.41, 0.47, and 0.50 L, respectively) versus budesonide pMDI (0.17, 0.30, and 0.32 L) and placebo (0.15, 0.12, and 0.12 L) (all, P < 0.001). Fewer patients receiving budesonide/formoterol pMDI met criteria for (18.7%; P < 0.001) or withdrew because of (7.3%; P < or = 0.010) worsening asthma versus formoterol DPI (42.1% and 18.4%, respectively) and placebo (56.6% and 32.8%); results were similar between budesonide pMDI (21.5% and 6.6%, respectively) and budesonide/formoterol pMDI. Three patients experienced serious AEs; none was considered related to study medication. The proportions of withdrawals due to worsening asthma were not significantly different between the budesonide/formoterol pMDI and budesonide pMDI groups.. In this population of adults and adolescents with mild to moderate persistent asthma previously treated with ICSs, twice-daily budesonide/formoterol pMDI was associated with significantly increased pulmonary function versus its monocomponents. All study drugs were generally well tolerated.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Patient Compliance

To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation.. Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inhalation, FEV(1) was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits.. The mean difference in FEV(1) prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36-75) and 29% (IQR 2-44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007.. The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Treatment Outcome

Budesonide/formoterol (Symbicort) Maintenance and Reliever Therapy (SMART) is an effective asthma-management approach that treats symptoms with rapid increases in budesonide/formoterol. The cost-effectiveness of SMART vs higher fixed-dose budesonide/formoterol or salmeterol/fluticasone is unknown.. This 6-month, double-blind study randomized patients with asthma uncontrolled by inhaled corticosteroids alone (n = 3335; age > or =12 years) to budesonide/formoterol 160/4.5 microg b.i.d. plus additional doses as needed (SMART), budesonide/formoterol 320/9 microg b.i.d. plus as-needed terbutaline, or salmeterol/fluticasone 50/250 microg b.i.d. plus as-needed terbutaline. Economic analysis, assuming health care and societal perspectives, applied 2004 UK and Australian unit costs to pooled resource-use data. The effectiveness variable was the rate of severe exacerbations/patient/6 months.. Patients treated using the SMART approach experienced fewer severe exacerbations than fixed-dose budesonide/formoterol and salmeterol/fluticasone patients (0.12 vs 0.16 and 0.19 events/patient/6 months, respectively; P < or = 0.0048). Budesonide/formoterol (Symbicort) Maintenance and Reliever Therapy provided similar improvements in other markers of asthma control at a lower overall daily inhaled corticosteroid dose compared with fixed-dose treatment. Study drug costs accounted for a majority of both direct costs (DC; 78-87%) and total costs (TC; 50-63%) for all treatments, and were significantly lower in the SMART group compared with the fixed-dose groups (P < or = 0.0014). Direct and TC per patient/6 months were lower for SMART vs salmeterol/fluticasone (DC:-AUS$154, P < 0.0001; TC:-AUS$163, P = 0.0036;-87 pound sterling, P = 0.0026) and vs budesonide/formoterol using UK costs (DC:-73 pounds sterling, P < 0.0001; TC:- 91 pounds sterling, P = 0.0014). Costs tended to be lower for SMART vs budesonide/formoterol using Australian costs (DC:-AUS$35, P = 0.16; TC:-AUS$70, P = 0.20). Results were stable under sensitivity testing. Indirect resource use and cost were not significantly different between groups.. Compared with higher fixed-dose budesonide/formoterol and salmeterol/fluticasone, SMART reduces the incidence of severe exacerbations at a lower or similar overall cost and can be considered a cost-effective treatment regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Australia; Bronchodilator Agents; Budesonide; Child; Cost of Illness; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Costs; Drug Therapy, Combination; Economics, Pharmaceutical; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; United Kingdom

Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler).. This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged > or = 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50-90% predicted normal and were inadequately controlled on inhaled corticosteroids (500-1600 microg/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 microg, budesonide/formoterol DPI 160/4.5 microg or budesonide/formoterol pMDI 160/4.5 microg. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF).. In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: -10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated.. Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Powders; Quality of Life; Treatment Outcome

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA).. Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed, for 6 months.. Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated.. In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Azides; Budesonide; Child; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Hospitalization; Humans; Lung; Male; Middle Aged; Proportional Hazards Models; Respiratory Function Tests; Serotonin; Treatment Outcome

The traditional chlorofluorocarbon (CFC) propellants used in pressurized metered-dose inhalers (pMDIs) have unacceptable environmental effects and are being replaced by alternatives such as hydrofluoroalkanes (HFAs). However, there is a need to ensure that pMDIs with these novel propellants are as effective and safe as their older counterparts.. Single-dose pharmacokinetic and multiple high-dose Phase I studies in healthy volunteers and randomized, controlled 12-week Phase III clinical trials in children, adolescents and adults with mild-to-moderate asthma have been performed to compare the efficacy and safety of HFA-based budesonide inhaler therapy with the traditional CFC-based pMDI.. The pharmacokinetic study in 40 persons showed comparable characteristics of CFC and HFApMDIs, with good dose-proportionality, at doses of 400, 800 and 1,600 microg. The high-dosage (1,600 microg/day) study in 48 subjects showed both inhaler types to be similar in terms of effects on hypothalamic-pituitary-adrenal axis function over 4 weeks. The pediatric clinical study involved 159 children and showed noninferiority of the HFA pMDI in terms of 12-week change in forced expiratory volume in 1 sec, other spirometric parameters and symptomatic measures. The adolescent/adult study in 321 subjects also showed similarity between the two formulations, in terms of 12-week primary endpoint (changes in morning peak expiratory flow rates) and other lung function and symptom measures. Both formulations were well-tolerated, with no safety issues being identified for the novel HFA inhaler in any study.. Budesonide HFA pMDI is pharmacokinetically and clinically comparable to the traditional CFC-based inhaler, with similar safety profile.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Chlorofluorocarbons; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hypothalamo-Hypophyseal System; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Therapeutic Equivalency

Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations.. To determine whether variation in the low-affinity IgE receptor gene, FCER2, is associated with severe exacerbations defined as emergency department visits and/or hospitalizations in patients with asthma on ICSs.. We resequenced, then genotyped 10 FCER2 single nucleotide polymorphisms (SNPs) in 311 children randomized to inhaled budesonide as part of the Childhood Asthma Management Program. We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial. We also evaluated differences in cellular expression of the novel FCER2 SNP, T2206C.. In white subjects, 3 FCER2 SNPs were significantly associated (P < .05) with elevated 4-year IgE level; each was also associated with increased severe exacerbations. Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children (hazard ratio, 3.95; 95% CI, 1.64-9.51; and hazard ratio, 3.08; 95% CI, 1.00-9.47), despite ICS use. Interaction models supported a true gene-environment effect in white subjects (interaction P = .004). T2206C was also associated with decreased FCER2 expression (P = .02).. FCER2 predicts the likelihood of treatment protocol success in asthma. The associations of T2206C with IgE level, severe exacerbations, and FCER2 expression may provide a mechanistic basis for the observed findings.. Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Child; Female; Humans; Immunoglobulin E; Male; Polymorphism, Single Nucleotide; Receptors, IgE; Severity of Illness Index

Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed.. To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast.. After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments.. No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide.. Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast.. These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast.

Topics: Acetates; Administration, Inhalation; Age Factors; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cyclopropanes; Female; Humans; Infant; Infant, Newborn; Male; Quinolines; Sulfides; Treatment Outcome

The duration of bronchodilator action of the long-acting beta-agonist formoterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of formoterol, administered from the combination budesonide/formoterol (BUD/F) Turbuhaler significantly attenuates the circadian rhythm in airway tone over 24 h.. Twenty subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, placebo-controlled, cross-over study. Subjects inhaled, in random order, placebo or BUD/F (2x100/6 microg) administered in the evening (2000 h) on two separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h.. Compared with placebo, BUD/F significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.20L (0.04-0.35L). BUD/F attenuated the biphasic pattern of the circadian rhythm in airway tone.. The single evening administration of formoterol from the combination BUD/F inhaler resulted in a duration of bronchodilation of at least 24 h.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Chronotherapy; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Maximal Expiratory Flow Rate; Middle Aged; Treatment Outcome

Adjustable maintenance dosing with either budesonide/formoterol or budesonide was compared in asthma patients. This double-blind trial randomized 133 patients (mean forced expiratory volume in 1s 66% predicted) to receive 2 inhalations twice daily of budesonide/formoterol 160/4.5 microg (640/18 microg/day) or budesonide 320 microg (1280 microg/day) for 4 weeks. The study drug was adjusted in both groups according to symptoms to 2-4 inhalations daily during Weeks 5-8 and 1-4 inhalations daily during Weeks 9-20. Asthma was well controlled in both groups, with minimal levels of treatment failure (5 budesonide/formoterol vs. 2 budesonide patients; P=NS) and minimal use of reliever therapy. Clinically important improvements in health-related quality of life (HRQL) occurred in the physical functioning and emotional role functioning domains (both P<0.05) for the budesonide/formoterol group compared with budesonide. Physician and patient treatment satisfaction favored budesonide/formoterol (both P<0.05). Budesonide/formoterol patients used fewer daily inhalations of study drug (P=0.024). The median average daily inhaled corticosteroid dose during the study was 448 microg with budesonide/formoterol and 1152 microg with budesonide. Adjustable maintenance dosing with budesonide/formoterol and budesonide resulted in high levels of asthma control. Adjustable budesonide/formoterol treatment achieved greater HRQL benefits and patient satisfaction, with lower overall drug use.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Patient Satisfaction; Quality of Life

This study compared the efficacy and safety of budesonide/formoterol (Symbicort) Turbuhaler)) with salbutamol pressurized metered-dose inhaler (pMDI) with spacer for relief of acute bronchoconstriction in patients with asthma. In this randomized, double-blind, parallel-group study, patients (n = 104 allocated to treatment; n = 103 received treatment; mean age 45 years) seeking medical attention for acute asthma (mean FEV(1) 43% of predicted) received two doses repeated at t = -5 and 0 min of either budesonide/formoterol (320/9 microg, two inhalations) or salbutamol (100 microg x eight inhalations); total doses 1280/36 microg and 1600 microg, respectively. All patients received prednisolone 60 mg at 90 min and FEV(1) was assessed over 3h. FEV(1) 90 min after dosing (primary variable) increased compared with pre-dose FEV(1) by an average of 30% and 32% for budesonide/formoterol and salbutamol, respectively (P = 0.66), with similar increases at all timepoints from 3 to 180 min for both groups. Mean pulse rate over 3h was significantly higher in the salbutamol group versus the budesonide/formoterol group (92 vs. 88 bpm; P < 0.01). No treatment differences were seen for other vital signs, including ECG. High-dose budesonide/formoterol was effective and well tolerated for the treatment of acute asthma, with rapid onset of efficacy and a safety profile over 3h similar to high-dose salbutamol.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Electrocardiography; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests

In this economic evaluation, conducted alongside a randomized, double-blind clinical trial, economic data were collected from 339 patients with moderate-persistent asthma randomized to receive twice-daily, double-blind treatment with budesonide/formoterol 160/4.5 microg in a single inhaler (n=166) or fluticasone propionate 250 microg (n=173) for 12 weeks. The mean number of episode-free days (EFD) per patient was significantly greater in the budesonide/formoterol group than the fluticasone group (48.71 compared with 42.34, P=0.0185). Data on medication use, visits to healthcare professionals, and hospitalization were pooled across all six countries and combined with German and Dutch unit cost data to calculate total healthcare costs. Using German unit costs, budesonide/formoterol was associated with significantly lower total healthcare costs per patient over the 12-week period compared with fluticasone (euro 131 compared with euro 210, P=0.0043). Using Dutch unit costs, total healthcare costs were slightly numerically lower in the budesonide/formoterol group than the fluticasone group (euro 102 compared with euro 104), but the difference did not reach statistical significance. Budesonide/formoterol in a single inhaler is more effective than a higher microgram dose of fluticasone alone. It is cost-neutral and may provide cost-savings in some countries.

Topics: Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Health Care Costs; Humans; Middle Aged

Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children. Children with persistent moderate asthma (according to GINA criteria), 8 to 11 years old, were divided into 3 groups: morning training group (N = 23), afternoon training group (N = 23), and non-training group (N = 23). The program was based on twice a week 90-min sessions for 4 months. We measured the 9-min running distance, resting heart rate and abdominal muscle strength (sit-up number) before and after the training. All children took budesonide, 400 microg/day, and an on demand inhaled ss-agonist. The distance covered in 9 min increased (mean +/- SEM) from 1344 +/- 30 m by 248 +/- 30 m for the morning group, from 1327 +/- 30 m by 162 +/- 20 m for the afternoon group, and from 1310 +/- 20 m by 2 +/- 20 m for the control group (P < 0.05 for the comparison of morning and afternoon groups with the control group by ANOVA and P > 0.05 for morning with afternoon comparison). The reduction of resting heart rate from 83 +/- 1, 85 +/- 2 and 86 +/- 1 bpm was 5.1 +/- 0.8 bpm in the morning group, 4.4 +/- 0.8 bpm in the afternoon group, and -0.2 +/- 0.7 bpm in the control group (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). The number of sit-ups in the morning, afternoon and control groups increased from 22.0 +/- 1.7, 24.3 +/- 1.4 and 23 +/- 1.1 sit-ups by 9.8 +/- 0.9, 7.7 +/- 1.4, and 1.9 +/- 0.7 sit-ups, respectively (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children.

Topics: Abdominal Muscles; Albuterol; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Case-Control Studies; Child; Circadian Rhythm; Combined Modality Therapy; Exercise Therapy; Female; Heart Rate; Humans; Male; Prospective Studies; Respiratory Function Tests; Severity of Illness Index

The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids.. The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone.. Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR).. All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01).. Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Delayed-Action Preparations; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Patient Selection; Quinolines; Sulfides; Theophylline

The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma.. Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint.. In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups.. Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Vital Capacity

To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting beta2-agonist therapy.. In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 microg), were randomized to receive either budesonide/formoterol (320/9 microg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 microg]) or formoterol (9 microg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 microg]). The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured.. FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated.. Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting beta2-agonist.

Topics: Acute Disease; Adrenergic beta-Agonists; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Drug Resistance; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Lung; Respiratory Function Tests; Time Factors; Treatment Outcome

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.

Topics: Acetates; Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eosinophils; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Leukocyte Count; Lung Volume Measurements; Male; Methacholine Chloride; Middle Aged; Quinolines; Sputum; Sulfides

The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months.. 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months.. Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups.. Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cromolyn Sodium; Double-Blind Method; Female; Germany; Humans; Infant; Male; Nebulizers and Vaporizers; Treatment Outcome

To compare a novel asthma management strategy--budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief--with a higher dose of budesonide plus as-needed terbutaline.. This was a 6-month, randomized, double-blind, parallel-group study in patients with mild-to-moderate asthma (n = 697; mean age, 38 years [range, 11 to 79 years]; mean baseline FEV1, 75% of predicted; mean inhaled corticosteroid [ICS] dosage, 348 microg/d). Following a 2-week run-in period, all patients received two blinded, dry powder inhalers, one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms. Patients were randomized to receive either budesonide/formoterol (80 microg/4.5 microg, two inhalations qd) for maintenance plus additional inhalations as needed for symptom relief, or budesonide (160 microg, two inhalations qd) for maintenance medication plus terbutaline (0.4 mg) as needed. The primary efficacy variable was morning peak expiratory flow (PEF).. Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide (increases of 34.5 L/min vs 9.5 L/min, respectively; p < 0.001). The risk of having a severe exacerbation (hospitalization/emergency department [ED] treatment, oral steroids for asthma, or a > or = 30% decrease from baseline in morning PEF on 2 consecutive days) was 54% lower with budesonide/formoterol vs budesonide (p = 0.0011). Budesonide/formoterol patients experienced 90% fewer hospitalizations/ED treatments due to asthma than budesonide patients (1 vs 10, respectively; p = 0.026). The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group (mean dose, 240 microg/d vs 320 microg/d, respectively) and with 77% fewer oral steroid treatment days vs budesonide (114 days vs 498 days, respectively). Both treatments were well tolerated.. Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders; Terbutaline

Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later.. To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo.. Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization.. Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment.. HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aerosol Propellants; Algorithms; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Budesonide; Cytokines; Double-Blind Method; Eosinophils; Female; Humans; Hydrocarbons, Fluorinated; Lymphocytes; Male; Powders; Sputum

Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Bronchi; Bronchoconstriction; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Histamine; Humans; Male

Inhaled corticosteroids are known to be effective in persistent asthma, but their long-term effect in mild persistent disease of recent onset, which is particularly relevant in children, requires clarification. The objective of this study was to determine the long-term efficacy of regular inhaled low-dose budesonide in children aged <11 yrs with mild persistent asthma with onset within 2 yrs of enrollment. Children aged 5-10 yrs formed part of the population of the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study, and they were randomized in a double-blind manner to treatment with once daily budesonide 200 microg or placebo via Turbuhaler in addition to usual clinical care and other asthma medication. The double-blind treatment phase continued for 3 yrs. Of the 1974 children, 1000 in the budesonide group and 974 in the placebo group, were analyzed for efficacy. Addition of once-daily budesonide to usual care was associated with a significant increase in the time to first severe asthma-related event (SARE) and significantly reduced risk of SARE over 3 yrs. The hazard ratio relative to usual care (placebo) was 0.60 (95% confidence interval: 0.40-0.90; p = 0.012), with a relative risk reduction of 40%. Children receiving budesonide also needed significantly less intervention with other inhaled corticosteroids (12.3% vs. 22.5% over 3 yrs; p < 0.01), with trends towards decreased usage of oral/systemic corticosteroids and inhaled short-acting beta2-agonists. Budesonide treatment also had a significant beneficial effect on lung function relative to placebo. In conclusion, early intervention adding once-daily budesonide to usual care in children with mild, persistent asthma of recent onset reduces the long-term risk and frequency of SAREs and improves lung function compared with usual care alone.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Pediatrics; Time Factors

The safety and tolerability of asthma medications are still a concern to many asthma patients receiving long-term treatment. Therefore, more safety data from long-term, controlled trials are needed. The aim of this study was to evaluate the safety and tolerability of long-term treatment with once-daily budesonide in children aged 5-10 yrs with mild persistent asthma of recent onset in the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study. Children aged 5-10 yrs with early asthma were randomized to double-blind treatment with budesonide 200 microg or placebo once daily via Turbuhaler in addition to usual asthma therapy, for 3 yrs. Adverse events were recorded from both spontaneous reports and responses to standard questions, and asthma-related events and asthma control were recorded between visits and subsequently graded by the blinded investigators. Of the study population of 1981 children (1004 budesonide and 977 usual care), 81% (812 of 1004) in the budesonide group and 82% (797 of 977) in the usual care group experienced a total of 6414 events listed by preferred term (3209 budesonide plus usual care and 3205 placebo plus usual care). The most commonly reported events included respiratory infection, pharyngitis, rhinitis, viral infection and bronchitis, and there were no clinically relevant differences in incidence between treatments. There were no reports of tuberculosis or aspergillosis, and no evidence of increased risk of systemic or ocular adverse events with budesonide relative to placebo. There were 106 serious adverse events in the budesonide group and 128 with usual care. The most frequent, aggravated asthma, was more common with usual care than with budesonide. There were no deaths among children participating in START. In conclusion, the addition of once-daily inhaled budesonide 200 microg via Turbuhaler to usual care is safe and well tolerated in children with recent-onset mild persistent asthma.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cough; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Pediatrics; Respiratory Tract Infections; Skin Diseases

The inhaled Steroid Treatment As Regular Therapy in early asthma (START) study has shown that early intervention with inhaled budesonide in mild persistent asthma improves clinical outcomes in both adults and children. The aim of this study was to estimate the incremental cost-effectiveness of early treatment with budesonide Turbuhaler in children aged 5-10 yr who participated in START. Direct and indirect costs associated with asthma were determined for 1974 children participating in the double-blind, 3-year part of the study. Randomization was to placebo or to budesonide 200 microg once daily in each case in addition to usual asthma care. Cost-effectiveness ratios were calculated from the healthcare payer's and societal perspectives (using US prices). The addition of once-daily budesonide therapy to usual asthma care was associated with 16 additional symptom-free days (SFDs) per child over the 3-yr period (p < 0.001), with a substantial reduction (50%) in the mean number of days spent in hospital, and with reduced frequency of emergency room visits and missed school and caregiver work days. From the healthcare payer's perspective (direct costs), the increase in mean direct cost over 3 yr with budesonide was 169 dollars, which translated into an incremental cost of early intervention with budesonide in children of 10.50 dollars (95% CI 1.20-33.30 dollars) per SFD gained. From the societal perspective, there was a cost reduction over 3 yr of 192 dollars with budesonide relative to placebo. From a societal perspective, budesonide was therefore dominant. In conclusion, early intervention with once-daily budesonide added to usual asthma care in children with mild persistent asthma is cost-saving from a societal perspective and is acceptably cost-effective when viewed from a healthcare payer perspective.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Pediatrics; Time Factors

The dose emitted from dry powder inhalers may be inhalation flow-dependent. Using an ex vivo method, the Electronic Lung, we have measured the aerodynamic characteristics of the emitted dose for both active constituents from Seretide Diskus (salmeterol xinafoate 50 mcg; fluticasone propionate 500 mcg) and Symbicort Turbuhaler (formoterol 6 mcg; budesonide 200 mcg). Electronic inhalation profiles were collected from 20 severe asthmatics (mean PEFR 53% predicted) when they inhaled using a placebo Seretide Diskus and a placebo Symbicort Turbuhaler. These were replayed in the Electronic Lung with the respective active inhaler in situ. Mean(S.D.) peak inhalation flow rates (PIFR) through the Diskus and Turbuhaler were 94.7(32.9) and 76.8(26.2) l min(-1), respectively. From the Electronic Lung the Diskus inhalation profiles provided a mean(S.D.) fine particle dose (FPD) for fluticasone propionate and salmeterol of 20.4(4.8) and 18.4(4.4)% labelled dose. For Turbuhaler inhalation profiles the FPD was 23.1(12.9) and 20.7(11.1)% labelled dose for budesonide and formoterol, respectively. The linear (p < 0.001) relationships between FPD against PIFR for budesonide and formoterol were 3 (p = 0.002) and 2.8 (p = 0.007) times steeper than fluticasone propionate and salmeterol, respectively. The results highlight a more significant effect of inspiratory flow on variable dosage emission when using the Symbicort Turbuhaler compared with the Seretide Diskus.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Severity of Illness Index

Budesonide/formoterol 160/4.5 microg, two inhalations bd, is an effective and well-tolerated maintenance therapy for patients not controlled on inhaled corticosteroids alone. The authors assessed the efficacy and safety of a higher dose of budesonide/formoterol in patients with persistent symptomatic asthma.. This was a 24-week, double-blind, double-dummy randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36 microg/day), was compared with corresponding doses of budesonide during weeks 1-12 and budesonide plus formoterol via separate inhalers during weeks 1-24. Efficacy was assessed during weeks 1-12; the primary variable was morning PEF. Safety was assessed over weeks 1-24.. Patients (n=456; aged 12-79 years) had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with budesonide/formoterol and budesonide plus formoterol, respectively, versus an increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide). Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus budesonide. Budesonide/formoterol and budesonide plus formoterol had similar efficacy. All treatments were well tolerated and the incidence of class-related adverse events was similarly low in all groups. Changes in serum potassium and plasma cortisol were comparable across treatments.. High-dose budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well tolerated in patients with persistent symptomatic asthma. The findings also support the safety of regular high-dose formoterol (36 microg/day).

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Follow-Up Studies; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Treatment Outcome

Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control.. To identify predictors of loss of control and the kinetics of symptoms, and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma.. In a single-blind study, the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20+/-2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days. The patients recorded symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured every 10 days. A loss of asthma control was defined as a worsening of the symptoms score of at least 20%, and either a decrease in FEV1 of at least 15% or a decrease in PC20 of at least fourfold.. Two patients had a respiratory infection and were withdrawn from the study. In eight patients, asthma became uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately reflected by a worsening of all parameters. The first parameter to change was the sputum eosinophil percentage (20 days before the loss of asthma control). Significant changes in exhaled nitric oxide, FEV1 and methacholine PC20 were observed only when the symptoms became uncontrolled. A high blood eosinophil count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control.. In patients whose asthma is controlled on inhaled corticosteroid, it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1% after the reduction of corticosteroids.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Middle Aged; Peak Expiratory Flow Rate; Single-Blind Method; Sputum; Substance Withdrawal Syndrome

This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids.. The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group.. The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated.. Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome

We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing.. We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study.. We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group (absolute difference, 1 percent; 95 percent confidence interval, -4.8 to 6.9 percent). Twenty-four percent of children in the budesonide group had persistent wheezing, as compared with 21 percent in the placebo group (hazard ratio, 1.22; 95 percent confidence interval, 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis. The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status. Height and bone mineral density were not affected by treatment.. Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. (ClinicalTrials.gov number, NCT00234390.).

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Disease Progression; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Prospective Studies; Respiratory Sounds; Risk Factors; Treatment Failure

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

To evaluate efficacy and cost-effectiveness of budesonide/formoterol (Symbicort) maintenance (one dose once or twice daily) plus additional doses as needed (Symbicort Maintenance And Reliever Therapy, SMART) compared with a higher fixed dose of budesonide/formoterol with formoterol as needed in patients with persistent asthma.. 6-month, open, randomised study of 465 patients either not well controlled on an inhaled corticosteroid (ICS), or well controlled on a combination of ICS and a long-acting beta(2)-agonist (LABA).. budesonide/formoterol 160/4.5 microg, one inhalation, once or twice daily maintenance plus additional doses as-needed (1 x SMART or 2 x SMART), or budesonide/formoterol 160/4.5 microg two inhalations twice daily plus formoterol 4.5 microg as needed (2 x 2 FIX + F). Children 6-11 years old used an 80/4.5 microg dose strength. Primary variables of efficacy were the changes in the Asthma Control Questionnaire (ACQ(5)) and morning peak expiratory flow (PEF).. Mean age of patients 40 years (range 6-82 years); 53% female. No differences between the groups were found in ACQ(5) scores or asthma exacerbation rates. Morning PEF was higher in the 2 x 2 FIX + F group vs. the 1 x SMART and 2 x SMART groups (differences 13 L/min and 9 L/min, respectively; p < 0.002). The 1 x SMART group showed a significant decrease in asthma controlled days compared with the two other groups. No difference was seen between the 2 x SMART group and the 2 x 2 FIX + F group. Treatment costs were significantly lower in the SMART groups compared with the 2 x 2 FIX + F group.. Compared with the 2 x 2 FIX + F treatment the use of budesonide/formoterol was 30-40% lower in the SMART groups while maintaining equal ACQ(5) scores. Daily asthma control improved equally with 2 x SMART compared to 2 x 2 FIX + F with a reduction in asthma medication cost. The one dose once daily maintenance treatment (1 x SMART) resulted in a low level of treatment failure (exacerbations) but led to more days with symptoms. Therefore, a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Health Care Costs; Humans; Quality of Life; Surveys and Questionnaires

Asthma care management programs may improve outcomes, but it is not clear which aspects of such management are responsible for the improvement. We performed a randomized controlled trial of a limited intervention (one visit with asthma self-management education and provision of inhaled budesonide) compared to this visit plus regular asthma care manager follow-up. Quality of life, symptom-free days, emergency hospital care, and beta-agonist dispensings did not differ between groups at 12 months. Patients who entered the study did receive significantly less beta-agonists in the follow-up year than patients who did not enter the study. These data suggest that the limited intervention in our setting improved outcomes but that regular care manager follow-up thereafter did not add significantly to this intervention.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Drug Utilization; Female; Glucocorticoids; Humans; Male; Middle Aged; Patient Care Management; Patient-Centered Care; Quality of Life; Risk; Socioeconomic Factors

Asthmatic patients lose lung function faster than normal subjects. The effectiveness of early intervention with inhaled corticosteroids on this decline in lung function is not established in recent-onset disease.. The Inhaled Steroid Treatment as Regular Therapy in Early Asthma study was a randomized, double-blind study in 7,165 patients (5 to 66 years old), with persistent asthma for < 2 years to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events and the decline in lung function. Patients received budesonide (200 mug qd for children < 11 years old and 400 mug qd for others) or placebo for 3 years in addition to usual asthma medications.. Treatment with budesonide significantly improved prebronchodilator and postbronchodilator FEV(1) percentage of predicted and reduced the mean declines from baseline for postbronchodilator FEV(1) at 1 year and 3 years: - 0.62% and - 1.79% for budesonide and - 2.11% and - 2.68% for placebo, respectively (p < 0.001). The decline was more marked for male patients, active smokers, and patients > 18 years old, and the smallest treatment effects were in adolescents.. Long-term, once-daily treatment with low-dose budesonide improved both prebronchodilator and postbronchodilator FEV(1) in patients with recent-onset, persistent asthma, and reduced the loss of lung function over time.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Treatment Outcome; Vital Capacity

Asthma, a chronic inflammatory condition of airways, responds to therapy with anti-inflammatory medications, for example, inhaled (ICS) and/or systemic (SS) corticosteroids. It is associated with impaired clearance of airway secretions. We studied effects of ICS and SS on mucociliary clearance (MC) in outpatient asthma through an in vivo, randomized, placebo-controlled single blind study with patients acting as their own control. Using a gamma camera and radiolabeled aerosol, we measured MC at baseline, after 4 days of nebulized treatment and after 5 days of oral prednisone. MC was expressed as percent of retained activity over time. Spirometry was performed before each MC study. Treatment with nebulized budesonide did not affect MC or forced expiratory volume at 1 sec (FEV1). Treatment with SS was associated with a significant improvement in MC at 24 h (baseline, 41 +/- 6; post-SS, 36 +/- 5; p = 0.04). Post hoc analysis revealed that MC changed only in those patients with significant changes in deposition (specific Central-to-Peripheral ratio C/P--baseline, 1.57 +/- 0.16; post-SS, 1.73 +/- 0.21; n = 6; p = 0.05), suggesting that the changes in MC were not directly related to therapy. In outpatient asthma, MC is unaffected by 4-5 days of anti-inflammatory therapy in spite of significant changes in FEV1.

Topics: Administration, Inhalation; Adult; Aged; Ambulatory Care; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Mucociliary Clearance; Prednisolone; Single-Blind Method

Budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (SMART) is an effective and well tolerated treatment option for patients with asthma. We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate (Seretide) plus salbutamol (albuterol) as needed (Seretide) Fixed Combination [SFC]).. A cost-effectiveness analysis was performed based on effectiveness and resource-utilisation data collected prospectively in a randomised, 12-month study performed in 2143 patients in 16 countries. Resource utilisation data were pooled and unit costs (euro, year 2003 values) from Italy, France, the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided.. Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1 second [FEV(1)] 73% predicted; mean inhaled corticosteroid [ICS] dose 884 microg/day) were randomised to SMART or SFC. The effectiveness measure used was the number of severe exacerbations per patient per year. Direct costs included medication use (budesonide/formoterol 160microg/4.5microg or salmeterol/fluticasone 50microg/100microg, 50microg/250microg or 50microg/500microg plus salbutamol) and nonmedication-related resource use, including days in hospital, emergency room visits, specialist or primary care physician visits and other healthcare provider contacts. Indirect costs, including the number of days when the patient or their carer was unable to attend to their normal daily activities, were also assessed. The study assumed a European societal perspective (i.e. including direct and indirect costs).. Treatment with SMART resulted in significantly fewer severe exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per patient per year; p = 0.0025). Resource use was low in both groups. Medication costs accounted for the majority of the total costs. The increased effectiveness of SMART was achieved at a reduced or similar cost compared with SFC. SMART dominated when German unit costs were applied (i.e. there was a statistically significant reduction in both costs and number of exacerbations). In all other countries, the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided; however, this difference was not statistically significant.. This analysis demonstrates that, compared with SFC, SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy, Germany, France and the UK. SMART provided a reduction in the number of severe exacerbations per patient per year, at no statistically significant increase in cost - or even at a lower cost - compared with SFC plus as-needed reliever salbutamol.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Cost of Illness; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Economics, Pharmaceutical; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged

To evaluate the efficacy and tolerability of a novel hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) formulation of budesonide (Pulmicort) versus the conventional chlorofluorocarbon (CFC) pMDI formulation in paediatric patients with asthma.. This was a Phase III, multicentre, 12-week, double-blind, randomised, parallel-group study involving children (6-12 years of age) with mild to moderate asthma. Patients received either budesonide HFA pMDI or budesonide CFC pMDI 200 mug twice daily, with or without a spacer (NebuChamber/Nebunette). Primary efficacy endpoint: mean percentage change in forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Secondary efficacy endpoints included changes in FEV(1) per cent of predicted normal, forced vital capacity, morning and evening peak expiratory flow rate, asthma symptoms and use of rescue medication.. A total of 159 patients received treatment (HFA 77, CFC 82). For mean percentage change in FEV(1) from baseline to week 12, the difference between the treatments (CFC pMDI - HFA pMDI) was -3.1% (95% confidence interval [CI] -8.0% to 1.8%) for the full analysis set and was not affected by spacer use. The upper CI was < 10% (the predefined non-inferiority margin), so non-inferiority was demonstrated. Improvements in the secondary efficacy endpoints with both budesonide formulations were not significantly different. In both groups there were similar numbers of adverse events and no evidence of oral candidiasis at week 12.. Treatment with budesonide HFA pMDI is effective and well tolerated in children with asthma and is clinically comparable to budesonide CFC pMDI.

Topics: Aerosol Propellants; Asthma; Bronchodilator Agents; Budesonide; Child; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate; Treatment Outcome

Ciclesonide is a new lung-activated inhaled corticosteroid (ICS) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma. It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability.. This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma.. This 12-week, randomized study was conducted at 62 study sites across Europe. Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled. This study was double blind with respect to the ciclesonide dose and open label for budesonide, as placebofor budesonide was not available. Patients were randomly assigned to receive inhaled ciclesonide 80 or 320 microg QD (morning) or budesonide 200 microg BID for 12 weeks. Efficacy and tolerability assessments were performed at weeks 0 (baseline), 4, 8, and 12. The primary end point was the change from baseline in forced expiratory volume in 1 second (FEV1) at 12 weeks. Secondary end points were changes from baseline in morning peak expiratory flow (PEF), asthma symptom scores, and rescue medication use. Tolerability was assessed throughout the study by monitoring of standard laboratory variables (hematology and biochemistry); physical examination, including vital signs; reporting of adverse events (AEs); and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function.. Five hundred fifty-four patients were randomized (301 men, 253 women; mean age, 41.3 years; ciclesonide 80 microg QD, 182 patients; ciclesonide 320 microg QD, 195; budesonide 200 microg BID, 177). Demographic and baseline clinical characteristics, including age, sex, weight, and (FEV1) were similar between the 3 groups. Compared with baseline values, week-12 FEV1 (least squares mean [LSM] [SEM] A, +0.267 [0.035], +0.256 [0.033], and +0.355 [0.034] L, respectively; all, P<0.001) and morning PEF (LSM [SEM] Delta, +12 [5], +17 [4], and +21 [4] L/min, respectively; all, P

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Child; Double-Blind Method; Female; Glucocorticoids; Humans; Hydrocortisone; International Cooperation; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

Asthmatic children on long-term treatment with inhaled corticosteroids (ICS) may exhibit mild adrenal suppression. We aimed to test the hypothesis that baseline adrenal function of some asthmatic children might be lower than that of others and that this difference might be accentuated by ICS therapy.. A low-dose Synacthen test was performed in 41 prepubertal asthmatic children placed on long-term inhaled budesonide (400 microg/day) prior to the onset of ICS treatment, 6 and 12 months later. Five children withdrew before the 6- and another 2 before the 12-month follow-up.. Low adrenal function was demonstrated in 4 children (9.8%) upon recruitment and in another 8 at the 6-month evaluation (22.2%). Adrenal function normalized in the aforementioned 4 children at the 6-month evaluation, while 6 (17.6%) exhibited suppressed adrenal function at the 12-month evaluation. Three of these patients had also exhibited adrenal suppression at the 6-month visit. A significant improvement in peak cortisol values from baseline to the 6- and 12-month evaluation (95% confidence intervals: -283.9 to -69.0 and -239.8 to -50.8, respectively) was evident when children with suppressed adrenal response at the second or third evaluation were excluded.. In many asthmatic children, adrenal response improves on long-term ICS. The expected adrenal suppression of certain patients on maintenance ICS appears to constitute a separate phenomenon.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Insufficiency; Adrenocorticotropic Hormone; Asthma; Budesonide; Child; Child, Preschool; Cohort Studies; Female; Growth Hormone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunocompromised Host; Immunosuppressive Agents; Longitudinal Studies; Male; Pituitary-Adrenal System; Prospective Studies; Recovery of Function; Remission, Spontaneous; Steroids; Time; Treatment Outcome

The target of anti-inflammatory therapy in asthma is thought to be situated, at least partly, in the lung periphery, and inhaled steroid aerosols are being engineered to reach it. However, the potential effect of such aerosols cannot be fully evaluated by conventional lung function tests because these are insensitive to peripheral lung structure.. A prospective cohort study was conducted to investigate whether ultrafine steroid aerosols can elicit a response in the lung periphery, using a validated multibreath washout technique that can distinguish acinar from conductive lung zone function.. In 30 stable patients with asthma with a wide range of disease severity (FEV(1) 27% to 108% predicted), we assessed conductive and acinar airway function abnormality at baseline, with patients on a standard dry powder steroid aerosol and after switching them to an ultrafine steroid aerosol.. Only in those patients with abnormal acinar airway function at baseline (n = 16) did acinar heterogeneity show a consistent improvement after switching to an ultrafine steroid aerosol; the improvement was also correlated with baseline acinar heterogeneity (r = -0.67; P = .007). Although all patients with asthma also presented conductive airway abnormality at baseline, no changes were observed in this lung zone with the switch to the ultrafine aerosol (P > .1).. Among stable patients with asthma, those with acinar lung zone abnormality at baseline have the potential to receive functional benefit from an ultrafine steroid aerosol. Clinical studies comparing the efficacy of steroid aerosols targeted to the deep lung should at least include a measurement of peripheral lung zone function.. A new noninvasive measure of small airways function reveals why, and for which particular patients with asthma, small steroid aerosol particles can be of therapeutic use.

Topics: Adolescent; Adult; Aerosol Propellants; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Humans; Hydrocarbons, Fluorinated; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Powders; Spirometry

The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available.. The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose.. Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment.. In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively. Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Receptors, Adrenergic, beta-2

Nebulized budesonide (NB) might offer topical anti-inflammatory activity and be an alternative to systemic corticosteroid (SC) in the treatment of acute asthma. The aim of this study was to compare the effect of NB with SC on lung function and clinical findings of adult patients with acute asthma. Thirty patients admitted to clinic with asthma attack (F/M: 26/4; mean age: 47.1 +/- 2.1 years) were enrolled to the study. The patients were randomized into three groups; Group I were treated with NB alone (4 mg/day), Group II SC alone (1 mg/kg/day methylprednisolone), Group III NB plus SC. Pulmonary functions and respiratory symptom scores were measured and recorded before and during 7 days of study. Spirometric parameters significantly improved in all groups at 7th day significantly (p< 0.05) without a difference among groups (p> 0.05). FEV(1) % levels increased significantly at the first day of study in Group I and III (p< 0.05), but didn't change in Group II until 5th day of study. The mean symptom scores decreased significantly at the second day in Group I (p< 0.05), and at the 4th day in other groups. NB with or without SC improved successfully airway obstruction and symptoms in patients hospitalized with acute asthma attack as the 1st treatment day in comparison with SC alone and this effect lasted for 7 days. Regarding the superior safety profile and comparable efficacy with SC, NB might be an alternative to the patients with moderate-severe asthma attacks.

Topics: Acute Disease; Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Female; Humans; Male; Methylprednisolone; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome

We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group.. budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.

Topics: Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Humans; Hydrocortisone; Peak Expiratory Flow Rate; Quality of Life; Treatment Outcome

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bone Density; Bone Resorption; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Osteoporosis; Salmeterol Xinafoate

The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy.. We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 microg and 4.5 microg, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 microg), or budesonide-formoterol (160 microg and 4.5 microg). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more.. Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoterol, respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated.. Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Severity of Illness Index; Terbutaline

The aim of this study was to compare the results of low-dose (LDT) and standard-dose (SDT) ACTH tests in the assessment of adrenal function in 30 asthmatic children (mean age 9.35 +/- 1.9 years, 19 boys) who were treated with budesonide Turbohaler at conventional 400 microg or 600 microg daily doses for 8 weeks by a prospective, randomized, and open parallel study. Budesonide did not lead to any significant suppression of the hypothalamic-pituitary-adrenal (HPA) axis in either treatment group. However, when individual patient values were examined at the end point, peak cortisol concentrations after LDT were below 2 SDs of the pretreatment values in four patients (13.3%). Also, the increment in cortisol values was <200 nmol/l in all four patients. Decreased 24-hour urinary free cortisol excretion provided further evidence for HPA axis suppression in these patients. Two of these four poor responders to LDT showed normal stimulation with SDT. In conclusion, even with moderate doses and short-term use, adrenal suppression may occur in certain susceptible patients. The low-dose ACTH test is more reliable than SDT for the evaluation of such patients.

Topics: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone; Asthma; Budesonide; Child; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System

Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting beta2-agonist with as-needed use of a beta2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled beta2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) > or =20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis Turbuhaler) 4.5 microg as needed (n = 47) or budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg as needed (n = 45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7- -0.7). In the budesonide/formoterol group, use of > or =4 inhalations x day(-1) of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a beta2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Asthma; Breath Tests; Budesonide; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Treatment Outcome

Montelukast is reported to be beneficial in asthma as add-on therapy to inhaled corticosteroids and may reduce the need for the latter.. To evaluate whether a combination of oral montelukast and 200 microg of inhaled budesonide has comparable efficacy to 400 microg of inhaled budesonide alone in children with moderate persistent asthma.. In this prospective, blinded, hospital-based randomized controlled trial, 71 children with moderate persistent asthma were randomized to receive either montelukast, 5-mg chewable tablet, with 200 microg of inhaled budesonide or only 400 microg of inhaled budesonide daily for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score were performed; the frequency and severity of exacerbations were also recorded.. Measurements of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma Symptom Score showed no significant differences between the 2 groups at baseline, during the serial follow-up visits, and at the end of the study. However, children who received montelukast had a greater frequency of exacerbations vs those who did not (33.3% vs 9.1%; P < .01).. The overall control of asthma with 5 mg of oral montelukast and 200 microg of inhaled budesonide is inferior to that with 400 microg of inhaled budesonide in children with moderate persistent asthma.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Cyclopropanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Quinolines; Respiratory Function Tests; Sulfides

Few studies have assessed the effectiveness of inhaled corticosteroid therapy exclusively in Asian patients with asthma. The present analysis compared the efficacy of early intervention with inhaled budesonide in Caucasian and Asian patients over the first 3 years of the inhaled Steroid Treatment As Regular Therapy in early asthma study.. Patients aged 5-66 years with mild persistent asthma of

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asian People; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Forced Expiratory Volume; Growth; Humans; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Treatment Outcome; White People

We evaluated if budesonide inhalation suspension (BIS) reduces the immunogenicity of the varicella vaccine in paediatric patients with asthma. This open-label, parallel-group, cohort study included varicella-naïve (disease and vaccine) children aged 12 months to 8 years with asthma requiring therapy. Patients who received > or = 4 weeks of asthma treatment with BIS 0.25-1 mg daily or non-steroidal conventional asthma therapy (NSCAT) daily or as needed and met eligibility requirements received the varicella vaccine (Varivax) and continued the same asthma treatment for > or = 8 weeks postvaccination. Varicella-zoster virus (VZV) antibody levels were assessed before and 6 weeks after vaccination using a glycoprotein enzyme-linked immunosorbent assay (gpELISA). Adverse events (AEs) were assessed throughout the study. Antibody levels were analysed in 243 of 274 patients who were vaccinated and received treatment. After immunisation, the percentage of patients in each group achieving a 'protective' level of VZV antibody (> or = 5 gpELISA units/ml) was similar: 85% (129/151) in the BIS group and 90% (83/92) in the NSCAT group (relative risk = 0.95; 95% confidence interval 0.86-1.04). Eight patients in each group reported AEs related to varicella vaccination (primarily pyrexia, agitation and injection-site reactions). There were no cases of severe varicella in either group; one case of mild varicella-like rash was reported in a 12-month-old child in the NSCAT group 11 days after vaccination. VZV antibody responses and tolerability to the live varicella vaccine in paediatric asthma patients treated with BIS vs. NSCAT were comparable, demonstrating that young children with asthma receiving nebulised BIS can be immunised effectively with Varivax.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibody Formation; Asthma; Budesonide; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Cohort Studies; Humans; Infant; Patient Compliance

Inhaled corticosteroids (ICSs) are the preferred maintenance therapy for adults and children with mild, moderate and severe persistent asthma, with the addition of a long-acting beta(2)-adrenoceptor agonist to ICS therapy recommended for patients with moderate or severe persistent asthma. The efficacy and safety of the combination of budesonide and formoterol delivered via dry powder inhaler (DPI) is well documented.. To compare the efficacy and safety of budesonide/formoterol pressurised metered-dose inhaler (budesonide/formoterol pMDI; Symbicort pMDI, AstraZeneca LP, Wilmington, DE, USA) with budesonide pMDI (Pulmicort pMDI, Astra [corrected] Zeneca, Lund, Sweden), formoterol DPI (Oxis Turbuhaler, AstraZeneca, Lund, Sweden), budesonide plus formoterol in separate inhalers (budesonide pMDI + formoterol DPI) and placebo.. This was a 12-week randomised, double-blind, double-dummy, placebo-controlled study.. This multicentre study was conducted in the respiratory specialty clinical practice setting.. The study included 596 patients > or =12 years of age with moderate to severe persistent asthma previously receiving ICSs.. After 2 weeks on budesonide pMDI 80 microg x two inhalations (160 microg) twice daily, patients received budesonide/formoterol pMDI 160 microg/4.5 microg x two inhalations (320 microg/9 microg); budesonide pMDI 160 microg x two inhalations (320 microg) + formoterol DPI 4.5 microg x two inhalations (9 microg); budesonide pMDI 160 microg x two inhalations (320 microg); formoterol DPI 4.5 microg x two inhalations (9 microg); or placebo twice daily.. There were two prespecified primary efficacy variables: mean change from baseline in morning predose forced expiratory volume in 1 second (FEV(1)), obtained approximately 12 hours after the most recent administration of study medication at home and immediately before the next administration of study medication at the clinic; and mean change from baseline in 12-hour FEV(1), assessed as the average change in FEV(1) from serial spirometry over the 12-hour period after administration of the morning dose of study medication at the clinic.. Mean changes from baseline in morning predose FEV(1) at end of treatment were greater (p < or = 0.049) with budesonide/formoterol pMDI (0.19L) versus budesonide pMDI (0.10L), formoterol DPI (-0.12L) and placebo (-0.17L). Mean changes from baseline in 12-hour FEV(1) were greater (p < or = 0.001) with budesonide/formoterol pMDI after 1 day (0.37L), 2 weeks (0.34L) and at end of treatment (0.37L) versus budesonide pMDI (0.11, 0.15 and 0.15L) and placebo (0.09, -0.03 and -0.03L), and after 2 weeks and at end of treatment versus formoterol DPI (0.19 and 0.17L). Fewer (p < or = 0.025) patients receiving budesonide/formoterol pMDI versus monoproducts or placebo met worsening asthma criteria. Results were similar in the budesonide/formoterol pMDI group and the budesonide pMDI + formoterol DPI group on all measures. All treatments were well tolerated with similar safety profiles.. In this population, twice-daily budesonide/formoterol pMDI provides asthma control significantly greater than the monocomponents or placebo and comparable with budesonide pMDI + formoterol DPI. Safety profiles were similar for all treatments.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Placebos; Respiratory Function Tests; Sweden

The long-acting beta2-agonist (LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma.. In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV1) of > or =30% at enrollment (Visit 1) and three subsequent study visits (Visits 2-4). Immediately after each provocation at Visits 2-4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 microg (via Turbuhaler), two inhalations of salbutamol 100 microg (via a pressurised metered-dose inhaler [pMDI]) or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV1 and breathlessness (using the Borg scale) was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment.. Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness) rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p < 0.0001, respectively, versus placebo), with similar rapid increases in FEV1 (both active treatments p < 0.0001 versus placebo). The median time to 50% recovery in Borg score after methacholine provocation was 3 minutes with budesonide/formoterol, 2 minutes with salbutamol and 10 minutes with placebo. All treatments and procedures were well tolerated.. Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The perception of relief, as confirmed by objective lung function assessment, provides evidence that budesonide/formoterol can be used as reliever medication in asthma.

Topics: Adolescent; Adult; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Dyspnea; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Methacholine Chloride; Middle Aged; Placebo Effect; Treatment Outcome

A fixed combination of long-acting beta(2)-agonists (LABA) plus inhaled corticosteroids (ICS) has never been proven to reduce asthma exacerbations vs ICS alone in children. This 12-month, double-blind, randomized study in 341 children (age range, 4 to 11 years) with asthma uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort; AstraZeneca R&D, Lund, Sweden] could reduce exacerbations.. Patients received SMART (budesonide/formoterol 80/4.5 microg qd maintenance plus additional inhalations for symptom relief), budesonide/formoterol 80/4.5 microg qd for maintenance (fixed combination), or higher-dose budesonide 320 microg qd (fixed-dose budesonide). Blinded as-needed medication (terbutaline 0.4 microg) was provided in both fixed-dose groups.. SMART prolonged the time to first exacerbation vs fixed-dose budesonide (p = 0.02) and fixed-dose combination (p < 0.001). Rates of exacerbation requiring medical intervention were reduced by 70 to 79% with SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs 0.28/patient and 0.40/patient, respectively; both p < 0.001). Mild exacerbation days and awakenings were significantly lower with SMART; yearly growth improved by 1.0 cm vs fixed-dose budesonide (p < 0.01).. The SMART regimen using budesonide/formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher fixed-dose ICS alone in children with asthma.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Child, Preschool; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Prospective Studies; Terbutaline

Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists. However, fluctuating asthma control still occurs. We hypothesized that in patients receiving low maintenance dose budesonide/formoterol (bud/form), replacing short-acting beta2-agonist (SABA) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy, thereby reducing exacerbations. In this double-blind, randomized, parallel-group study, 2,760 patients with asthma aged 4-80 years (FEV1 60-100% predicted) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 microg twice a day (bud/form + SABA) or bud 320 microg twice a day (bud + SABA) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed (bud/form maintenance + relief). Children used a once-nocte maintenance dose. Bud/form maintenance + relief prolonged time to first severe exacerbation (p < 0.001; primary endpoint), resulting in a 45-47% lower exacerbation risk versus bud/form + SABA (hazard ratio, 0.55; 95% confidence interval, 0.44, 0.67) or bud + SABA (hazard ratio, 0.53; 95% confidence interval 0.43, 0.65). Bud/form maintenance + relief also prolonged the time to the first, second, and third exacerbation requiring medical intervention (p < 0.001), reduced severe exacerbation rate, and improved symptoms, awakenings, and lung function compared with both fixed dosing regimens.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Proportional Hazards Models; Regression Analysis; Safety

Topics: Asthma; Bone Density; Budesonide; Drug Therapy, Combination; Etidronic Acid; Glucocorticoids; Humans; Osteoporosis; Prednisone

To compare the safety of budesonide inhalation suspension (BIS) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze.. In this multicenter, randomized, double-blinded, parallel-group, placebo-controlled study, 141 patients received 0.5 mg BIS (n = 48), 1.0 mg BIS (n = 44), or placebo (n = 49) once daily for 12 weeks. The primary variable was adrenal function, based on cosyntropin-stimulated plasma cortisol levels. Spontaneous adverse events and clinical laboratory findings also were monitored.. Overall, the types and frequencies of adverse events reported during the study were comparable across treatment groups. The response to cosyntropin stimulation was similar across treatment groups, with no significant difference between BIS treatment and placebo.. The safety profile of BIS was similar to that of placebo, with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze.

Topics: Administration, Inhalation; Adrenal Glands; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Infant; Male; Nebulizers and Vaporizers; Respiratory Sounds

Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens.. Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC(20)), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated.. Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen.. The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens.

Topics: Acetates; Allergens; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Eosinophils; Exhalation; Female; Humans; Lung; Male; Methacholine Chloride; Nitric Oxide; Quinolines; Respiratory Function Tests; Sputum; Sulfides

Bronchial asthma is characterized by airway inflammation, notably because of eosinophils and T cells. Thymus and activation-regulated chemokine (TARC) is known to selectively attract Th2 cells, and is increased in response to interleukin (IL)-4 and IL-13, which share a common receptor, IL-4 receptor alpha (IL-4Ralpha). While corticosteroids have proven, very effective in modifying airway inflammation, the effect of corticosteroids on TARC in asthmatics has been little studied.. We examined the effects of inhaled budesonide (BUD) on the expression of TARC and the number of inflammatory cells in bronchial biopsy specimens taken from asthma patients.. Inhaled BUD 800 mug daily, or placebo was administered for 3 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined by immunocytochemistry.. We observed a significant decrease in the epithelial expression of TARC (P < 0.01) in the BUD group compared with the placebo group. This was accompanied by decreases in the number of eosinophils (P < 0.01), CD3(+) T cells (P < 0.05), and CD4(+) T cells (P < 0.01). A significant correlation was found between changes in epithelial TARC and in IL-4Ralpha immunoreactivity (r(s) = 0.66, P < 0.01).. These findings suggest that corticosteroid asthma treatment can reduce infiltration of the airway by inflammatory cells, an effect modulated by down-regulation of bronchial epithelial TARC expression.

Topics: Administration, Inhalation; Adult; Asthma; Biopsy; Bronchi; Bronchodilator Agents; Budesonide; CD3 Complex; CD4 Lymphocyte Count; Chemokine CCL17; Chemokines, CC; Double-Blind Method; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; T-Lymphocytes

The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study is a worldwide, randomized, prospective study to investigate early intervention with inhaled corticosteroids in recent-onset mild persistent asthma.. To evaluate the safety and tolerability of long-term treatment with once-daily budesonide therapy in patients with mild persistent asthma.. Patients aged 5 to 66 years with mild persistent asthma for fewer than 2 years and no previous regular corticosteroid treatment received budesonide or placebo once daily for 3 years, in addition to their usual asthma therapy. The daily budesonide dose was 200 microg for children younger than 11 years and 400 microg for those 11 years or older.. Overall, 7,221 patients were included in the safety analysis, and a total of 21,520 adverse events were reported (10,850 in the budesonide group and 10,670 in the placebo group). The most commonly reported events included respiratory infections, rhinitis, pharyngitis, bronchitis, viral infections, and sinusitis. The number of deaths and serious adverse events were similar for children and adults in both treatment groups. Fewer asthma-related serious adverse events were reported with budesonide (162) compared with placebo (276). Oral candidiasis was reported more frequently with budesonide (1.2%) than with placebo (0.5%); the frequencies of other adverse effects previously reported to be associated with inhaled corticosteroids (psychiatric disorders, skin disorders, and allergic reactions) were similar.. Three-year treatment with budesonide once daily (200 or 400 microg) is safe and well tolerated in children and adults with newly detected mild persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Middle Aged; Prospective Studies

Some studies have demonstrated that the function of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is significantly impaired in patients with oral corticosteroid (CS)-induced osteoporosis. The aim of study was to investigate the effects of long-term therapy with inhaled CSs (ICSs) on the hypothalamic-pituitary-GH axis by the GH response to GH-releasing hormone (GHRH), as well as bone turnover, in adult asthmatic patients.. Cross-sectional study.. Twenty-seven adult subjects with mild-to-moderate persistent asthma (long-term ICS therapy [ie, > 1 year], 20 patients; naive to ICS treatment, 7 patients) and 10 control subjects.. Each subject underwent testing with an IV bolus (1 mug/kg) injection of human GHRH, and samples of GH were taken 15 min before the GHRH injection, at 0 min (ie, at the time of GHRH injection), and at 15, 30, 45, 60, and 90 min after injection to obtain values for peak GH and DeltaGH. At baseline, samples of serum IGF-1 and blood-urine were collected for bone turnover markers.. The GH response to GHRH was significantly reduced in asthmatic patients receiving ICSs (peak GH, p < 0.05; and DeltaGH, p < 0.01) in comparison with control subjects and asthmatic patients who were naive to ICS therapy (peak GH and DeltaGH, p < 0.01). Baseline IGF-1 levels were similar in the three groups. Serum osteocalcin, a marker of bone formation, was significantly reduced (p < 0.01) and correlated with GH peak (r(2) = 0.34; p = 0.007) in asthmatic patients who were treated with ICSs.. We conclude that GH secretion in response to GHRH is significantly reduced in adult asthmatic patients receiving therapy with ICS and that such inhibition could play a negative role in bone metabolism.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone Density; Bone Remodeling; Budesonide; Cross-Sectional Studies; Female; Fluticasone; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Long-Term Care; Male; Middle Aged; Osteocalcin; Statistics as Topic

Neutrophils, in addition to eosinophils, are prominent in the airways of patients with severe asthma who are usually on long-term oral and inhaled corticosteroid treatment. We determined whether inhaled or oral corticosteroid therapy can induce airway neutrophilia.. We performed two separate placebo-controlled studies in which patients with mild asthma were treated with either prednisolone (30mg per day for 7 days; n = 9) or placebo tablets (n = 8), or with either inhaled budesonide (800 microg twice daily for 4 weeks; n = 6) or inhaled placebo (n = 6). Fiberoptic bronchoscopy was performed before treatment and at day 7 of oral treatment, and at day 28 of inhaled therapy. Bronchial sections were immunostained with an antibody to major basic protein for eosinophils, and with an antibody to neutrophil elastase for neutrophils. Induced sputum was obtained in the prednisolone study.. Neutrophils in airway submucosa increased after prednisolone from median 76 to 140/mm2 (P = 0.05); this change was higher than that after placebo (P = 0.04). Eosinophils decreased from 24 to 9/mm2 (P = 0.03), but this was not significantly different from placebo. Eosinophils and neutrophils, and levels of IL-8 and myeloperoxidase in induced sputum did not change after prednisolone. There was no change in neutrophil counts after budesonide, but the reduction in eosinophils was greater than placebo (P = 0.05). Budesonide improved bronchial responsiveness, but prednisolone did not.. Corticosteroid therapy by the oral but not inhaled route can induce neutrophil recruitment into the airways of patients with mild asthma. This could explain the increase in airway neutrophils observed in severe asthmatics treated with oral corticosteroids.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Neutrophils; Prednisolone; Sputum

Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established.. We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy.. In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 microg of budesonide twice daily, 200 microg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period.. When compared with placebo (26% +/- 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% +/- 10%, P = .001) but not after budesonide treatment (23% +/- 13%, P = .08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection ( P = .62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments ( P = .001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment.. The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy.

Topics: Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Time Factors

Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period.. In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV1) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life.. The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV1 (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured.. It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Indoles; Male; Peak Expiratory Flow Rate; Phenylcarbamates; Sulfonamides; Tosyl Compounds

To investigate the long term efficacy as well as the side-effects of small dose budesonide turbuhaler in mild bronchial asthma.. Fifty-two patients with mild asthma were randomly divided into groups A, B and C. Twenty-two cases in group A received 200 microg budesonide turbuhaler by inhalation every night. Fifteen cases in group B received oral prednisone 5 mg/d and theophyllin control release tablet 0.2 g twice daily, as well as ventolin aerosol inhalation 200 microg three times daily during asthmatic attack. Fifteen cases in group C received no glucocorticoids, but theophyllin control release tablet 0.2 g twice daily as well as ventolin aerosol inhalation (200 microg/d) were given during asthmatic attack. All three groups received treatment consecutively for 3 years, and followed for one year after stopping treatment. During the total 4 years, pulmonary function measurements (FEV1, Raw, Gaw), bronchial hyperreactivity (BHR), clinical effects, plasma cortisol level and the activated reaction of ACTH were evaluated.. (1) Before the treatment, BHR of the three groups were similar, with most cases graded III-IV, being 91% (20/22), 100% (15/15) and 93% (14/15) respectively. After the treatment, the BHR of 18 (82%) cases of group A was reduced to grades I-II. However, 13 cases (87%) of group B still remained at grades III-IV and 15 cases (100%) of group C were still at grades III-IV. The results of the three groups showed a significant difference (P < 0.01). (2) Compared to measurements before the treatment, Raw was (623 +/- 103)% vs (158 +/- 24)% in group A, (605 +/- 90)% vs (340 +/- 61)% in group B, and (638 +/- 108)% vs (420 +/- 81)% in group C, the difference among the three groups being significant (P < 0.01). (3) Compared to the measurements before the treatment, Gaw was (22 +/- 4)% vs (83 +/- 15)% in group A, (27 +/- 6)% vs (42 +/- 9)% in group B, and (27 +/- 5)% vs (31 +/- 6)% in group C, the difference among the three groups being significant (all P < 0.01 respectively). (4) Compared with the measurements before the treatment, FEV1 was (2.3 +/- 0.4) L vs (2.9 +/- 0.4) L in group A, (2.3 +/- 0.4) L vs (2.6 +/- 0.4) L in group B, and (2.3 +/- 0.4) L vs (2.7 +/- 0.4) L in group C, the difference among the three groups being significant (P < 0.01). (5) With asthmatic symptom control as the criteria of therapeutical effects, the effective rate of group A, B and C were 91%, 53% and 33% respectively, which showed significant difference among the three groups (all P < 0.01 respectively). (6) The plasma cortisol levels of group A and B were (326 +/- 103) nmol/L and (308 +/- 29) nmol/L before treatment, compared with (318 +/- 78) nmol/L and (299 +/- 98) nmol/L after treatment, the difference in group A or in group B was not significant (all P > 0.05). When the measurements before and after treatment were compared, the cortisol levels of group A and B were (365 +/- 102) nmol/L vs (373 +/- 102) nmol/L and (343 +/- 79) nmol/L vs (346 +/- 103) nmol/L respectively after the stimulation of ACTH, which showed no significant changes even after the stimulation of ACTH (all P > 0.05).. Long term small dose budesonide turbuhaler inhalation could effectively decrease BHR and the Raw, while increase the Gaw of asthmatic patients, hence improving the pulmonary function and preventing acute attack. In addition, it did not induce suppression of HPAA axis function in the patients.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Resistance; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Budesonide; Child; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hydrocortisone; Lung; Male; Middle Aged; Prednisone

To evaluate the efficacy and the safety of low dose salmeterol/fluticasone (SM/FP) combination therapy as compared to morate dose of budesonide (BUD) in the management of adult asthma.. A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted. 398 patients (18 - 70 years) were given SM/FP (50/100 microg) twice daily via Accuhaler or BUD 400 microg twice daily via Turbuhaler.. The morning and the evening peak expiratory flow (PEF) measurements both increased significantly (P < 0.01) in the SM/FP group, and the increase was greater than that in the BUD group. The significant benefit of SM/FP was evident from the first week. SM/FP led to a more significant reduction in the use of rescue medication and in the day- and night-time asthma symptom scores, as compared to budesonide. Both treatments were well tolerated, and the adverse reactions showed no significant difference between the two groups.. Combination use of low doses of SM/FP is a better choice for the control of asthma. The addition of a low-dose long-acting beta(2) agonist is superior to the simple increase of the dosage of inhaled corticosteroids.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Powders; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.

Topics: Administration, Inhalation; Adult; Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Leukotriene Antagonists; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate; Respiratory Function Tests; Salmeterol Xinafoate

In asthma, the response to beta-agonists acting at beta2-adrenergic receptors (beta2AR) displays extensive interindividual variation. One effector for airway beta2AR, adenylyl cyclase type 9 (AC9), was considered a candidate locus for predicting beta-agonist efficacy in the absence and presence of corticosteroid treatment. One non-synonymous AC9 polymorphism has been identified, which results in substitution of Met for Ile at amino acid 772. Under standard culture conditions in stably transfected cells, we found decreased catalytic activity of Met772. However, cells cultured in the presence of glucocorticoid expressing Met772 had a significantly increased albuterol-stimulated adenylyl cyclase response (approximately 80%) when compared with those expressing Ile772 (approximately 20%, P=0.02). An equivalent increase in beta2AR expression was observed in both lines due to glucocorticoid, but AC9 expression was unaffected. The hypothesis that Met772-AC9 is associated with an improved albuterol bronchodilator response in asthmatics was investigated in 436 asthmatic children who were followed for 4 years and randomized to receive placebo or the inhaled corticosteroid budesonide. Met772 carriers on budesonide showed a significant improvement in forced expiratory volume in 1 s (P=0.005). Moreover, a highly significant interaction (P=0.002) was found for budesonide treatment and the AC9 polymorphism. These in vitro and human association studies are consistent with this AC9 polymorphism altering albuterol responsiveness in the context of concomitant inhaled corticosteroid administration, which is a common asthma regimen. The Met772-AC9 polymorphism represents one of most likely several multi-gene polymorphisms along the receptor-relaxation axis, which together may provide for a composite pharmacogenetic index for asthma therapy.

Topics: Adenylyl Cyclases; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Amino Acid Substitution; Asthma; Bronchodilator Agents; Budesonide; Catalytic Domain; Cells, Cultured; Child; Child, Preschool; Cohort Studies; Forced Expiratory Volume; Humans; Isoenzymes; Lung; Pharmacogenetics; Polymorphism, Genetic; Signal Transduction

A patient-driven, adjustable maintenance dosing (AMD) approach to asthma therapy, in which the dose is adjusted by patients according to the severity of their symptoms, has recently been compared with fixed-dose therapy in open-label studies.. This study used a double-blind, double-dummy design to compare the efficacy of 2 treatment approaches: stable dosing of salmeterol/fluticasone propionate (SAL/FP) and AMD of formoterol/budesonide (FOR/BUD).. This was a 1-year, multicenter, randomized, double-blind, double-dummy study in adult patients with symptomatic asthma that was not controlled by therapy with 200 to 500 microg/d inhaled corticosteroid (ICS) plus a long-acting beta2 agonist, or with >500 to 1000 microg/d ICS alone. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 microg BID or 2 inhalations of FOR/BUD 6/200 microg BID, both delivered via dry powder inhaler devices. After 4 weeks of stable dosing in both groups, eligible patients continued the study for an additional 48 weeks, receiving either a stable dose of SAL/FP or AMD of FOR/BUD. According to the AMD treatment plan, patients initially halved their dose and subsequently stepped up or down as indicated by the presence or absence of nocturnal awakenings due to asthma, frequency of rescue medication use, and changes in morning peak expiratory flow (PEF). The primary end point was the percentage of symptom-free days. Other parameters included daily asthma symptom scores, morning PEF, percentage of days free of rescue medication use, daily rescue medication use, percentage of nighttime awakenings due to asthma, percentage of weeks with well-controlled asthma, and number of exacerbations requiring oral corticosteroids or emergency department (ED) visits/hospitalizations. Tolerability was assessed in terms of adverse events spontaneously reported or elicited at clinic visits.. The intent-to-treat population comprised 688 patients (344 per treatment arm) with a mean age of 45 years and a mean baseline forced expiratory volume in 1 second 81% of the predicted normal value. After 4 weeks' stable dosing, 581 patients (295 SAL/FP, 286 FOR/BUD) continued beyond visit 3 into the remaining 48-week treatment period. Over weeks 1 through 52, patients receiving stable dosing of SAL/FP had a significantly greater percentage of symptom-free days compared with those receiving AMD of FOR/BUD (median, 58.8% vs 52.1%, respectively; P = 0.034). The incidence of asthma exacerbations requiring oral steroids or an ED visit/hospitalization was 47% lower with SAL/FP compared with FOR/BUD (adjusted annual mean rate, 0.18 vs 0.33; P = 0.008). During weeks 5 through 52, patients in the FOR/BUD AMD group used a mean of 1.8 inhalations/d (equivalent to BUD 360 microg/d), and 235 (82.2%) patients stepped down to 1 inhalation/d. Mean (SD) daily ICS exposure over 52 weeks was 463 (81) microg FP and 480 (238) microg BUD in the respective treatment arms.. In this adult population with persistent asthma, stable dosing of SAL/FP 50/250 microg BID resulted in significantly greater increases in symptom-free days, days free of rescue medication, and morning PEE, as well as almost halving the exacerbation rate, compared with AMD of FOR/BUD 6/200 microg. The results suggest that there is a minimum daily amount of maintenance therapy necessary to prevent exacerbations in adults with persistent asthma.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Self Administration; Treatment Outcome

Since IgE is considered to play a crucial role in allergic immune responses, the reduction of free IgE level has been an attractive target in the treatment of allergic diseases. The present study was conducted to determine the effects of a 6-month treatment with different doses of inhaled budesonide and montelukast sodium in children with newly diagnosed atopic asthma.. In this randomized, double-blind, double-dummy trial, 51 children with newly diagnosed asthma and sensitivity to house-dust mites were randomly allocated to receive budesonide (in two different doses 400 or 800 mcg) or montelukast for 6 months. The primary end point was the level of serum total and specific IgE before and after treatment. The secondary end points were clinical parameters and forced expiratory volume in 1s (FEV1).. After 6 months of treatment, a high dose of inhaled corticosteroid and montelukast, significantly decreased levels of total and specific IgE. Medium dose of inhaled corticosteroid had no effect on total and specific IgE serum level. Clinical score and FEV1 significantly improved after 6 months of treatment with medium (P = 0.002) and high dose (P = 0.001) of inhaled budesonide and montelukast (P = 0.002). There were no differences between groups in changes of all clinical parameters after treatment.. Only high doses of inhaled corticosteroids and montelukast decreased the serum IgE levels. Perhaps long-term treatment with montelukast will be beneficial to asthma patients by decreasing IgE levels.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Anti-Asthmatic Agents; Antigens, Dermatophagoides; Asthma; Budesonide; Child; Child, Preschool; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Immunoglobulin E; Male; Quinolines; Severity of Illness Index; Sulfides; Treatment Outcome

Although inhaled corticosteroids are useful and effective in the prophylaxis of childhood asthma, there is a dearth of information regarding the duration of treatment. The present study was undertaken to assess the possibility of successful withdrawal of inhaled corticosteroids in childhood asthma following good control of the disease.. The study was carried out at the Asiri Hospital, Colombo, Sri Lanka and was a prospective observational clinical study. The participants were consecutive children with documented moderately severe and severe asthma seen over a period of 4 years from January 1990 and followed up to December 2003. Patients were allocated randomly to receive either beclomethasone dipropionate or budesonide. Initial dose of the selected drug was 300, 400 or 600 microg/day, depending on the child's age. After a period of stabilization, the dose was reduced from the starting dose to a maintenance level of 200, 300 or 400 microg/day, respectively. Once sustained control had been maintained for a period ranging from 9 to 18 months, gradual withdrawal was attempted. The dosage was reduced by 50-100 microg each time, at intervals of 3 months. Long-term follow up was maintained following withdrawal of inhaled corticosteroids. Breakthrough wheezing, acute severe attacks, hospitalization for wheezing and absence from school were used to assess the response.. Eighty-six children were recruited into the study. Eighty children responded well. The initial period on a high dose of corticosteroid was 8.4 months (range 4-12 months) and the average period of maintenance dosing was 11.7 months (range 9-18 months). The average time taken for withdrawal was 12.6 months (range 9-18 months). Successful withdrawal was achieved in 73 children. In this group, the mean total duration of treatment was 27.4 months (range 20-44 months). Up to December 2003, the subjects had been observed for an average period of 97.1 months (range 86-121 months) following withdrawal of inhaled corticosteroids. Of the 73 children in whom corticosteroids were withdrawn, 57 (78%) have remained well without any episodes of wheezing, and 14 (19%) have had mild episodes of wheezing that were easily controlled by bronchodilators. No patient needed hospitalization, long-term treatment or systemic corticosteroids. In two (3%) patients, it was necessary to restart inhaled corticosteroids because of troublesome recurrences.. It is possible to gradually withdraw inhaled corticosteroids in a significant proportion of asthmatic children once good control has been sustained on a maintenance dose for a considerable period.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glucocorticoids; Humans; Infant; Male; Observation; Prospective Studies; Time Factors; Treatment Outcome

Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma.. We evaluated whether titrating steroids on FENO improved asthma management in children.. Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FENO group (n=39) in which treatment decisions were made on both FENO and symptoms, or to a symptom group (n=46) treated on symptoms only. Children were seen every 3 months over a 1-year period.. Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose.. Changes in steroid dose from baseline did not differ between groups. In the FENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change in FEV1 was not significantly different between groups. The FENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FENO increased in the symptom group; the change in FENO from baseline differed between groups (p=0.02).. In children with asthma, 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.

Topics: Adolescent; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchial Hyperreactivity; Budesonide; Child; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Nitric Oxide; Prednisone

Bronchial hyperresponsiveness to adenosine monophosphate, an indirect measure of airway inflammation, is a sensitive marker of inhaled corticosteroid efficacy.. To evaluate the relative therapeutic efficacy of budesonide delivered via Clickhaler and Turbuhaler dry powder inhalers in patients with mild-to-moderate persistent asthma.. In a double-masked, dose-response crossover study, 27 patients received inhaled budesonide in cumulative sequential doubling dose increments, 2 weeks per dose, of 200, 400, and 800 microg/d. Each treatment block was preceded by 1- to 3-week placebo run-in and washout periods. End points were measured after each placebo (ie, baseline) and treatment period. Adenosine monophosphate bronchial challenge was the primary outcome, and exhaled nitric oxide, serum eosinophilic cationic protein, spirometry, domiciliary peak expiratory flow, symptoms, and rescue medication use were the secondary outcomes.. For the adenosine monophosphate provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20), a significant overall dose-response effect (P = .006) was found, and there was no significant difference between the devices (P = .8). The relative microgram dose potency ratio between Clickhaler and Turbuhaler was 1.11 (95% confidence interval [CI], 0.50-2.46). After administration of the highest dose of budesonide, the mean doubling dilution shift in adenosine monophosphate PC20 from placebo baseline was 3.46 (95% CI, 2.66-4.27) with the Clickhaler vs 3.41 (95% CI, 2.47-4.35) with the Turbuhaler. A significant overall dose-response effect was demonstrated for exhaled nitric oxide (P = .03) but not for any of the other secondary outcome measures. There were no significant differences between the devices for any of the outcome measures.. Inhaled budesonide exhibited overall dose-response effects on adenosine monophosphate PC20 delivered via Turbuhaler and Clickhaler, with no significant difference between the devices.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchi; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Powders

To compare the costs and effectiveness of adjustable maintenance dosing with budesonide/formoterol in a single inhaler versus fixed dosing in adults with asthma.. In this prospective, randomised, open-label, parallel-group, multicentre trial conducted in Germany, patients with asthma received budesonide/formoterol 160 microg/4.5 microg in a single inhaler (Symbicort Turbuhaler with two inhalations twice daily for a 4-week run-in period. Patients were then randomised to either adjustable maintenance dosing (one inhalation twice daily, stepping up to four inhalations twice daily for 1 week if asthma worsened; n=1679) or fixed dosing (two inhalations twice daily; n=1618) for 12 weeks. The primary efficacy variable was the change in health-related quality of life (HR-QOL), measured using the Asthma Quality of Life Questionnaire (standardised) during the randomised treatment period. Resource utilisation data were collected in parallel and combined with German unit costs to estimate direct and indirect costs (year 2001 values).. Both treatment regimens were equally effective in maintaining HR-QOL and asthma control during the randomised treatment period. However, overall, patients in the adjustable maintenance dosing group took fewer daily inhalations of budesonide/formoterol than those in the fixed-dosing group (mean: 2.63 vs 3.82 inhalations; p<0.001). Adjustable maintenance dosing was associated with significantly lower asthma-related direct costs compared with fixed dosing (mean: 221 euro vs 292 euro; p<0.001). This pattern was maintained when patients were stratified into those with peak expiratory flow (PEF) of 60% to <80% predicted normal and those with PEF of>/=80% predicted normal and when total costs were considered.. Adjustable maintenance dosing with budesonide/formoterol in a single inhaler maintained HR-QOL in adult patients with asthma at a significantly lower cost than fixed dosing.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Germany; Humans; Male; Metered Dose Inhalers; Middle Aged; Primary Health Care; Quality of Life

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Cyclopropanes; Female; Humans; Male; Middle Aged; Quinolines; Respiratory Function Tests; Single-Blind Method; Sulfides; Time Factors

To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation.. The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4-15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment.. Improvement of morning PEF was significantly higher in patients treated with FP (p=0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p=0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression.. A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation

Topics: Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Circadian Rhythm; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index; Single-Blind Method

The use of combination inhaled corticosteroid/long-acting beta-agonist therapy within the framework of a self-management plan has yet to be investigated.. In this randomized open-label study, 69 adult asthmatic patients taking >or= 1,000 microg per day of beclomethasone dipropionate (BDP) or equivalent were treated for 3 months with Symbicort Turbuhaler (200 microg budesonide/6 microg formoterol). Patients were assigned to one of two self-management plans, based on either a fixed or adjustable dose regimen. The primary outcome variable was episode-free days.. Both regimens resulted in good asthma control, at least comparable to that obtained with previous high dose inhaled corticosteroid therapy. There were no significant differences in clinical outcome measures between the regimens. The mean (+/- SD) usage of Symbicort was similar for the fixed and adjustable dose regimens (3.8 +/- 0.68 vs 3.6 +/- 1.54 puffs per day, respectively).. We conclude that Symbicort is effective when administered as either a fixed or adjustable dose regimen as part of a self-management plan.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Drug Combinations; Ethanolamines; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pilot Projects; Respiratory Function Tests; Self Care; Treatment Outcome

Therapy for asthma often includes the combined use of glucocorticoids and leukotriene receptor antagonists. The short-term, combined effects of these drugs on cytokine secretion and lymphocyte proliferation are ill-defined. The aim of this study was to analyze allergen and mitogen-induced cytokine secretion and lymphocyte proliferation in asthmatics and to determine the effect of combined therapy on these immune responses. Peripheral blood mononuclear cells were isolated from mild, persistent adult asthmatics (n = 28) and analyzed for cat allergen (Fel d 1) and mitogen (phytohemagglutinin) induced IL-13 and IFN-gamma secretion and lymphocyte proliferation. Samples were analyzed before and after 10 days of therapy with oral zafirlukast, prednisone (0.5 mg/kg/day), and inhaled budesonide (1600 mcg/day). Both Fel d 1 and mitogen stimulation resulted in IL-13 and IFN-gamma secretion. Combination drug therapy resulted in a significant decrease in allergen-induced IFN-gamma secretion (p = 0.018) and allergen-specific lymphocyte proliferation (p = 0.02), while IL-13 secretion was unchanged (p = 0.109). This study indicates a role for Th1 cytokines as well as Th2 cytokines in the allergic response.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Drug Therapy, Combination; Female; Glucocorticoids; Glycoproteins; Humans; Indoles; Interferon-gamma; Interleukin-13; Leukocytes, Mononuclear; Leukotriene Antagonists; Lymphocyte Activation; Male; Middle Aged; Phenylcarbamates; Phytohemagglutinins; Prednisone; Sulfonamides; Tosyl Compounds

Adding inhaled long-acting beta2-agonists to a low dose of inhaled corticosteroids (ICSs) results in better asthma control than increasing the dose of ICSs. An important, but as yet unresolved, question is whether this is due to an additional reduction of airway inflammation.. Double-blind, parallel-group trial.. Forty asthma patients (FEV1, 50 to 90% predicted; provocative concentration of a substance [methacholine] causing a 20% fall in FEV1 of < 8 mg/mL; no ICSs in the last 4 weeks).. Randomization to 8 weeks of treatment with 100 microg of budesonide bid plus placebo (BUD200) or 100 microg of budesonide bid plus 12 microg of formoterol (BUD200 + F). Then the dose of budesonide (BUD) was increased to 400 microg bid in both groups for another 8 weeks. Bronchial biopsy specimens were collected before, and after 8 and 16 weeks of treatment. Eosinophils (major basic protein [MBP]) and mast cells (tryptase) were analyzed by immunohistochemistry.. BUD200 reduced the MBP staining (p = 0.008) and tryptase staining (p = 0.048) in the epithelium compared to baseline levels. There were no significant differences between the BUD200 and BUD200 + F groups. In both groups, increasing the dosage of BUD to 800 microg had no significant additional antiinflammatory effect.. Our results demonstrate that BUD administered at a low dose has significant antiinflammatory effects in patients with mild asthma. No significant additional antiinflammatory effects could be demonstrated either by adding formoterol or by increasing the dose of BUD.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Bronchi; Budesonide; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Pneumonia; Respiratory Function Tests

Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.

Topics: Adult; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Equipment Design; Female; Forced Expiratory Volume; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Radiopharmaceuticals; Technetium

Inflammatory and structural changes of the airway mucosa are chronic features of asthma. The mechanisms underlying these changes and their modulation by steroid prophylaxis have not been clarified.. We postulated that asymptomatic ongoing allergen exposure could drive airway inflammation as well as changes in the extracellular matrix (ECM), and that inhaled steroids could prevent this.. Therefore, we exposed patients with mild asthma to 2 weeks of repeated low-dose allergen, with concomitant inhaled steroid or placebo treatment. Bronchial biopsies, which were taken before and after this exposure, were stained and digitally analysed. The ECM proteins in asthmatics were also compared with a normal control group.. Low-dose allergen exposure alone resulted in a significant increase of bronchial epithelial macrophages. Despite ongoing allergen exposure, inhaled steroids reduced the numbers of mucosal eosinophils, neutrophils and T lymphocytes. At baseline, the mean density of the proteoglycans (PGS) biglycan and decorin were, respectively, higher and lower in the bronchial mucosa of asthmatics as compared with normal controls. Steroid treatment, during allergen exposure, increased the mean density of the PGS biglycan and versican.. We conclude that chronic allergen exposure induces inflammatory changes in the bronchial mucosa. Despite ongoing allergen exposure, steroid treatment decreases mucosal inflammatory cells while altering PG density. The latter observation highlights the need to examine steroid-induced changes closely in the airway structure in patients with asthma.

Topics: Administration, Inhalation; Allergens; Anti-Inflammatory Agents; Asthma; Biopsy; Bronchi; Bronchoscopy; Budesonide; Double-Blind Method; Extracellular Matrix; Fibronectins; Glucocorticoids; Goblet Cells; Humans; Inhalation Exposure; Mucous Membrane; Proteoglycans; Respiratory Mucosa

The acute anti-inflammatory effects of inhaled steroids at high doses and their use at home and as emergency treatment of acute asthma attacks in children have been evaluated in many clinical studies. However very little is known about their additional bronchodilator response to systemic steroids plus nebulized salbutamol in the early management in children. Asthmatic patients aged between 5-15 years were investigated in a double-blind, placebo-controlled fashion. Both the study group (Group I) and the control group (Group II) received three consecutive doses of nebulized salbutamol (0.15 mg/kg/dose) and one dose of parenteral methylprednisolone (1 mg/kg/dose, intramuscularly). After this treatment, nebulized budesonide (1 mg/dose) was administered to patients in the study group and placebo (nebulized saline) was administered to patients in the control group. Pulmonary index scoring and peak flow meter was performed to both groups before and after the treatment. There were twelve patients in Group I (mean age: 7.90 +/- 2.34 years) and fourteen patients in Group II (mean age: 9.36 +/- 2.55 years). There was no difference between the two groups with respect to age (p = 0.1421), gender (p = 1.000) and inhaled steroid prophylaxis rate (p = 0.2177). No statistically significant difference was detected between the two groups with respect to the pulmonary index score (p = 0.3528). Yet, there was a statistically significant difference between the two groups with respect to the increase in PEFR (p = 0.0155). The positive acute effect of nebulized budesonide in addition to systemic steroids and nebulized salbutamol in improving the spirometric indices in asthmatic children is an encouraging finding for further investigations of its routine use in the pediatric emergency department.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

This 12-month dose-titration study assessed the effectiveness of budesonide/formoterol for maintenance plus relief with a control group using salmeterol/fluticasone for maintenance plus salbutamol for relief. Adolescents and adults (n = 2,143; mean forced expiratory volume in one second (FEV1) 73% predicted; mean inhaled corticosteroid (ICS) 884 microg.day(-1)) were randomised to budesonide/formoterol 160/4.5 microg two inhalations b.i.d. plus additional inhalations as needed, or salmeterol/fluticasone 50/250 microg b.i.d. plus salbutamol as needed. Treatment was prescribed open label; after 4 weeks, physicians could titrate maintenance doses in accordance with normal clinical practice. Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation versus salmeterol/fluticasone (25% risk reduction). The total number of severe exacerbations was significantly reduced in the budesonide/formoterol group (255 versus 329). Both regimens provided sustained improvements in symptoms, as-needed use, quality of life and FEV1, with differences in favour of the budesonide/formoterol group for as-needed use (0.58 versus 0.93 inhalations.day(-1)) and FEV1 (post-beta2-agonist values). Mean ICS dose during treatment was similar in both groups (653 microg budesonide.day(-1) (maintenance plus as-needed) versus 583 microg fluticasone.day(-1)). The simplified strategy using budesonide/formoterol for maintenance and reliever therapy is feasible, safe and at least as effective as salmeterol/fluticasone plus salbutamol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Internationality; Male; Middle Aged; Patient Satisfaction; Prevalence; Prognosis; Quality of Life; Risk Assessment; Risk Factors; Salmeterol Xinafoate; Treatment Outcome

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler or Turbuhaler dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; Vital Capacity

The role of inhaled corticosteroids in the treatment of acute asthma remains a controversial subject.. A randomized, double-blind, placebo-controlled parallel-group clinical trial on the effect of a 5-d course of nebulized budesonide treatment in children with mild to moderate exacerbation of asthma was performed. The need for systemic corticosteroid intervention was evaluated as the primary outcome measure.. Sixty-seven children aged 6 to 15 y were enrolled. During the emergency department phase, they received three nebulizations of either budesonide(1 mg/dose) or placebo, and then in the home phase of the study, they continued their study medications twice a day for another 4 d. Though the level of improvement in the emergency department phase was similar between the groups given either budesonide or placebo treatments (6.8 +/-1.9% vs 4.0+/-1.5%, p = 0.30, respectively), nebulized budesonide caused a trend towards a benefit in terms of the need for systemic corticosteroid intervention (2/33 vs 7/34, p = 0.07), but not in secondary outcome measures.. Though we show a tendency towards a benefit with nebulized budesonide in children with mild to moderate exacerbations in terms of prevention of progression of the illness, the documented benefit is small and includes, at least, consideration for clinical significance, cost-effectiveness, impracticality and safety.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Probability; Recurrence; Reference Values; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Treatment Outcome

Dissatisfaction with medication may negatively affect compliance and thus the effectiveness of the treatment. However, no prospective well-controlled studies have assessed the relative patient satisfaction with competing inhaled corticosteroids in a real-life setting. The objective of the current study was to compare the relative patient satisfaction with budesonide inhalation powder administered via Turbuhaler (AstraZeneca LP, Wilmington, DE) (200 to 1600 microg/d using one of 3 dosing strengths: 100, 200, or 400 microg per inhalation) and triamcinolone acetonide administered via pressurized metered-dose inhaler (200 to 1600 microg/d) among persons treated in managed care settings. A total of 945 subjects 18 years of age or older diagnosed with asthma and enrolled in 25 managed care organizations participated in this prospective, randomized, open-label, parallel-group, 12-month study. As part of the study, subjects completed a self-administered, 17-item patient satisfaction questionnaire that addressed 4 domains: side effects, knowledge/ease of use, convenience, and overall satisfaction. Questionnaire reliability was assessed using Cronbach's alpha, and validity was examined by correlating subscale scores with symptom-free days and Medical Outcomes Study 36-Item Short-Form questionnaire and Asthma Quality of Life Questionnaire scores. The satisfaction questionnaire also included a previously validated section addressing patient compliance. Patients receiving budesonide had significantly higher scores for all four satisfaction subscales throughout the study period than did those receiving triamcinolone acetonide. Similarly, compliance scores were consistently higher for the budesonide group. The difference between the treatment groups in overall satisfaction scores at the end of the study was clinically meaningful. Patients treated with budesonide were significantly more satisfied and compliant with their inhaled corticosteroid regimen compared with patients treated with triamcinolone acetonide.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Female; Humans; Managed Care Programs; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Patient Satisfaction; Prospective Studies; Treatment Outcome; Triamcinolone Acetonide; United States

In order to affect the natural course of childhood wheezing and asthma, anti-inflammatory therapy is often prescribed for young wheezing children, but there is lack of long-term follow-up data.. Eighty-two of the original 100 children, hospitalized for wheezing under the age of 2 years in 1992-1993, were re-examined at school age in 1999. The children had participated in an open, randomized, parallel-group trial including a 4-month intervention with inhaled sodium cromoglycate (SCG) or budesonide (BUD). The baseline data, including data on atopy, eosinophilia and viral etiology, were prospectively collected on admission.. At early school age (median 7.2 years), asthma was present in 33 (40%) children. There was less asthma in the original SCG (21%) than in the control group (54%) (OR 0.23; 95% CI 0.07-0.77). The figure was 46% in the BUD group. When the analyses were performed separately for atopic and non-atopic infants, the difference was significant only among atopics. The lowered risk for asthma in the SCG group remained significant in the multivariate logistic regression analysis when adjusted for age, sex and atopy, and further when adjusted for earlier episodes of wheezing and respiratory syncytial virus identification. However, after adjustment for blood eosinophilia, the significance was lost, albeit the risk for asthma remained low (OR 0.21; 95% CI 0.04-1.12). A sensitivity analysis, which was done by including the six drop-outs of the SCG group as unfavorable and the 12 drop-outs of other groups as favorable outcomes in the model, did not change the direction of the result (OR 0.70; 95% CI 0.26-1.89).. An early SCG intervention in infants hospitalized for wheezing was associated with a lowered risk for early school-age asthma, especially in infants with evidence of atopy.

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Cromolyn Sodium; Follow-Up Studies; Humans; Infant; Respiratory Sounds; Treatment Outcome

The efficacy of ciclesonide 160 mug QD (given either in the morning or evening) was compared with budesonide 200 mug BID in adults with stable asthma that was pretreated with inhaled corticosteroids.. This was a randomized, 3-arm, parallel-group study comparing ciclesonide (given in a double-blind, double-dummy regimen) with open-label budesonide. After 2 to 2.5 weeks, during which patients were treated with budesonide 200 microg BID, patients (n = 405) were randomly assigned to receive ciclesonide 160 microg QD AM or 160 microg QD pm, or budesonide 200 microg BID (all administered by metered-dose inhaler) for 12 weeks. All patients received 2 puffs of medication (or placebo) in the morning and evening. The primary efficacy variable was the difference in spirometric forced expiratory volume in 1 second (FEV(1) in liters) from randomization to study end. Secondary efficacy end points were forced vital capacity, peak expiratory flow by spirometry, and diary assessments of peak expiratory flow, asthma symptoms, and rescue medication use. Adverse events were assessed by patient report, investigator observation, physical examination, and laboratory testing; events were classified as mild, moderate, or severe.. Baseline demographic characteristics with regard to sex, age, weight, smoking status, baseline medication use, and FEV(1) were balanced among the treatment groups. Over the course of treatment, both ciclesonide and budesonide maintained FEV(1) compared with baseline. Both ciclesonide regimens were as effective as budesonide 200 microg BID in maintaining FEV(1) during the treatment period versus baseline (ciclesonide 160 microg QD am: 95% CI, -0.120 to 0.045 vs budesonide; P = NS; ciclesonide 160 microg QD pm: 95% CI, -0.061 to 0.105 vs budesonide; P = NS). Ciclesonide 160 microg QD (morning or evening) was comparable with budesonide 200 microg BID for maintaining pulmonary function, asthma symptom scores, and rescue medication use. The incidence of adverse events was not significantly different among the treatment groups, and most adverse events were not related to study medication.. In this study, ciclesonide 160 microg QDwas as effective as budesonide 200 microg BID (400 microg total daily dose) in these adults with persistent asthma. Both treatments were well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Flow Rates; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking.. To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo.. In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients).. Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes.. Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

Topics: Abortion, Spontaneous; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Congenital Abnormalities; Female; Humans; Middle Aged; Pregnancy; Pregnancy Outcome

Otitis media with effusion (OME) is a common pediatric disease and there is great controversy concerning its management. Mechanical, medical and surgical treatments have not proven adequate in resolving the disease and serve mainly to manage complications. Leukotriene inhibitors are new drugs that have been approved recently for the treatment of asthma in children. The aim of this study was to evaluate the impact of leukotriene inhibitor therapy for asthma on the clinical course of OME in children with co-existing disease. Fifty children with bilateral OME and asthma, divided equally into two groups, were studied. The children in the first group were treated with budesonide and terbutaline inhalers together with the leukotriene inhibitor montelukast, whereas the children in the second group were treated with the inhalers alone. Duration of treatment was 30 days. Pneumatic otoscopy, tympanometry and pure-tone audiometry were performed at the beginning and at the end of treatment. Fifteen (60%) of the children receiving inhalers and montelukast and nine (36%) of those receiving only inhalers were found free of OME after 30 days of therapy. Thus, it may be concluded that a statistically significant beneficial effect on the clinical course of OME resulted from the addition of montelukast to the treatment of children with co-existing asthma and OME. Given that no medication has been shown to be effective in OME therapy, further investigation of the possible effects of leukotriene inhibitors is warranted.

Topics: Acetates; Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Otitis Media with Effusion; Quinolines; Sulfides; Terbutaline

Sputum induction with nebulized hypertonic saline is increasingly being used to evaluate airway inflammation. We investigated the procedure-associated risk in 16 asthmatics that were still symptomatic despite on high doses of regular corticosteroid (CS) therapy (7 on daily inhaled CS > or = 800 microg budesonide or equivalent; 9 on additional daily oral CS) and their sputum cellular profile. For comparison, 12 mild stable asthmatics and 10 normal healthy subjects were included. All subjects inhaled 3%, 4% and 5% hypertonic saline sequentially via ultrasonic nebulizer as a means to induce sputum. Maximal percentage fall of Forced Expiratory Volume on One Second (FEV1) during sputum induction was significantly greater in CS-dependent asthmatics (median % [IQR]: 16.0 [11.0-32.3]) than in mild asthmatics (5.3 [4.2-10.8], p = 0.002] and in normal subjects (4.6 [3.4-6.4]), p = 0.0001). The maximal percentage FEV1 fall was inversely correlated with baseline FEV1 (Rs= -0.69; p < 0.0001). Compared to mild asthmatics, induced sputum from CS-dependant asthmatics had proportionately fewer eosinophils (2.2 [0.8-7.0] versus 23.3% [10.7-46.3], p = 0.003) and greater neutrophils (64.2 [43.9-81.2] versus 28.7 [19.0-42.6], p = 0.009). Sputum neutrophils showed a significant inverse correlation to FEV1 (Rs = -0.51, p = 0.01). We concluded that sputum induction using nebulized hypertonic saline should be performed with caution in CS-dependant asthmatics. The airway cellular profile observed suggests that the immunopathology underlying CS-dependant asthmatics may be different or a consequence of CS therapy.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Saline Solution, Hypertonic; Sputum

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Chemistry, Pharmaceutical; Cross-Over Studies; Female; Half-Life; Humans; Male; Nebulizers and Vaporizers

Inhaled corticosteroids are widely used to treat asthma. There is a need to be able to compare different inhaled corticosteroids and different doses of an inhaled corticosteroid to determine potency and dose equivalence, but measuring efficacy in a dose related manner is difficult because of their slow onset of action. There is uncertainty about the role of sequential dosing regimens and the best end point for such studies. We have explored the use of sequential quadrupling dose regimens and a range of end points to assess the response to budesonide in subjects with asthma.. 21 subjects with mild asthma, aged 18-65, took part in a randomised three way crossover study comparing two sequential and one non-sequential regimen, separated by at least 3 weeks. The sequential regimens consisted of increasing doses of inhaled budesonide (100, 400 1600 microg/day) with each dose being given for 1 or 2 weeks; the non-sequential regimen consisted of 1600 microg/day for 2 weeks with end points measured after 1 and 2 weeks. The end points studied included the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP), lung function, symptoms, and bronchodilator use.. There was a dose related increase in PD20AMP with both sequential dose regimens. The increase in PD20AMP ranged from 1.49 doubling doses (DD) following the lowest dose (100 microg/day) to 3.1 DD following the highest dose (1600 microg/day) in the 1 week sequential regimen and from 1.98 to 4.03 DD in the 2 week sequential regimen; standard deviations (SD) for the changes in PD20AMP ranged from 1.3 to 2.6 DD. Changes in forced expiratory volume in 1 second (FEV1) and morning peak expiratory flow rate (PEFR) were dose related but small and more variable (maximum change in FEV1=148 ml, SD 228 ml), while changes in evening PEFR, symptoms, and bronchodilator use were small and not dose related. Change in PD20AMP after budesonide 1600 microg did not differ significantly between regimens.. Combining PD20AMP measurements with a sequential regimen of three quadrupling doses of an inhaled corticosteroid given for 1 or 2 weeks provides clear dose-response curves for comparative studies. PD20AMP is a more sensitive end point for this purpose than FEV1, PEFR, symptoms, or relief inhaler use.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Single-Blind Method

It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP).. Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action.. There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments.. PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Time Factors; Treatment Outcome

The efficacy of different facemasks that can be used in the delivery of aerosol medication to children with recurrent wheeze or asthma was investigated. The results showed a statistically significant difference between some of the masks used, which has important implications for current clinical practice

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Humans; Infant; Masks; Respiratory Sounds

The currently available facemask interface for the Nebuchamber (N) valved-holding chamber (VHC) provides a very poor seal to the face, which, on average, decreases the aerosol dose and was previously shown to increase the variability of aerosol delivery. The efficiency of a redesigned mask (RD) for the Nebuchamber with a potentially better seal was compared to the standard mask (SM) supplied with the N in a randomized real-life crossover clinical trial. Twenty children (mean age, 26 +/- 10 months) were randomized to use the Nebuchamber for 1 week with the old mask and then for another week with the newer mask, and vice versa. Filters, changed daily, inserted between the mask and the VHC, trapped the delivered drug (budesonide). The dose of budesonide was quantified by high-performance liquid chromatography (HPLC). Use of the redesigned mask improved aerosol delivery to the filter by 30%, compared to the SM (mean 28.1 +/- 7.7% of nominal dose with RD vs. 21.6 +/- 9.6% with SM, P = 0.017). The relatively high within-subject variability in aerosol delivery (36-38%) did not change, however. Facemasks are arguably the most important determinants of aerosol delivery. The newly developed RD for the Nebuchamber proved to be considerably more efficient than the SM for aerosol delivery to young children. Patient-related factors may be more important with respect to the variability observed.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Equipment Design; Female; Humans; Infant; Male; Masks; Nebulizers and Vaporizers; Patient Satisfaction

Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress.. The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity.. EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children.. In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01).. Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Cysteine; Dinoprost; F2-Isoprostanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotrienes; Male; Nitric Oxide; Oxidative Stress; Severity of Illness Index

Ciclesonide is an inhaled corticosteroid (delivered via a hydrofluoroalkane metered-dose inhaler) that is converted to an active metabolite, desisobutyryl-ciclesonide, in the lung, thereby minimising effects on endogenous cortisol. In two 12-week, randomised studies in patients with asthma, ciclesonide 80 or 320 microg once daily was at least as effective as budesonide 400 microg/day at increasing forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline; ciclesonide 320 microg daily was significantly more effective than budesonide 400 microg once daily in one study. In a randomised, double-blind study in patients with asthma controlled with high-dosages of inhaled corticosteroids, FEV(1) and FVC decreased significantly from baseline at 12 weeks in patients receiving ciclesonide 320 microg daily or budesonide 400 microg daily; peak expiratory flow values decreased significantly only in patients receiving budesonide. Inhaled ciclesonide 80 or 320 microg daily improved asthma symptom scores and decreased the use of rescue medication by a similar, significant amount to budesonide 400 microg/day in two 12-week studies. Inhaled ciclesonide was generally well tolerated in patients with asthma. Ciclesonide did not suppress biochemical markers of adrenal function in 52-week studies. The long-term (>52 weeks) systemic effects of ciclesonide remain unknown.

Topics: Administration, Inhalation; Adult; Asthma; Budesonide; Drug Administration Schedule; Esterases; Half-Life; Humans; Injections, Intravenous; Metered Dose Inhalers; Pregnenediones; Time Factors

Clinical studies have demonstrated the efficacy and relative safety of inhaled corticosteroids in the treatment of asthma. However, effectiveness and cost-effectiveness comparisons of available inhaled corticosteroids in real-life clinical settings are lacking.. This study compared the effectiveness and safety of budesonide administered via dry-powder inhaler versus that of triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adult patients with persistent asthma treated in a managed care setting.. This was a randomized, open-labe, 52-week study of adult patients (aged >or= 18 years) with persistent asthma enrolled in 25 US health plans. The primary study outcome was mean change from baseline to the end of treatment in symptom-free days. Secondary variables were changes from baseline in number of episode-free days, episode-free days at 52 weeks, forced expiratory volume in 1 second (FEV(1)), forced vital capacity, asthma symptom scores, breakthrough bronchdilator use, patient discontinuations, and health-related quality of life. Patients were issued diaries in which to record use of study medication and concomitant asthma medication use, as well as daytime and nighttime asthma symptom severity. Patients were assessed at weeks 4, 13, 26, 39, and 52. Safety was assessed based on adverse events and changes in laboratory tests, vital signs, and physical examinations.. A total of 945 patients (344 men, 601 women; mean [SD] age, 46.8 [14] years) were enrolled; 631 received budesonide and 314 received triacinolane acetonide. Improvements in all effectiveness variables were observed with both treatments. The mean increase from baseline in the number of symptom-free days per month assessed at month 12 was 7.74 (95% CI, 6.81-8.66) for patients receiving budesonide and 3.78 (95% CI, 2.47-5.09) for patients receiving triamcinoline acetonide ( P<0.001). The estimated annual mean (SD) number symptom-free days for patients receiving budesonide was 141.1 (125.0) over the treatment phase, compared with 99.3 (112.1) for those receiving triamcinolone acetonide (P<0.001). Patients receiving budesonide demonstrated significant improvements (compared with those receiving triamcinolone acetonide) in overall quality of life, daytime and nighttime asthma symptom severity, breakthrough bronchodilator use, and FEV(1) (all P<0.001). Safety measures were similar between groups.. In these managed care settings, budesonide inhalation powder administered via dry-powder inhaler was significantly more effective than triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adults with persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Managed Care Programs; Middle Aged; Nebulizers and Vaporizers; Quality of Life; Triamcinolone

Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms.. This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens.. Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW).. The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011).. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Analysis of Variance; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Costs; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Ventilation; Salmeterol Xinafoate

We investigated the changes in renal excretion of calcium, sodium, and potassium in asthmatic children treated with inhaled budesonide, an inhaled glucocorticoid. Twenty-two asthmatic patients (7 female, 15 male, mean age 10.1+/-4.3 years) treated with 400-600 microg/day inhaled budesonide and 23 healthy children (6 female, 17 male, mean age 10.2+/-2.8 years) were enrolled in the study. The parameters recorded were serum sodium, potassium, calcium, phosphorus, alkaline phosphatase (ALP), type I collagen carboxyterminal telopeptide (ICTP), osteocalcin, intact parathyroid hormone (PTH) levels, first spot morning urine calcium/creatinine ratio, sodium/potassium ratio, and daily renal calcium excretion rate (UCa-ER). These parameters were measured in the control group and pre- and post-budesonide treatment in asthmatic children. Serum electrolytes, ALP, PTH, ICTP, and UCa-ER were in the normal ranges and were not significantly different between controls and asthmatic children. Serum levels of ICTP increased, while levels of osteocalcin decreased after budesonide therapy in the asthmatic group ( P=0.001, P=0.005). UCa-ER was decreased after budesonide therapy in asthmatics ( P=0.000). In conclusion, moderate doses of inhaled budesonide cause hypocalciuria and decreased bone turnover. These results may be attributed to a mechanism compensating for decreased absorption of calcium in the gut due to the topical effect of swallowed budesonide rather than the systemic effects of the drug. Increased bone metabolism and decreased turnover may have an important role in this compensatory mechanism.

Topics: Administration, Inhalation; Alkaline Phosphatase; Asthma; Biomarkers; Bone and Bones; Bronchodilator Agents; Budesonide; Calcium; Child; Collagen Type I; Female; Humans; Male; Parathyroid Hormone; Potassium; Sodium

The aim of this pilot study was to compare a the HaloLite Paediatric Nebulizer (HPN) with a pressurized metered dose inhaler and valved holding chamber (pMDI VHC, Aerochamber) in terms of drug delivery, adherence to treatment, compliance with device, true adherence, and acceptability. Fourteen children aged 11-36 months with asthma on regular treatment with inhaled corticosteroids were enrolled into an open, randomized, crossover trial. They received budesonide for 2 weeks with each delivery system. Both devices incorporated a datalogger which recorded information on how the device was used. The HPN was preprogrammed to deliver 25 microg of budesonide to the patient. A single actuation of budesonide 200 microg was used with the pMDI VHC. The median delivered dose of budesonide was 36 microg (range, 31-45 microg; CV, 15%) for the HPN and 53 microg (range, 17-85 microg; CV, 47%) for the pMDI VHC. The median adherence was 68% (range, 11-96%) with the HPN and 71% (range, 11-100%) with the pMDI VHC. The median device compliance was 30% and 51% and the median true adherence was 23% and 36%, respectively. The shape, size, and weight of the HaloLite Paediatric Nebulizer were generally less acceptable than the shape, size, and weight of the pMDI VHC with datalogger. These results indicate that reproducible quantities of drug can be delivered to very young children using AAD technology such as that incorporated into the HPN. Drug delivery with the pMDI VHC was more variable, but parents preferred this device.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Equipment Design; Female; Humans; Infant; Male; Metered Dose Inhalers; Nebulizers and Vaporizers; Parents; Patient Compliance; Pilot Projects; Surveys and Questionnaires; United Kingdom

The aim of this study was to compare the clinical efficacy, safety, and acceptability of budesonide inhaled from Easyhaler dry powder inhaler (DPI) (Giona Easyhaler, Orion Pharma, Finland) and from Turbuhaler DPI (Pulmicort Turbuhaler, AstraZeneca, Sweden) in the treatment of asthma in children. The 6-month, randomised, double-blind, double-dummy, parallel-group study was conducted in 229 completed, asthmatic children (5-10 years), who were symptomatic at study entry. For the first 2 months, children inhaled budesonide 2 x 200 microg b.i.d. (high-dose treatment period). Thereafter, the daily dose of inhaled budesonide was 2 x 100 microg for 4 months (low-dose treatment period). The study was carried out at 32 centers in Finland, Sweden, Norway, and Denmark. During the high-dose treatment period, the initially symptomatic patients improved in both treatment groups and the achieved control was maintained during the low-dose treatment period. An improvement was seen in the efficacy outcome parameters in the initially symptomatic patients in both treatment groups. Also, there were no differences in the number of asthma exacerbations between the treatments. The urinary free cortisol/creatinine (UCC) ratios were significantly lower in the Turbuhaler group compared to the Easyhaler group after the high-dose treatment period. In addition, there was a slight but statistically significant slower growth rate in the Turbuhaler group after the 6- month treatment period compared with the Easyhaler group. Pulmicort Turbuhaler and Giona Easyhaler are equally effective in the treatment of asthma in children aged 5-10 years old. Budesonide inhaled from Turbuhaler showed slightly greater systemic effects than budesonide inhaled from Easyhaler. The majority of children and parents preferred Easyhaler to Turbuhaler.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Nebulizers and Vaporizers

Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. A randomised, double-blind, double-dummy, single-dose, crossover study included 27 outpatients with asthma (mean age 35 years; mean FEV1 90% predicted normal). Immediately following methacholine-induced bronchoconstriction (fall in FEV1 > or = 30%), patients inhaled budesonide/formoterol (160/4.5 microg, 1 or 2 inhalations; Symbicort Turbuhaler), salmeterol/fluticasone (50/250 microg; Seretide Diskus) or placebo on 4 study days. Lung function and Borg score were assessed for 30 min. During methacholine-induced provocation (final mean FEV1 62.5% of baseline), mean Borg score increased 10-fold (from 0.3 to 3.0 units). Hereafter, mean FEV1 at 3 min improved significantly more after budesonide/formoterol 1 and 2 inhalations (37 and 38%, respectively) than after salmeterol/fluticasone (23%; P < 0.001) or placebo (10%; P < 0.001). Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P < 0.001) and placebo (> 30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P < 0.05) and placebo (-0.23 units; P < 0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Nebulizers and Vaporizers

Supraphysiological doses of exogenous glucocorticosteroids cause adrenocortical suppression. Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant adrenal androgen and estrogen precursor. We studied to what extent inhaled glucocorticosteroid therapy for asthma decreases serum DHEA-S concentrations.. We measured serum DHEA-S and cortisol concentrations in 101 adult patients with newly detected mild asthma before and after 2 and 12 weeks of treatment with inhaled glucocorticosteroids. The patients were randomized to receive budesonide 200 microg/day (low dose group, n=50) or 800 microg/day (high dose group, n=51) in two parallel groups double-blindly.. In the low dose group, serum DHEA-S concentrations decreased from the baseline by a mean of 8 % (95 % confidence interval (CI), 3-13 %, P<0.01) after 2 weeks of therapy, and by 2 % (95 % CI, 9 % decrease to 5 % increase, NS) after 12 weeks. In the high dose group, the respective decreases were 16 % (95 % CI, 10-21 %, P<0.001) and 18 % (95 % CI, 12-24 %, P<0.001). The difference between the treatment groups was significant at both 2 and 12 weeks. During the 12 week treatment period the baseline concentrations of serum cortisol did not decrease in the low dose group, while in the high dose group the decrease was significant at 12 weeks (P<0.01), but not at 2 weeks. The forced expiratory volume in 1 s improved equally well in both groups.. Inhaled budesonide decreased serum DHEA-S concentrations, which may indicate adrenocortical suppression. Reduced adrenal production of androgen and estrogen precursors may increase the risk of osteoporosis especially in postmenopausal women.

Topics: Administration, Inhalation; Adrenal Cortex; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Dehydroepiandrosterone Sulfate; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Osmolar Concentration

Evidence for the anti-inflammatory activity of leukotriene receptor antagonists in humans is somewhat limited. There are also no data comparing the anti-inflammatory effects of leukotriene receptor antagonists with those of inhaled corticosteroids. This study was designed to assess the clinical efficacy and anti-inflammatory effects of leukotriene receptor antagonist plus low-dose inhaled corticosteroids compared to those of a high-dose inhaled corticosteroid in patients with mild-to-moderate asthma.. Forty-nine patients with newly diagnosed asthma were recruited. They were randomly assigned to groups that received, for a 6-week period, either (1) budesonide, 600 microg bid (1,200 microg/d) or (2) budesonide, 200 microg (400 microg/d), and zafirlukast, 20 mg bid. The variables of asthma control were recorded daily. Sputum induction and methacholine provocation tests were performed.. The results indicated that the administration of a low-dose inhaled corticosteroid plus zafirlukast was as effective as that of a high-dose inhaled corticosteroid regarding clinical improvement and anti-inflammatory effects (ie, eosinophil percentage, and eosinophilic cationic protein [ECP] and cysteinyl leukotriene C4 levels in induced sputum). Nineteen (group 1, 8 patients; group 2, 11 patients) of 49 patients (38.8%) had returned to normal airway responsiveness after treatment. Among these patients, 16 patients (84.2%) had normal ECP levels and 10 patients (52.6%) had normal percentages of eosinophils. ECP level, but not the eosinophil percentage, was significantly associated with symptom scores. The peak expiratory flow rate (PEFR) showed a significant correlation with the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) instead of with symptom scores.. The addition of a leukotriene modifier to treatment with low-dose inhaled corticosteroids is equivalent to treatment with high-dose inhaled corticosteroids in patients with newly diagnosed mild-to-moderate asthma. In addition to symptoms and PEFR, the monitoring of ECP and PC20 may be of great value in achieving optimal control of asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Female; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Severity of Illness Index; Sulfonamides; Tosyl Compounds

Patient-guided management of asthma using adjustable dosing of budesonide/formoterol in a single inhaler (Symbicort) was compared with fixed dosing in an open-label, multicentre, randomised study. Patients, uncontrolled on an inhaled corticosteroid (ICS) or controlled on an ICS and a long-acting beta2-agonist, entered a 4-week run-in period and received budesonide/formoterol (80/4.5 or 160/4.5 microg), 2 inhalations b.i.d. Following randomisation, the fixed-dosing group (n = 764) continued this regimen for a further 12 weeks. The adjustable-dosing group (n = 775) could step down to 1 inhalation b.i.d. if symptoms were controlled, and, at early signs of worsening symptoms, promptly step up to 4 inhalations b.i.d. for < or = 2 weeks. During run-in, National Heart, Lung and Blood Institute symptom-severity grading was maintained in 60% and improved in 31% of patients, clinic peak flow increased from 400 to 4191/min (P<0.001), and health-related quality of life (overall MiniAQLQ) improved from 4.6 to 5.4 (P<0.001). Patients effectively used the adjustable-dosing regimen; 79% reduced budesonide/formoterol dosage and, compared with fixed dosing, the number of inhalations were significantly lowered (3.2 vs. 3.8 inhalations/day, P<0.05). Both regimens were well tolerated. In both groups, symptom control was maintained or improved in 85-86% of patients, and 94% experienced no treatment failures. Consistent with current guidelines, adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma control at reduced medication doses.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome

We previously showed that individuals with seasonal allergy have a reduced ability to condition air, which was improved by nasal inflammation. We also showed that subjects with asthma have a reduced ability to condition air. Because individuals with asthma usually have inflammation in the nose, we hypothesized that treatment with an intranasal steroid would reduce nasal inflammation and further decrease nasal conditioning capacity. We performed a randomized, double blind, placebo-controlled, 2-way crossover study on 20 subjects with asthma comparing the effect of treatment with intranasal budesonide for 2 weeks on nasal conditioning. Treatment with budesonide caused no significant effect on nasal conditioning as compared with placebo. When we evaluated the subgroup of nonsmoking subjects, budesonide caused a significant reduction in nasal conditioning. We speculate that nasal inflammation in nonsmoking individuals with asthma increases the conditioning capacity and reducing it with an intranasal steroid worsens the ability of the nose to condition air. In addition, smoking causes an increase in nasal conditioning capacity by non-steroid-dependent factors. These observations help us understand the pathophysiology of nasal conditioning, but do not negate the positive clinical benefits of budesonide on treating nasal inflammation.

Topics: Administration, Intranasal; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Humans; Humidity; Male; Nasal Cavity; Nasal Mucosa; Smoking

To determine the safety of long-term (36 months) administration of an inhaled corticosteroid (budesonide) on hypothalamic-pituitary-adrenal (HPA) axis function in children with mild to moderate asthma.. This was an ancillary study of the Childhood Asthma Management Program (CAMP). Sixty-three children who had mild to moderate asthma and were enrolled in CAMP underwent evaluation of HPA axis function before and 12 and 36 months after receiving continuous therapy with either an inhaled anti-inflammatory agent (budesonide 400 microg/day or nedocromil 16 mg/day) or placebo. HPA axis function was assessed by serum cortisol levels 30 and 60 minutes after 0.25 mg of adrenocorticotrophic hormone (ACTH) and 24-hour urinary free cortisol excretion.. There were no differences in serum cortisol levels after ACTH stimulation between treatment groups, regardless of time after ACTH administration or months of follow-up. Urinary cortisol excretion per body surface area was similar in both treatment groups at 36 months, after adjusting for age at randomization, race, gender, and clinic. Cumulative inhaled corticosteroid exposure did not influence serum cortisol response to ACTH or urinary free cortisol excretion at 36 months.. We found no effects of chronic budesonide treatment at a dose of 400 micro g/day on HPA axis function in children with mild to moderate asthma and demonstrated the absence of a cumulative effect on HPA axis function over a 3-year period.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisone

Exogenous glucocorticoids suppress short-term lower leg growth in children as assessed by knemometry. The knemometric measurements, however, may be confounded by reductions in the thickness of the cutis and subcutis over the knee.. To assess whether inhaled glucocorticoid-induced suppression of short-term growth is accompanied by changes in the thickness of the cutis and subcutis.. The study was a randomized, controlled, crossover trial with 1 wk treatment, run-in and washout periods. Active treatment was inhaled budesonide 200 microg twice daily. Short-term growth was assessed by knemometry, and the thickness of the cutis and subcutis over the knee, on the volar forearm and abdomen was measured by 20 MHz B-mode ultrasound.. Nineteen children with asthma aged 7 to 13 y.. Lower leg growth was significantly reduced during budesonide treatment (0.27 mm/wk) compared to the treatment-free period (0.54 mm/wk) (p = 0.02, 95%: -0.50 to -0.05). Variations in the thickness of the cutis were seen during budesonide treatment (mean +/- SEM): -0.01 +/- 0.03 mm over the knee, -0.02 +/- 0.02 mm on the forearm and 0.01 +/- 0.02 mm on the abdomen. The variations in the total thickness of the cutis and subcutis were -0.05 +/- 0.12 mm, 0.06 +/- 0.12 mm and -0.06 +/- 0.10 mm during budesonide treatment. The variations in thickness of the cutis or subcutis were not statistically different during budesonide treatment and the treatment free period in any anatomical location.. Short-term lower leg growth suppression induced by inhaled glucocorticoids is not confounded by variations in thickness of cutis or subcutis. The present observations further establishes knemometry as a reliable tool for assessment of the risk of growth suppression of inhaled glucocorticoids in children with asthma.

Topics: Abdomen; Administration, Inhalation; Adolescent; Asthma; Budesonide; Child; Cross-Over Studies; Female; Forearm; Glucocorticoids; Growth; Humans; Knee; Leg; Male

Although current guidelines suggest the use of inhaled corticosteroids as the first line therapy in persistent asthma, the concerns about high-dose corticosteroids may limit their usage. We aimed to investigate the efficacy of inhaled budesonide plus oral montelukast versus a double dose of inhaled budesonide.. Thirty patients with moderate asthma took part in the study. Following a 2-week run in period, the patients were randomized into two groups to receive 400 microg/day of inhaled budesonide plus 10 mg/day of montelukast (BUD + M group) or 800 microg/day of inhaled budesonide (high BUD group). The patients were evaluated at 2-week intervals (during a total treatment period of 6 weeks) for symptom scores, asthma exacerbations, lung function, use of short-acting beta2 agonist, blood eosinophil counts and adverse events.. At the end of the study, morning and daytime symptom scores were significantly reduced within the groups. Although there was a significant decrease in the frequency of short-acting beta2 agonist use in the BUD + M group, the decrease in the high BUD group was not significant. During the study period, no patient in either group experienced an asthma exacerbation. Blood eosinophil levels significantly declined in both the BUD + M (0.87 +/- 0.31%) and high BUD groups (0.67 +/- 0.29%) as compared with baseline levels (BUD + M = 2.60 +/- 0.65%, high BUD group = 2.60 +/- 0.47%; P < 0.05).. Our results suggest that the addition of montelukast to low-dose inhaled budesonide is as effective as a double dose of inhaled budesonide in asthma control.

Topics: Acetates; Adult; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists; Male; Quinolines; Spirometry; Sulfides

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS). Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7-16 yrs), who inhaled 0.2 mg salbutamol t.i.d. and 0.2 mg budesonide t.i.d. (beta2-agonist (BA)+ICS), or placebo (PL) t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children. Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL. Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Humans; Longitudinal Studies; Lung; Male; Respiratory Function Tests; Treatment Outcome

Asthma guidelines suggest a stepwise approach to maintenance pharmacological treatment of persistent asthma until control is attained, and a 3 month review of the fixed maintenance dosing for step-up or step-down adjustment. This 12-week study compared the efficacy and safety of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler 160/4.5 or 80/4.5 microg) given as adjustable maintenance or fixed maintenance dosing. Patients (n = 2358) were randomised to budesonide/formoterol fixed maintenance dosing (two inhalations bid) or adjustable maintenance dosing (two inhalation bid; stepping up to four inhalations bid if asthma worsened for a maximum of 14 days; stepping down to two inhalations once nocte or one inhalation bid if symptoms were controlled) for 12 weeks, following a 4-week run-in period on budesonide/formoterol two inhalations bid. Primary efficacy variables were frequency of asthma exacerbations and changes in patients' asthma symptom severity. Secondary variables were asthma control, safety and health economics. Both adjustable maintenance dosing and fixed maintenance dosing were associated with similar low frequency of exacerbations (5% both groups; ns) and similarly improved lung function, with similarly fewer nocturnal awakenings and less asthma symptoms compared with the mean value of the run-in period. However, patients on adjustable maintenance dosing used 24% fewer study drug compared with fixed maintenance dosing (2.95 versus 3.86 inhalations daily; p < 0.0001) and incurred in a significant (p <0.0001) reduction in total costs (direct+indirect) compared with fixed maintenance dosing. In conclusion, adjustable maintenance dosing with budesonide/formoterol effectively controls asthma at a reduced drug load with lower costs than fixed maintenance dosing.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Nebulizers and Vaporizers; Treatment Outcome

Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma.. Over a 6 month period a cohort of patients were evaluated prospectively and randomised in a double blind controlled trial to treatment with either a continued maintenance dose (MD) of inhaled corticosteroid or doubling the dose (DD) at the time of an exacerbation.. A total of 290 patients were randomised (33% male) and 98 (DD, n = 46) experienced evaluable asthma exacerbations during the study period. Mean (SD) baseline characteristics at randomisation (age 33.5 (14.0) years; forced expiratory volume in 1 second (FEV(1)) 2.8 (0.7) l; peak expiratory flow (PEF) 422.9 (110.5) l/min) were similar in both groups. In the DD group 41% of patients were considered treatment failures because they either required systemic steroids (n = 12), had an unscheduled visit to a physician (n = 1), or their asthma did not return to baseline (n = 6). This did not differ from the MD group in which 40% were treatment failures (n = 9, 0, and 12, respectively; p = 0.94).. In patients who regularly take an inhaled corticosteroid, doubling the maintenance dose may not affect the pattern of the exacerbation.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Treatment Outcome

There are few controlled studies on the effects of anti-inflammatory treatment on airway inflammation in newly diagnosed childhood asthma.. Sixty children with newly diagnosed mild persistent asthma, 5-10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 microg twice daily for 1 month, 200 microg twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three-times daily for 6 months. All exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study.. Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 x 10(9)/l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness (R = -0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma (P < 0.0001), and in children with a history wheezing than in children without wheezing (P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function (P = 0.007), decreased symptoms (P = 0.007) and sputum eosinophils (P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (>3%).. Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement.

Topics: Asthma; Breath Tests; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Cross-Sectional Studies; Eosinophils; Female; Humans; Longitudinal Studies; Male; Nitric Oxide; Sputum

The use of objective outcome measures that assess airway inflammation in pediatric asthma can provide a good evaluation of asthma severity and treatment response. In this double-blind and randomized study the effects of 200 micro g of budesonide and 800 micro g of budesonide on markers of inflammation (exhaled nitric oxide (eNO), eosinophil protein X (EPX) excretion in urine) and on lung function (FEV (1)) were prospectively investigated in 24 ICS-naive children with mild persistent to moderate persistent asthma over a period of eight weeks. After eight weeks of treatment 200 micro g and 800 micro g of budesonide led to a significant decrease (p < 0.025) in eNO [median (90 % interval): 200 micro g: - 17.2 ppb (- 54.6 to 0.9); 800 micro g: - 13.2 ppb (- 44.6 to - 1.7)]. A significant change in urinary EPX excretion was only observed in the high dose group [200 micro g: - 10.3 micro g/mmol creatinine (- 116.2 to 50.5), p = 0.9; 800 micro g: - 49.2 micro g/mmol creatinine (- 231.0 to 48.7), p = 0.02]. However, a significant difference between the change from baseline after 8 weeks of either group was found neither for eNO (p = 0.66) nor for EPX excretion (p = 0.04). In conclusion, our data demonstrate that 800 micro g budesonide per day did not show any advantage in reduction of airway inflammation, measured by eNO and urinary EPX excretion, in children with mild persistent to moderate persistent asthma.

Topics: Adolescent; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Eosinophil-Derived Neurotoxin; Female; Humans; Male; Nitric Oxide; Respiratory Function Tests; Ribonucleases

To review the worldwide safety data for budesonide inhalation suspension (Pulmicort Respules) to provide a budesonide inhalation suspension pediatric tolerability profile.. Clinical study data were obtained from AstraZeneca safety databases used by the US Food and Drug Administration to support the approval of budesonide inhalation suspension and from postmarketing surveillance reports (January 1, 1990, through June 30, 2002).. Completed parallel-group studies of patients with asthma 18 years and younger.. Safety data for budesonide inhalation suspension were pooled from 3 US, 12-week, randomized, double-blind, placebo-controlled studies (n = 1,018); data from their open-label extensions (n = 670) were pooled with data from a fourth US open-label study (n = 335). Data for 333 patients 18 years and younger enrolled in 5 non-US studies also were analyzed. No posterior subcapsular cataracts were reported in any study, and the frequencies of oropharyngeal events and infection with budesonide inhalation suspension were comparable with those of reference treatments. No increased risk of varicella or upper respiratory tract infection was apparent, and budesonide inhalation suspension did not cause significant adrenal suppression in studies assessing this variable. There were small differences in short-term growth velocity between children who received budesonide inhalation suspension and those who received reference treatment in 2 of 5 trials that evaluated this variable. No increased risk of adverse events was apparent from postmarketing reports.. Short- and long-term treatment with budesonide inhalation suspension, using a wide range of doses, is safe and well tolerated in children with asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Bone and Bones; Budesonide; Candidiasis, Oral; Child; Child, Preschool; Double-Blind Method; Growth; Humans; Hypothalamo-Hypophyseal System; Infant; Pituitary-Adrenal System; Respiratory Tract Infections; Suspensions

There is a need for controlled trials among children with asthma to evaluate and compare different markers of inflammation.. Our goal was to investigate the effect of withdrawal of inhaled budesonide on repeated measurements of exhaled NO (ENO), peripheral blood eosinophils (PBE), sputum/NAL/serum-eosinophil cationic protein (ECP), bronchial hyperresponsiveness (BHR) and forced expiratory volume in 1 s (FEV(1)) in children with allergic asthma.. Eighteen asthmatic children were randomly allocated to continue or discontinue use of inhaled budesonide. They were followed up, at six visits for 4 months with regular blood, serum, sputum, and NAL samples. Sixteen age-matched healthy children served as controls.. ENO, PBE, and S-ECP increased significantly in the withdrawal group (p < 0.05) but not in the continuous treatment group. No trend could be observed during the study for markers in sputum or in NAL in either group.. The present data provide evidence for the clinical usefulness of measuring ENO, PBE, and S-ECP and when combined they could help to avoid over- and undertreatment with corticosteroids in the growing child.

Topics: Adolescent; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Child; Eosinophil Cationic Protein; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Nasal Lavage Fluid; Nitric Oxide; Sputum

Budesonide/formoterol in a single inhaler is an effective therapy for asthma. We investigated whether adjustable maintenance dosing with budesonide/formoterol could maintain health-related quality of life (HRQL) and asthma control.. Asthma patients (n = 4025) received budesonide/formoterol (Symbicort 160/4.5 microg) 2 inhalations twice daily (b.i.d.) for 4 weeks during run-in of this open, multicentre study. Patients were randomised to adjustable dosing (budesonide/formoterol 1 inhalation b.i.d.; stepping up to 2 or 4 inhalations bid for 1 week if asthma worsened) or fixed dosing (budesonide/formoterol 2 inhalations b.i.d.), for 12 weeks. Change in HRQL (standardised Asthma Quality of Life Questionnaire, AQLQ[S], score) during randomised treatment was the primary efficacy variable. Secondary variables included asthma control (peak expiratory flow [PEF], symptom-severity score, nocturnal awakenings, reliever-medication use) and study-medication intake.. Clinically significant (> or = 0.5) improvements in AQLQ(S) score (mean 0.73), morning and evening PEF (mean 42.5 and 24.8 L/min, respectively), and symptom-severity score (mean 0.36) were achieved during run-in. The improvements were maintained in both groups although, overall, adjustable-dosing patients took fewer daily inhalations of budesonide/formoterol than fixed-dosing patients (mean 2.63 versus 3.82, p < 0.001).. Adjustable maintenance dosing with budesonide/formoterol maintains HRQL and asthma control as effectively as fixed dosing and is associated with a reduced drug load overall.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Quality of Life; Respiratory Function Tests; Treatment Outcome

The study was undertaken to examine the clinical effectiveness of nebulizer inhalations of budesonide suspension during severe attacks of bronchial asthma (BA) and the possibility of its use versus systemic glucocorticosteroids (GCSs). Sixty-eight patients admitted for a severe attack of BA were examined. The forced expiratory volume per sec (FEV1) was less than 40% and the peak forced expiration rate (PFER) was less than 150 l/min. First-line therapy included inhaled salbutamol (5-10 mg within 1.5-2 hours), oxygen, and intravenous prednisolone (120 mg). Thirty-two patients showed a good response to first-line therapy (a more than 50% increase in FEV1) as compared with the normal values) (Group 1) and 36 patients with concurrent obstructive lung disease (COLD) had an inadequate response (FEV1 was less than 40% of the normal values) was found in 32 patients (Group 2). Then the patients were randomized: 16 patients from Group 1 took budesonide, 4 mg/day, the other 16 received intravenous prednisolone, 120 mg/day. In Group 2, the efficacy of the drug added to therapy with oral prednisolone, 30 mg/day, was evaluated: 18 patients were given budesonide, 4 mg/day, and 18 received placebo. In patients with a good response to primary therapy, positive clinical and functional changes were found on day 6 of treatment. Group 2 patients receiving budesonide showed a significantly (p < 0.05) more marked positive changes in BA symptoms, FEV1, and PFER, which allowed a course of therapy with systemic GCSs to be reduced. Nebulized budesonide may be used instead of systemic GCSs to treat exacerbated BA if there is a good clinical and functional response to first-line broncholytic therapy, which is indicative of successful abatement of bronchospasm. If there is a poor response to first-line therapy in patients with more severe BA concurrent COLD, the early use of budesonide suspension in addition to systemic GCSs may enhance the efficiency of therapy for BA attacks and reduce the volume of systemic steroidal therapy.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Severity of Illness Index

The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess airway inflammation in children, because bronchoscopy and biopsy carry some risk. The Childhood Asthma Management Program (CAMP) study was designed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers.. At the Denver CAMP site, we sought to evaluate the safety of sputum induction, to determine differences in airway inflammation between treatment groups by using induced sputum analysis, and to examine correlations between other biomarkers and sputum eosinophils.. Sputum induction was performed, and exhaled nitric oxide, circulating eosinophil counts, and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout. Spirometry and a methacholine challenge were also performed according to the CAMP protocol.. Ninety of 117 children provided an adequate sputum sample for analysis. In 9 subjects (3 nedocromil and 6 placebo), sputum induction resulted in bronchospasm. These subjects had greater disease severity, as measured by a lower median prebronchodilator FEV 1 percentage predicted (85.0% vs 96.0%; P =.024) and FEV 1 /FVC ratio (70.0% vs 79.0%; P =.0008); greater bronchodilator reversibility (16.5% vs 6.8%; P =.004); higher serum IgE (1390.0 vs 495.0 ng/mL; P =.017) and circulating eosinophil count (757.0 vs 282.0/mm 3; P =.04); greater use of prednisone (1.9 vs 0.9 courses per 100 person-years; P =.05); and greater supplemental inhaled steroid doses (85.3 vs 0 mg; P =.016). At treatment discontinuation, budesonide-treated patients had a lower median (1st, 3rd quartile) sputum percentage eosinophil (SPEos) (0.2% [0%, 1.2%] vs 0.8% [0.2%, 4.6%]; P =.03) compared with those treated with placebo; no significant difference was noted between nedocromil- and placebo-treated patients. Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone (n = 23) during the washout period compared with patients who remained stable (3.6% [0.4%, 6.4%] vs 0.6% [0.2%, 3.2%] SPEos; P =.023). Finally, greater SPEos was associated with atopy, higher bronchodilator reversibility, lower FEV 1 /FVC ratio, higher exhaled nitric oxide levels, circulating eosinophils, sputum and serum eosinophil cationic protein, more prednisone courses during the treatment period, and greater asthma severity.. Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control. However, this procedure still remains a research tool in asthma because of its requirements for technical expertise.

Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Budesonide; Eosinophils; Female; Humans; Inflammation; Leukocyte Count; Male; Nedocromil; Nitric Oxide; Respiratory Function Tests; Sputum; Treatment Outcome

This study evaluated the efficacy and safety of a novel asthma management strategy--budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy)--compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma.. This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years-80 years], mean baseline forced expiratory volume in 1 s [FEV(1)] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 microg/day) received either budesonide (160 microg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 microg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 microg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to < or = 70% of baseline on 2 consecutive days) was the primary outcome variable.. A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy (p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/formoterol single inhaler therapy compared with budesonide (p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group (p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 microg/day vs 640 microg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated.. Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Hospitalization; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests

The severity of asthma varies between individuals and over time. As a result individuals may have marked variation in their need for asthma treatment. Adjustable dosing enables patients to assume greater involvement in managing their own condition.. To compare the costs and effectiveness of fixed dosing of budesonide/formoterol (Symbicort Turbohaler) with adjustable maintenance dosing.. A cost-effectiveness analysis was conducted from the perspective of the UK NHS. Adults with established asthma currently maintained on > or =400 microg per day inhaled corticosteroid were enrolled in 365 primary care centres in the UK. Patients were run-in on 2 inhalations twice daily of budesonide/formoterol 80/4.5 microg or budesonide/formoterol 160/4.5 microg (depending on steroid requirement) for 4 weeks and were then randomised to the Symbicort adjustable maintenance dosing plan (SAMD) (n = 782; budesonide/formoterol 1-4 inhalations twice daily depending on symptoms) or Symbicort fixed dosing (n = 771; 2 inhalations twice daily) for a further 12 weeks. The primary effectiveness variable was clinically meaningful change in quality of life (QoL) assessed by the miniasthma quality of life questionnaire (AQLQ). Secondary effectiveness measures included symptom-free days with no short-acting beta-agonist use. We assessed the costs of study medication, asthma-related concomitant medication, primary care and hospital contacts. Confidence intervals were generated by nonparametric boot-strapping.. Clinically meaningful improvement in QoL during the first 4 weeks was reported by 40.8% of enrolled patients. During the following 12 weeks, a net 1% (95% CI: -4%, 6%) of SAMD patients and 6% (95% CI: 1%, 10%) of fixed dosing patients reported further improvement. Effectiveness parameters did not differ significantly between groups during the study period. Mean daily cost per patient was pound sterling 1.13 (95% CI: pound sterling 1.08, pound sterling 1.18) in the SAMD group and pound sterling 1.31 (95% CI: pound sterling 1.27, pound sterling 1.34) in the fixed dosing. The difference in mean daily cost resulted in an annual per patient cost difference of pound sterling 65.70. Adjustable maintenance dosing with budesonide/formoterol provided equivalent QoL to fixed dosing at significantly lower cost.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Health Care Costs; Humans; Male; Middle Aged; Primary Health Care; Severity of Illness Index; United Kingdom

To evaluate effectiveness and safety of nebulizer therapy (NT) with broncholytics and pulmicort suspension (PS) in patients with a severe exacerbation of bronchial asthma (BA).. 75 patients with a severe BA exacerbation received broncholytic NT with consideration of comorbid pathology and age. Nebulized PS was used as an alternative to systemic glucocorticosteroids (SGCS). NT efficacy was assessed by changes in clinical symptoms, in the peak expiration velocity (PEV) and spirometry parameters. Safety was controlled by 24-h ECG monitoring, pulsoximetry. PS was examined for effect on adrenal cortex, calcium metabolism, oral infection with Candida. Side effects were registered.. Clinical improvement was recorded in all the patients. NT reduced the number of additional inhalations of short-acting beta2-agonists 4-5 times, on the average. In the end of NT there was a 4.66% increase in SaO2 vs the initial value (p = 0.04). PEV and FEV1 increased. Plasm levels of hydrocortisone and its urine excretion did not lower vs initial values.. The results of the study point to efficacy and safety of combined NT with broncholytics and PS in a severe exacerbation of BA.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Bronchospirometry; Budesonide; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Secondary Prevention

The metal NebuChamber valved holding chamber (VHC) has gained wide acceptance among children with asthma. Due to its nonelectrostatic properties and larger volume, the 250-mL, metal NebuChamber delivers a greater mass of aerosol to a filter at the mouth compared with the commonly used 150-mL polypropylene AeroChamber VHC. Such in vitro results have been used to suggest that this may provide increased efficacy with the NebuChamber. No comparative efficacy data exist for preschool children with asthma.. To compare efficiency and preference of metal and plastic spacers in preschool children.. Children with mild-to-moderate persistent asthma received 200 microg of budesonide twice daily by NebuChamber or AeroChamber, both with the mask provided in a randomized, 2-month, crossover trial. Symptom diary cards, beta-agonist use, and preference by children and parents were compared.. Thirty children (mean +/- SD age, 4.3 +/- 0.3 years) completed the study. There was no difference between the AeroChamber and NebuChamber in clinical efficacy outcomes. There was no difference between the AeroChamber and NebuChamber in parents' view of ease of use, design, acceptability by the children, and overall satisfaction.. Despite a greater total dose delivered to the mouth, the NebuChamber appears no more effective than the AeroChamber and it is not preferred by patients or parents. More parents chose to continue to use the NebuChamber after the study.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aerosols; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cross-Over Studies; Drug Therapy, Combination; Equipment Design; Female; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Parents; Patient Acceptance of Health Care; Patient Satisfaction; Polypropylenes; Stainless Steel; Treatment Outcome

Patients with mild asthma may benefit from increasing their inhaled corticosteroid dose, adding a long-acting beta2-agonist, or both. This study assessed the cost-effectiveness of these options. Patients aged > or = 12 years with mild-to-moderate persistent asthma (n = 1272) were randomised to twice-daily, double-blind treatment with budesonide 100 microg, budesonide 100 microg plus formoterol 4.5 microg, budesonide 200 microg, or budesonide 200 microg plus formoterol 4.5 microg for 12 months. Clinical variables included lung function, number of symptom-free days and number of severe exacerbations. Data on medication use, hospitalisation, visits to health professionals and time off work due to asthma were combined with Swedish unit cost data (1999) to estimate the mean annual cost per patient. Budesonide 200 microg plus formoterol 4.5 microg had the greatest efficacy and effectiveness. Budesonide 200 microg plus formoterol 4.5 microg was both more effective and less costly than budesonide 100 microg plus formoterol 4.5 microg, so a cost-effectiveness ratio was not calculated for this comparison. The cost-effectiveness ratio for budesonide 200 microg plus formoterol 4.5 microg compared with budesonide 200 microg alone was SEK 21 per symptom-free days gained. The combination of budesonide and formoterol in mild-to-moderate persistent asthma improved effectiveness at modest additional cost.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Cost of Illness; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Costs; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Health Care Costs; Health Resources; Humans; Middle Aged; Sick Leave

To determine induced sputum cell counts and interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and leukotriene B4 (LTB4) levels as markers of neutrophilic inflammation in moderate persistent asthma, and to evaluate the response to inhaled steroid therapy.. Forty-five moderate asthmatic patients and 10 non-smoker controls were included in this study. All patients received inhaled corticosteroid (800 microg of budesonide) for 12 weeks. Before and after treatment pulmonary function tests were performed, and symptom scores were determined. Blood was drawn for analysis of serum inflammatory markers, and sputum was induced.. Induced sputum cell counts and inflammatory markers were significantly higher in patients with asthma than in the control group. The induced sputum eosinophil counts of 12 patients (26%) were found to be less than 5%, the non-eosinophilic group, and sputum neutrophil counts, IL-8 and TNF-alpha levels were significantly higher than the eosinophilic group (neutrophil, 50+/-14% versus 19+/-10%, p<0.01). In both groups, there was a significant decrease in sputum total cell counts and serum and sputum IL-8, TNF-alpha and LTB4 levels after the treatment. There was no change in sputum neutrophil counts. Although the sputum eosinophil count decreased only in the eosinophilic subjects, there was no significant difference in inflammatory markers between the groups. The symptom scores were significantly improved after treatment, while the improvement did not reach statistical significance on pulmonary function test parameters.. Notably, in chronic asthma there is a subgroup of patients whose predominant inflammatory cells are not eosinophils. Sputum neutrophil counts and neutrophilic inflammatory markers are significantly higher in these patients. In the non-eosinophilic group, inhaled steroid caused an important decrease in inflammatory markers; however, there was no change in the sputum eosinophil and neutrophil counts.

Topics: Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchitis; Budesonide; Eosinophilia; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Sputum

The study compared clinical efficacy and safety of beclomethasone dipropionate (BDP) given at a dose of 400microg in the mornings and evenings and delivered via pressurised metered dose inhaler (pMDI) with budesonide given via a dry-powder, inspiratory flow driven device at a daily dose of 400microg in the evening. The study was conducted as a week screening. 8-week open comparative clinical trial. At the commencement of the therapy, the baseline characteristics of the patients randomised into the two drug groups were comparable. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEF and FEV1) while safety was assessed by adverse event experiences. At the end of the study, 24 patients (12 in each group) were evaluated. Both drugs were effective in reducing asthma symptoms and frequency of beta2-agonist usage, as well as improving the lung function tests (FEV1 and PEF). However, budesonide given via Turbuhaler provided better effects in all parameters. The drugs were well tolerated and no adverse event was noticed in any of the patients. We therefore concluded that budesonide Turbuhaler administered once daily at a dose of 400microg is more efficacious than beclomethasone 400microg twice daily administered via pressurized metered dose inhaler.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Single-Blind Method; Treatment Outcome

Mild persistent asthma is most effectively controlled with inhaled corticosteroids. Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control. The additional effect of a leukotriene receptor antagonist, zafirlukast, was investigated in stable asthma patients under control with inhaled budesonide. We conducted a randomised, double-blind, placebo-controlled, single center trial to investigate the effects of add-on zafirlukast treatment to budesonide, on symptom score, pulmonary function, bronchial responsiveness, and serum levels of eosinophilic cationic protein (ECP) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide. The present study included 21 mild or moderate asthmatic patients (8 males and 13 females), who were stable at least for 6 weeks with inhaled budesonide (400 microg/day). Serum total antioxidant capacity (TAC) and ECP levels were measured, and symptom scoring, spirometry, and bronchial provocation with methacholine were performed. Then, the patients were randomised to use either placebo or oral zafirlukast (40 mg/day) in addition to budesonide for 6 weeks. At the 6th week, symptom scoring, spirometry, and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again. After add-on zafirlukast treatment to budesonide, forced expiratory volume in 1 second (FEV(1)), TAC and ECP values did not change significantly (p > 0.05) but bronchial hyperresponsiveness and symptom score decreased significantly (p = 0.022) compared to baseline. Thus, in stable asthmatic patients, add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness.

Topics: Adolescent; Adult; Antioxidants; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Eosinophil Cationic Protein; Female; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Placebos; Respiratory Function Tests; Sulfonamides; Tosyl Compounds

This prospective, hospital based, descriptive study was designed to compare improvement in quality of life (QOL) score with objective measures of pulmonary function in children with persistent bronchial asthma receiving inhaled corticosteroid (ICS) therapy. QOL score (measured by an indigenous tool), forced expiratory volume in first second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR) and asthma symptom score were measured in 20 newly diagnosed children with persistent asthma- before, during and eight weeks after ICS therapy. There was a significant improvement in all parameters compared at each follow up visit and at termination of the study (p less than 0.05). The magnitude of improvement in QOL was similar to improvement in objective measures of pulmonary function; although these changes were not similar to changes in asthma symptom score. Improvement in QOL score is likely to be a sensitive measurement of functional improvement in asthmatic children on treatment; however subjective sensation of improvement lags behind objective measures.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Child; Female; Humans; India; Lung; Male; Prospective Studies; Quality of Life; Respiratory Function Tests; Spirometry; Surveys and Questionnaires

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 microgday(-1) suspension for nebulization and budesonide (BUD) 750 microg day(-1) given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40.4% and 51.7% in the BDP and BUD groups respectively in the ITT population (P = 0.28), and the mean number of global exacerbations (major plus minor) decreased respectively by -37.5% in the BDP group and -23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 microg day(-1) suspension for nebulization and BUD 750 microgday(-1) administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Treatment Outcome

The responsiveness to inhaled corticosteroid varies among individual asthmatic patients. It is not known, however, whether the effects of corticosteroids on one bodily tissue reflect the response in another in a given individual. The aim was to a assess whether skin vasoconstrictor assay might predict airway and systemic tissue responsiveness to inhaled budesonide in patients with asthma.. Twenty-two patients with mild to moderate persistent asthma previously enrolled in a dose-response study assessing the effects of inhaled budesonide on airway bronchial challenge testing, exhaled nitric oxide and blood cortisol and eosinophil count were recalled for assessment of vasoconstrictor response to topical budesonide. The MacKenzie vasoconstrictor assay was performed by applying tenfold dilutions from 10(-2) g/ml to 10(-8) g/ml budesonide and visually assessing the degree of skin blanching after 18 h at each concentration.. There was a significant overall dose-response effect for the degree of skin blanching at each concentration. There was no significant correlation between the effects on the skin and measures of anti-asthmatic efficacy or systemic effect after 3 weeks of 400 microg/day inhaled budesonide. There was a significant correlation with the overall dose-cutaneous response effect versus the overall dose-response effect with adenosine monophosphate (r=-0.53) but not methacholine bronchial challenge testing or serum cortisol.. It may not be possible to use the McKenzie vasoconstrictor assay to predict which patients are most or least susceptible to inhaled corticosteroids for anti-asthmatic efficacy or systemic adverse effects.

Topics: Administration, Inhalation; Administration, Topical; Adult; Asthma; Blood Cell Count; Bronchial Provocation Tests; Bronchoconstrictor Agents; Budesonide; Dose-Response Relationship, Drug; Eosinophils; Humans; Hydrocortisone; Nitric Oxide; Predictive Value of Tests; Skin; Vasoconstriction

Proinflammatory leukotrienes, which are not completely inhibited by inhaled corticosteroids, may contribute to asthmatic problems [corrected]. A 16 week multicentre, randomised, double blind, controlled study was undertaken to study the efficacy of adding oral montelukast, a leukotriene receptor antagonist, to a constant dose of inhaled budesonide.. A total of 639 patients aged 18-70 years with forced expiratory volume in 1 second (FEV(1)) > or =55% predicted and a minimum predefined level of asthma symptoms during a 2 week placebo run in period were randomised to receive montelukast 10 mg (n=326) or placebo (n=313) once daily for 16 weeks. All patients received a constant dose of budesonide (400-1600 microg/day) by Turbuhaler throughout the study.. Mean FEV(1) at baseline was 81% predicted. The median percentage of asthma exacerbation days was 35% lower (3.1% v 4.8%; p=0.03) and the median percentage of asthma free days was 56% higher (66.1% v 42.3%; p=0.001) in the montelukast group than in the placebo group. Patients receiving concomitant treatment with montelukast had significantly (p<0.05) fewer nocturnal awakenings and significantly (p<0.05) greater improvements in beta agonist use and morning peak expiratory flow rate (PEFR).. For patients with mild airway obstruction and persistent asthma symptoms despite budesonide treatment, concomitant treatment with montelukast significantly improves asthma control.

Topics: Acetates; Administration, Inhalation; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Treatment Outcome

Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.. After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks.. Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.. The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides; Treatment Outcome

All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects.. The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma.. Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI -11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI -1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI -1026 to 1339) pg/ml (p=0.8).. Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.

Topics: Administration, Inhalation; Androstadienes; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Case-Control Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders

Standard therapy of asthma consists of combined, antiinflammatory (steroids) and anti-obstructive (long acting/short acting beta-agonist) treatment via inhalation using two separate or a single inhalation device. Here, we report the results of using Miflonide (Budesonide 400 - 800 microg per day) and Foradil (Formoterol 24 - 48 microg per day) in cases of moderate and severe asthma previously treated insufficiently with another combination therapy. 80 patients with asthma previously treated insufficiently with any other combination therapy of steroid and long acting beta-agonist were included. Instead of their previous therapy all were switched to therapy with Miflonide and Foradil for eight weeks (two office visits at 4 and 8 weeks). Lung function (peak flow [l/min], FEV1 [I], FVC [I], R(tot) [kPa*s/l]) was performed at every visit. Doctors' and patients' estimation of disease severity, physical examination, drug related side-effects and the use of short acting beta-agonist aerosols were registered. Lung function parameters improved significantly compared to the run in phase prior to the change in medication (peak flow: + 18.4 %, FEV 1 : + 10.7 %, FVC: + 6.8 %, R(tot) : -18.0 %). Use of additional short acting inhalative beta-agonists was reduced. Subjectively, patients judged their general condition as improved, effectiveness as greater compared to previous medication and side effects as tolerable. The use of a combination of Miflonide/Foradil lead to an improvement in subjective and objective parameters in asthma patients that had previously been treated with a variety of other antiinflammatory and anti-obstructive therapy regimens. Reasons for this observation are beside change in medication, patients training in asthma therapy, change of application system, and increase of patients compliance.

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Asthma; Body Mass Index; Bronchodilator Agents; Budesonide; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests

Budesonide inhalation powder administered via Turbuhaler (budesonide Turbuhaler, AstraZeneca LP, Wilmington, DE) is proven efficacious and safe in the treatment of mild to severe asthma.. To evaluate the effect of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in adults with mild to moderate asthma.. In this double-blind, parallel-group study, 309 asthmatic patients between 18 and 70 years of age were randomized to receive once-daily treatment with budesonide 200 or 400 microg or placebo for 6 weeks. Patients initially receiving 400 microg budesonide had their dose reduced to 200 microg (400/200-microg group), and patients receiving 200 microg (200/200-microg group) or placebo continued to receive their assigned doses for a 12-week maintenance phase. HRQL was evaluated using the Asthma Quality of Life Questionnaire at randomization, week 6, and week 18.. Compared with placebo, patients initially receiving 400 and 200 microg budesonide Turbuhaler demonstrated significantly greater HRQL scores at week 6 (P < or = 0.001 and P < or = 0.010, respectively) that were maintained at week 18 (P < or = 0.001). Clinically important (> or = 0.5 unit) improvement in Asthma Quality of Life Questionnaire overall at week 18 was demonstrated by 55% and 43% of patients in the 400/200-microg and 200/200-microg budesonide Turbuhaler groups, respectively.. In patients with mild to moderate asthma, once-daily budesonide Turbuhaler 200 and 400 microg demonstrates statistically significant and clinically important improvements in HRQL that can be maintained with a low dose of 200 microg.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Quality of Life

We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10mg daily, (B) budesonide 400 microg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 microg bid and (D) budesonide 800 microg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC(20) values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV(1), PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C (p < 0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments. The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.

Topics: Acetates; Adult; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Bronchi; Bronchial Provocation Tests; Budesonide; Cyclopropanes; Female; Humans; Male; Quinolines; Sulfides; Treatment Outcome

Although inhaled glucocorticosteroids are recommended for persistent asthma, their long-term effect on recent onset, mild, persistent asthma has yet to be established.. We did a randomised, double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids. Patients aged 5-66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications. The daily budesonide dose was 400 microg, or 200 microg for children younger than 11 years. The primary outcome was time to first severe asthma-related event, and analysis was by intention to treat.. 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation; hazard ratio 0.56 (95% CI 0.45-0.71, p<0.0001). Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo. Compared with placebo, budesonide increased postbronchodilator forced expiratory volume in 1 s (FEV1) from baseline by 1.48% (p<0.0001) after 1 year and by 0.88% (p=0.0005) after 3 years (expressed as percent of the predicted value). The corresponding increase in prebronchodilator FEV1 was 2.24% after 1 year and 1.71% after 3 years (p<0.0001 at both timepoints). The effect of treatment on all outcome variables was independent of the baseline lung function (prebronchodilator or postbronchodilator) or baseline medication. In children younger than 11 years, 3-year growth was reduced in the budesonide group by 1.34 cm. The reduction was greatest in the first year of treatment (0.58 cm) than years 2 and 3 (0.43 cm and 0.33 cm, respectively).. Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Body Height; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Long-Term Care; Male; Middle Aged; Nebulizers and Vaporizers

Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Vital Capacity

We examined whether a combination of glucocorticoids and beta-agonists inhaled by asthmatics had an influence on the metabolism of L-arginine, an amino acid involved in the production of urea, creatinine, and NO that is known to play a significant role in asthma. After lung function tests, we assayed nitrates, urea, and creatinine and determined urinary osmolality in urine samples taken from groups of 129 children (10+/-3 years old) with mild-to-moderate asthma treated with different regimens of drugs. No significant differences in urinary urea levels were noted between the groups. On the other hand, the children treated by the combination of glucocorticoid and beta-agonist (n = 52) had a higher level of urinary creatinine (+40%, P < .001, and a higher creatinine/urea ratio (C/U) expressed as % mass= 5.98 +/- 2.44, P < .001) than did the untreated children (n = 43, C/U = 4.03 +/- 1.24), those treated with glucocorticoid (n = 23, C/U = 4.01 +/- 1.32) or beta-agonist alone (n = 11, C/U = 4.09 +/- 1.01) or control children of the same age (n = 20, C/U = 4.81 +/- .90). Children treated with beta-agonist alone had the lowest mean levels of urinary nitrates (P < .05). The children in group 1 whose C/U ratio was above 6 (n = 24) had a higher FVC (P < .02) and FEV1 (not significant (NS)). However, an overly high C/U may also be indicative of a deleterious influence on the biosynthesis of NO from arginine. Further investigations will be required to determine whether there is a relationship between C/U ratios and lung function parameters, and whether the urinary C/U ratio could be employed as a simple and noninvasive parameter for assessment of treatment in asthmatics.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Creatinine; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Nitrates; Osmolar Concentration; Salmeterol Xinafoate; Terbutaline; Urea

Patients with asthma are a target group for medication with beta2-agonists, often in combination with corticosteroids. Salbutamol is commonly marketed as racemate. R-Salbutamol carries beta2-agonistic property whereas S-salbutamol does not. The racemate undergoes stereoselective sulphatisation by sulfotransferases mainly in the gut and liver, so that S-salbutamol rests for a longer time in the body and reaches higher plasma levels than R-salbutamol. Ten patients with mild stable asthma and at present without cortisone medication were given racemic salbutamol as ventoline 4 mg orally. Plasma and urine levels were estimated until 24 hr after ingestion. For comparison healthy volunteers were treated in the same way. The group of asthma patients was then treated with budesonide inhalations 800 microg daily for one week and the initial programme resumed. Non-cortisone-treated asthmatic patients displayed higher levels of both R- and S-salbutamol in plasma than did healthy volunteers after one single ingestion of racemic salbutamol (CMAX both comparisons P<0.05). Plasma levels of salbutamol isomers in cortisone-treated asthmatic patients resembled the levels in volunteers. The most plausible explanation for the discrepancy in values between asthmatic patients and volunteers is a defective metabolic function by asthmatic patients possibly enzymatic in origin.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Anti-Inflammatory Agents; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Chromatography, High Pressure Liquid; Cortisone; Drug Interactions; Female; Humans; Male; Middle Aged; Stereoisomerism

Previous adult studies demonstrated the clinical efficacy of an additional treatment with leukotriene receptor antagonists on steroid-dependent asthma, but there is little knowledge about anti-inflammatory add-on effects within the lung. In this study, we hypothesized that steroid-treated children exhibit a decrease in bronchial inflammation in induced sputum under additional treatment with montelukast. Twenty-five asthmatic children aged 6 to 14 y, who had been taking inhaled corticosteroids (400-800 microg/d budesonide) regularly for at least 12 wk, were randomized to receive additional treatment with either montelukast (5 mg orally, once daily) or placebo over a 4-wk period. As primary efficacy variable, eosinophil cationic protein (ECP) in induced sputum as direct measurement of bronchial inflammation was assessed before and after treatment. To assure a baseline level of inflammation, an ECP concentration above 100 microg/L was required. Sputum eosinophil count, concentration of exhaled nitric oxide, urinary excretion of eosinophil protein X, and quality-of-life items were considered as secondary outcome variables. After treatment with montelukast, ECP in sputum was significantly reduced (montelukast: median -975 microg/L [5 to 95% confidence interval: -4295 to 583 microg/L]; placebo: 561 microg/L [-1335 to 3320 microg/L]; p < 0.01) and the quality-of-life score had significantly improved (p < 0.05) compared with placebo. Partly explained by low baseline levels, no statistically significant change in concentration of exhaled nitric oxide (p > 0.05), urinary excretion of eosinophil protein X (p > 0.05), or eosinophil count (p > 0.05) was found. In conclusion, add-on treatment with montelukast can suppress sputum ECP in children with steroid-dependent asthma, while at the same time an improvement in quality of life items occurs.

Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Blood Proteins; Budesonide; Child; Cyclopropanes; Drug Therapy, Combination; Eosinophil Granule Proteins; Eosinophils; Female; Humans; Male; Quinolines; Ribonucleases; Sputum; Sulfides; Treatment Outcome

We evaluated the efficacy and safety of low-dose budesonide/formoterol, 80 micro g/4.5 micro g, bid in a single inhaler (Symbicort Turbuhaler; AstraZeneca; Lund, Sweden) compared with an increased dose of budesonide, 200 micro g bid, in adult patients with mild-to-moderate asthma not fully controlled on low doses of inhaled corticosteroid alone.. All patients received budesonide, 100 micro g bid, during a 2-week run-in period. At the end of the run-in phase, 467 patients with a mean FEV(1) of 82% predicted received 12 weeks of treatment with budesonide/formoterol in a single inhaler or budesonide alone in a higher dose. Patients kept daily records of their morning and evening peak expiratory flow (PEF), nighttime and daytime symptom scores, and use of reliever medication.. The increase in mean morning PEF-the primary efficacy measure-was significantly higher for budesonide/formoterol compared with budesonide alone (16.5 L/min vs 7.3 L/min, p = 0.002). Similarly, evening PEF was significantly greater in the budesonide/formoterol group (p < 0.001). In addition, the percentage of symptom-free days and asthma-control days (p = 0.007 and p = 0.002, respectively) were significantly improved in the budesonide/formoterol group. Budesonide/formoterol decreased the relative risk of an asthma exacerbation by 26% (p = 0.02) compared with budesonide alone. Adverse events were comparable between the two treatment groups.. This study shows that in adult patients whose mild-to-moderate asthma is not fully controlled on low doses of inhaled corticosteroids, single-inhaler therapy with budesonide and formoterol provides greater improvements in asthma control than increasing the maintenance dose of inhaled corticosteroid.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

This randomised, double-blind, double-dummy, crossover, placebo-controlled study assessed the acute tolerability of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler, AstraZeneca) administered as a high dose. Fourteen patients with asthma receiving budesonide/formoterol maintenance treatment (two inhalations of 160/4.5 microg twice daily) inhaled 10 additional doses of budesonide/formoterol 1600/45 microg (total daily dose including morning dose of maintenance treatment 1920/54 microg) or formoterol 45 microg (Oxis Turbuhaler, AstraZeneca; total daily dose including morning dose of maintenance treatment 54 microg formoterol) or placebo in addition to the morning dose of maintenance treatment on 3 separate study days. Serum potassium, pulse rate, blood pressure and ECG were assessed at regular intervals over a 12-h period following dosing. Blood glucose and plasma lactate were assessed over 3 h following dosing. Changes in serum potassium, pulse rate, blood pressure, QTc, blood glucose and plasma lactate occurring with budesonide/formoterol, though statistically significantly different from placebo (P<0.05), were considered clinically unimportant. No clinically relevant differences were identified between active treatments. In conclusion, budesonide/formoterol in a single inhaler is well tolerated at high doses such as might be used by patients using budesonide/formoterol for relief of symptoms of asthma.

Topics: Adrenal Cortex Hormones; Adult; Asthma; Blood Glucose; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Drug Tolerance; Ethanolamines; Female; Hemodynamics; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome

Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed.. FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout.. Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly.. Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchoconstrictor Agents; Budesonide; Child; Child, Preschool; Cohort Studies; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Hypersensitivity; Immunoglobulin E; Leukocyte Count; Male; Methacholine Chloride; Nedocromil; Nitric Oxide; Respiration; Respiratory Function Tests; Ribonucleases; Severity of Illness Index; Skin Tests; Spirometry; Statistics, Nonparametric

Because of its non-electrostatic properties the metal Nebuchamber (NC) valved holding chamber (VHC) delivers a greater mass of aerosol to the mouth than the polypropylene Aerochamber (AC) VHC. Delivery of more aerosol to the lungs may also increase systemic absorption of inhaled corticosteroids (ICS) and hypothalamo-pituitary-adrenal (HPA) suppression.. Thirty children (mean 4.3 (SD 0.3) years) received 200 micro g budesonide twice daily by NC or AC, both with the mask provided, in a randomised, two month crossover trial. Twenty four hour urinary free cortisol (UFC) was determined as a measure of HPA suppression.. UFC decreased from 42.3 (7.8) nmol UFC/nmol creatinine control to 26.2 (2.4) (p = 0.06 v control) after AC, and to 24.5 (2.5) (p = 0.04 v control) after NC (p = 0.4 AC v NC).. Despite a greater total dose delivered to the mouth, NC is not associated with greater HPA suppression when using 400 micro g/day budesonide under real life conditions in young children.

Topics: Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Inhalation Spacers; Pituitary-Adrenal System; Polypropylenes; Stainless Steel

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Budesonide; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Middle Aged; Reference Values; Regional Blood Flow; Severity of Illness Index; Vasoconstriction

Inhaled corticosteroids are the agents of choice for treating persistent asthma.. To evaluate the long-term efficacy and safety of budesonide inhalation powder (Pulmicort Turbuhaler) in patients with mild to severe persistent asthma.. Patients (n=1133) received open-label budesonide (dose range, 100-800 microg b.i.d.) for 52 weeks following 2 weeks to 5 months of treatment in one of four double-blind, placebo-controlled studies. Patients, identified before the double-blind studies, included adults (n=249) not receiving corticosteroids, adults (n=384) and children (n=356) previously maintained on inhaled corticosteroids, and adults (n=144) previously maintained on oral corticosteroids.. Mean forced expiratory volume in 1 sec was 68.2% of predicted normal (n=1133) at baseline (mean from two visits before randomization), 74.4% (n=1132) at the end of double-blind treatment, 81.3% (n=971) at week 52, and 80.1% (n=1125) at last observation (including patients who discontinued early). Sixty-four patients maintained on oral corticosteroids before double-blind treatment entered the open-label study off oral corticosteroids, 58 of whom (91%) remained oral corticosteroid-free throughout the study. There was no evidence of basal or cosyntropin-stimulated hypothalamic-pituitary-adrenal axis function suppression, and the most commonly occurring adverse events were respiratory infection, sinusitis, and pharyngitis.. During this 52-week, open-label study, budesonide maintained the improved pulmonary function and decreased oral corticosteroid use observed during previous double-blind treatment and was well tolerated, supporting its long-term use in adults and children with mild to severe persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Powders; Time Factors

A budesonide/formoterol single inhaler has been developed for convenient treatment of patients whose asthma is inadequately controlled by inhaled glucocorticosteroids alone.. To compare long-term safety and efficacy of budesonide/formoterol single inhaler with budesonide plus formoterol via separate inhalers in adults with asthma.. In this open, randomized, parallel-group 6-month extension conducted in a subset of centres from a previous 6-month study, patients (n=321) received two inhalations bid of budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg delivered dose or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler) via separate inhalers.. Significantly fewer patients receiving budesonide/formoterol single inhaler withdrew compared with budesonide plus formoterol (9 vs. 19%, P=0.008). Incidence and severity of AEs were low and similar in both groups. No clinically important differences between groups, or changes, were identified in laboratory measurements, vital signs or ECG. Treatments produced similar improvements in lung function, ACQ scores and Mini AQLQ domains that were maintained throughout 12 months.. Budesonide/formoterol in a single inhaler is as safe and effective in the long-term treatment of asthma as budesonide plus formoterol via separate inhalers. The lower number of withdrawals with budesonide/formoterol may reflect better adherence to treatment compared with budesonide plus formoterol.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome; Vital Capacity

Current asthma management employing inhaled corticosteroids (ICS) and longacting b2-agonists (LABA) aims to rapidly achieve and then maintain overall asthma control including symptoms with minimal medication. This study compared self-guided adjustable maintenance dosing with budesonide/formoterol in a single inhaler with fixed dosing.. In an open-label, parallel-group, multicentre study, 127 asthmatic patients, well controlled on ICS and LABA, were treated with budesonide/formoterol (Symbicort) Turbuhaler) 200/6 mg (equivalent to 160/4.5 mg delivered dose) 2 inhalations bid for 4 weeks, and were then randomised to budesonide/formoterol adjustable dosing (n = 69) (guided self-adjustment of dose: 1 inhalation bid or 2 inhalations at night with interim step ups to 2 inhalations bid and if not sufficient up to 4 inhalations bid for 14 days) or fixed dosing (2 inhalations bid) (n = 58) for 12 weeks.. Patients used adjustable dosing effectively; >50% used a decreased maintenance dose on >50% of the days. Seventy-two percent (50/69) from the adjustable-dosing group reduced their maintenance dose within the first 2 treatment weeks. Thirteen adjustable-dose patients (18.8%) never reduced their dose and 4 (5.8%) stepped up their dose. Symptom severity (NHLBI severity grade) decreased in both groups; however, the decrease was only statistically significant (p = 0.004) in the adjustable-dosing group. Treatment failures occurred in 17% and 24% of patients (adjustable and fixed dosing, respectively p = 0.35). Nocturnal awakenings (0.057 vs. 0.067/night, p = 0.006) and rescue medication use (0.15 vs. 0.23 inhalations/day, p <0.0001) were significantly less frequent with adjustable dosing, and the average daily medication dose was significantly reduced (3.0 vs. 3.9, p <0.0001) compared with fixed dosing. Lung function measurements (FEV1 and PEF) were not significantly different between groups during the study. There were no asthma-related hospital admissions.. Asthma patients on adjustable maintenance dosing with budesonide/ formoterol maintained control of symptoms using significantly less medication overall than fixed dosing. Thus, adjustable maintenance dosing achieved guideline goals of effective asthma control at an appropriately low maintenance dose. However, larger studies on adjustable maintenance dosing are needed.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Switzerland; Treatment Outcome

Pharmacokinetic studies can be used to measure lung dose of inhaled drugs. The aim of this study was to compare the lung deposition of budesonide (BUD) inhaled from Turbuhaler (AstraZeneca, Lund, Sweden) and fluticasone propionate (FP) inhaled from Diskus (GlaxoSmithKline, London, UK) and to assess if the study design used for pharmacokinetic studies can be simplified. Plasma levels of BUD and FP were measured for 21 hours on five separate days in 15 patients aged 8 to 14 years: (1) Intravenous infusion of 200 microg BUD, (2) intravenous infusion of 200 microg fluticasone dipropionate, (3) inhalation of 800 microg BUD via Turbuhaler, (4) inhalation of 750 microg FP via Diskus, and (5) inhalation of BUD and FP on the same day. Charcoal was ingested to eliminate drug uptake from the gastrointestinal tract. The mean lung deposition of drug after Turbuhaler and Diskus inhalation was 30.8 and 8.0% when BUD and fluticasone were administered on separate days and 29.5% (BUD) and 7.6% (fluticasone) when the two drugs were inhaled on the same day. Lung deposition is four times higher in children after inhalation from Turbuhaler than after inhalation from Diskus. Pharmacokinetic studies with BUD and FP can be simplified because the two treatments can be administered on the same day.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Biological Availability; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Female; Fluticasone; Glucocorticoids; Humans; Infusions, Intravenous; Lung; Male; Metered Dose Inhalers; Tissue Distribution

Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD.. HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful.. There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful.. Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Fluticasone; Humans; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome

To compare the effects of 2 nebulizable controller asthma medications on caregiver and pediatric quality of life.. In this 52-week, randomized trial, children aged 2 to 6 years with mild to moderate persistent asthma received budesonide inhalation suspension 0.5 mg (total daily dose) once or twice daily (n = 168) or cromolyn sodium nebulizer solution 20 mg 4 times daily (n = 167) for 8 weeks, with dosage adjustment thereafter at the investigators' discretion. The Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), Compliance/Caregiver Satisfaction Questionnaire (CCSQ), Modified Child Health Questionnaire-Parent Form 50 (CHQ-PF50), and Functional Status-II(R) (FS-II[R]) Questionnaire were administered at baseline and weeks 8, 28, and 52. Global assessments of ease of asthma management and child health status were obtained from caregivers and physicians at the end of the study.. Improvements from baseline in domain-specific (activities and emotional function) and total PACQLQ scores were greater at each time point (weeks 8, 28, and 52) for caregivers of patients treated with budesonide compared with caregivers of patients receiving cromolyn sodium. Only the budesonide group met the criterion for a clinically important improvement (>or=0.5 unit change) in all PACQLQ domains by week 8, which was maintained at weeks 28 and 52. Moreover, improvements surpassed the criterion for moderate clinical importance (1.0 unit change) in all PACQLQ domains for the budesonide group, but this level of improvement was only achieved in the activities domain (at week 28) for the cromolyn sodium group. Based on the CCSQ, budesonide resulted in greater caregiver satisfaction, treatment convenience, ease of use, and compliance compared with cromolyn sodium. Thus, 90.7% of caregivers in the budesonide group were "completely or very satisfied" compared with 53.4% in the cromolyn sodium group. Over half (54.6%) of caregivers in the budesonide group rated budesonide "highly or very convenient" compared with 23% for cromolyn sodium; 77% rated budesonide "extremely or very easy" to use compared with 47% for cromolyn. Adherence with daily medication regimens was reported for 76% of children in the budesonide group compared with 57% in the cromolyn sodium group. Child health status, as indicated by mean FS-II(R) scores, showed improvements from baseline in both groups at weeks 8, 28, and 52. There was a trend for these improvements to be superior in the budesonide group. Additionally, budesonide was superior to cromolyn sodium in caregiver and physician global assessments. At the end of the study, 76% of caregivers of children receiving budesonide reported asthma management to be "a great deal easier" compared with the start of the study, and 74% rated the overall health status of their child as "much better now than 1 year ago." In contrast, only 29% and 37% of caregivers whose children received cromolyn sodium provided these respective ratings.. Budesonide inhalation suspension improved the quality of life for caregivers of children with asthma. Caregivers of children treated with budesonide had significantly fewer limitations in daily activities and emotional functioning compared with caregivers of children treated with cromolyn sodium nebulizer solution. The improvements in caregiver quality of life occurred earlier with budesonide compared with cromolyn sodium. Only caregivers in the budesonide group had a clinically important mean change from baseline in all PACQLQ domains by week 8. These benefits were maintained at week 52. Children treated with budesonide inhalation suspension and cromolyn sodium experienced improvements in health status, assessed using the FS-II(R). The greatest differences between treatments were seen in the disease-specific portion of the FS-II(R), which relates impairments in functional status to the child's illness. Caregiver and physician global assessment indicated significantly better overall child health after 1 year of treatment with budesonide, supporting an improvement in health status. Clinical trials in children 4 to 16 years of age with asthma have demonstrated greater effectiveness of inhaled corticosteroids versus cromolyn sodium on several clinical measures of efficacy. Measures of asthma control in this study, reported in detail elsewhere [Leflein et al. Pediatrics 2002;109:866-872], also have shown greater improvements with budesonide therapy. Treatment with budesonide inhalation suspension resulted in a significantly lower mean rate of asthma exacerbations, significantly longer times to first asthma exacerbation, significantly longer times to first additional use of chronic asthma therapy, and significant improvements in asthma symptom scores and breakthrough medication use compared with cromolyn sodium therapy. Additionally, children receiving budesonide inhalation suspension experienced more symptom-free days and episode-free days compared with children receiving cromolyn sodium. Safety profiles were similar between the 2 treatment groups. Budesonide inhalation suspension was associated with significantly greater caregiver satisfaction, convenience, ease of use, and compliance compared with cromolyn sodium nebulizer solution. This greater caregiver satisfaction and quality of life may be related to the greater asthma control achieved in children treated with budesonide therapy compared with cromolyn sodium. In addition, the convenience of once- or tw

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Caregivers; Child; Child, Preschool; Cromolyn Sodium; Health Status; Humans; Job Satisfaction; Nebulizers and Vaporizers; Patient Compliance; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Suspensions

Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials, high dropout rates have threatened the success of numerous studies.. To evaluate the disease, demographic, and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials.. Predictors of attrition were examined within the Childhood Asthma Management Program (CAMP), a large, multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years.. Eighty-two percent of patients attended all study visits. The tendency to miss visits was increased among older children with milder asthma, lower intellectual and social competence, and more symptoms of behavioral problems and emotional distress. Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts; these patients at baseline had milder asthma; lower cognitive, academic, and social competence skills; and more family conflict and distress than found among participants who remained in the study. The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support.. The 4% dropout rate in CAMP was lower than reported in any previous long-term asthma trial. The findings of milder disease, decreased psychological resources, and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Cognition; Double-Blind Method; Female; Humans; Longitudinal Studies; Male; Nedocromil; Patient Compliance; Patient Dropouts; Patient Education as Topic; Social Behavior; Social Class; Social Support

The objective of the present post-marketing surveillance (PMS) was the evaluation of efficacy, tolerability and acceptance of the novel budesonide (CAS 51333-22-3) multidose dry powder inhaler (MDPI) Novopulmon 200 Novolizer. A total of 3,057 patients suffering from allergic, non-allergic or mixed bronchial asthma were included in the PMS. The study medication was administered by inhalation at a median dosage of 2 x 200 micrograms budesonide/day. In order to evaluate the efficacy of the novel budesonide MDPI, pulmonary functions (peak expiratory flow rate (PEFR) and FEV1) were measured at the start of the treatment and after 4 weeks of treatment. Severity of the following symptoms was evaluated on a four-score scale: cough, wheezing, diurnal dyspnea, nocturnal dyspnea and dyspnea on physical effort. Furthermore, the patients' satisfaction in dealing with the control mechanisms (optical, acoustic, sensory, dose counter, overdose prevention) of this innovative MDPI was assessed. Patients who already had used another inhalation system assessed the control mechanisms of the novel budesonide MDPI in comparison with their previous inhalation system (e.g. fluticasone premetered dose MDPI, non-refillable budesonide MDPI). The patients' compliance and any improvement of compliance by the control mechanisms according to physicians' assessments were evaluated. The novel budesonide MDPI was shown to lead to a decrease in the severity of symptoms. The median total symptom score (0 = no symptoms, 15 = all symptoms severe) decreased from 8 before therapy to 2 after therapy. Pulmonary function measurements supported a relief of the patients' symptoms: The median PEFR increased from 5 l/s before therapy to 6.3 l/s at the end of therapy, with a median individual increase of 1 l/s. The median FEV1 increased from 2250 ml before therapy to 2700 ml at the end of therapy, with a median individual increase of 310 ml. The majority of patients were satisfied with the control mechanisms. 97% of the patients were satisfied with the optical control mechanism, 94% with the acoustic, 78% with the sensory mechanism, 92% with the dose counter and 81% with the overdose prevention. Compliance was assessed by the physicians to be good in 84% of the patients, to be satisfactory in 14% and to be not satisfactory in 2%. An improvement in compliance by the control mechanisms of the inhaler was observed in 80% of the patients. 97% of the patients were satisfied with the control mechanisms, the o

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Female; Forced Expiratory Flow Rates; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Peak Expiratory Flow Rate; Powders; Respiratory Function Tests

Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.. The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.. This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.. Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.. This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Powders; Time Factors

Exacerbations of asthma are often associated with rhinovirus (RV)-induced common colds. During experimental RV-infection in healthy subjects, increased levels of the pro-inflammatory mediator IL-1beta and the anti-inflammatory IL-1 receptor antagonist (IL-1ra) have been found in nasal lavage.. We postulated that the balance between nasal pro- and anti-inflammatory mediator expression is disturbed in asthma, resulting in more extensive inflammation following RV-exposure in asthma.. We determined IL-1ra, IL-1beta, and IL-8 in nasal lavages (days -2, 3, and 6) of non-asthmatics and asthmatics (with and without pre-treatment with the inhaled steroid budesonide) before and after experimental RV16-infection (days 0 and 1).. Following RV16-infection, a significant increase in IL-8 was observed in the placebo- and budesonide-treated asthmatics (P=0.033 and 0.037, respectively), whereas IL-1beta only increased in the two asthma groups combined (P=0.035). A small, but significant, increase in IL-1ra was only observed in the budesonide-treated asthmatics (P=0.047). At baseline, IL-1ra levels were significantly higher in the non-asthmatics than in the placebo-treated asthmatics (P=0.017).. These results demonstrate differences between non-asthmatic and asthmatic subjects in the basal levels of nasal cytokines and their inhibitors, and in the effect of experimental RV-infection on these levels. The results indicate that RV may enhance inflammation more markedly in asthmatics, and suggest that this may in part be explained by lower IL-1ra levels. In addition, the observation that budesonide-treatment may result in higher nasal IL-1ra levels supports the hypothesis that steroids act in part by increasing the endogenous anti-inflammatory screen.

Topics: Asthma; Bronchodilator Agents; Budesonide; Common Cold; Double-Blind Method; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Nasal Lavage Fluid; Rhinovirus; Sialoglycoproteins

Our objective was to assess whether administration of 25-OH-vitamin D to children with asthma treated with inhaled dry-powder budesonide 400 microg daily affects short-term growth or markers of bone turnover. We utilized a randomized, double-blind, two-period crossover trial with run-in and washout periods of 2 weeks and treatment periods of 4 weeks duration. The setting was an Outpatient clinic in a secondary referral center. Subjects included 14 boys and 3 girls with a mean age of 11.7 (range, 6.1-14.4) years. Interventions included 15 microg (600 IU) 25-OH-vitamin D (cholecalciferol) in one tablet ABCDin(R) once daily in the morning. Primary outcome measures were: lower leg growth rate, serum osteocalcin, and serum markers of type I collagen turnover, i.e., the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal propeptide of type I procollagen (PICP) (formation markers), and the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) (degradation markers). Secondary outcome measures were parameters of asthma control and serum 25-OH-vitamin D. Lower leg growth rate was 0.22 mm/week during vitamin D and 0.25 mm/week during placebo treatment (NS). Osteocalcin was 59.9 and 57.8 microg/l during vitamin D and placebo treatment, respectively, PINP 574 and 565 microg/l, PICP 381 and 382 microg/l, and ICTP 11.5 and 11.1 microg/l, respectively (NS). Serum 25-OH-vitamin D was 76.3 nmol/l and 48.2 nmol/l, respectively (P < 0.001). There were no statistically significant differences in measures of pulmonary function. In conclusion, administration of 25-OH-vitamin D does not affect short-term growth or markers of bone turnover in children with asthma treated with inhaled dry-powder budesonide 400 microg daily.

Topics: Administration, Inhalation; Adolescent; Asthma; Biomarkers; Bone Development; Bronchodilator Agents; Budesonide; Child; Collagen Type I; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Growth; Humans; Leg; Male; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Vitamin D

We conducted this study to compare the efficacy and safety of once-daily mometasone furoate (MF) administered by dry powder inhaler (DPI) with once-daily budesonide (BUD)-DPI and placebo in patients with moderate persistent asthma previously using twice-daily inhaled corticosteroids. A total of 262 patients (> or = 12 years of age) with moderate persistent asthma were randomised to once-daily morning treatment with MF-DPI 440 microg (metered dose), BUD-DPI 400 microg (metered dose), or placebo in an eight-week, multicentre, placebo-controlled, double-blind, double-dummy study. The primary efficacy variable was percent change in FEV1 from baseline to endpoint (last evaluable visit). At endpoint, the percent change in FEV1 was significantly greater (p < 0.01) following treatment with MF-DPI 440 microg (8.9%) than with both BUD-DPI 400 microg (2.1%) and placebo (-3.9%). Secondary efficacy variables, including morning and evening peak expiratory flow rates, albuterol use, percentage of asthma symptom-free days, and physician-evaluated response to therapy were also significantly improved at endpoint in the MF-DPI group compared with both the placebo and BUD-DPI groups (p < 0.05). Both active treatments were well tolerated. In conclusion, once-daily treatment in the morning with MF-DPI 440 microg significantly improved pulmonary function and asthma control compared with morning administration of BUD-DPI 400 microg and placebo.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Forced Expiratory Volume; Humans; Middle Aged; Mometasone Furoate; Pregnadienediols; Respiratory Function Tests; Treatment Outcome

Inhaled, long-acting beta2-agonists or antileukotrienes are alternatives as add-on therapy for asthmatic children taking regular inhaled steroids. Any complementary effects would be relevant to the choice between these alternatives. Exhaled nitric oxide (FeNO) may reflect these effects.. To compare the control of FeNO provided by salmeterol or montelukast add-on therapy in asthmatic children undergoing regular maintenance treatment with a daily dose of 400 microg of budesonide.. The study included children with increased FeNO despite regular treatment with budesonide, 400 microg/d, and normal lung function. Montelukast, 5 mg/d, salmeterol, 50 microg twice daily, or placebo was compared as add-on therapy to budesonide, 400 microg, in a randomized, double-blind, double-dummy, crossover study.. Twenty-two children completed the trial. The geometric mean FeNO level was 20 ppb (95% confidence interval [CI], 15-27 ppb) after salmeterol, which was significantly higher than after montelukast (mean, 15 ppb; 95% CI, 11-18 ppb; P = 0.002) and placebo (mean, 15 ppb; 95% CI, 10-21 ppb; P = 0.03). There was no difference in FeNO between the montelukast and placebo groups. Mean forced expiratory volume in 1 second (FEV1) was significantly increased after salmeterol (mean, 2.63 L; 95% CI, 2.34-2.91 L) compared with placebo (mean, 2.48 L; 95% CI, 2.19-2.77 L). Montelukast (mean, 2.57 L; 95% CI, 2.33-2.80 L) was no different than placebo.. The FeNO levels were significantly higher after salmeterol add-on treatment compared with both placebo and montelukast add-on treatment. Salmeterol significantly improved lung function (FEV1) compared with placebo and nonsignificantly compared with montelukast. Montelukast failed to reduce FeNO and improve lung function compared with placebo in this group of children taking regular budesonide, 400 microg.

Topics: Acetates; Administration, Inhalation; Adolescent; Albuterol; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Humans; Nitric Oxide; Quinolines; Salmeterol Xinafoate; Sulfides

The objective of this study was to analyze data on parents' adherence to their child's prescribed nebulizer treatment regimen and compliance with the demands of the nebulizer and the face mask. Data on adherence and compliance were recorded in a 24-week double-blind, randomized, parallel-group study with budesonide inhalation suspension in 125 young children with mild to moderate asthma. Budesonide was administered with an Adaptive Aerosol Delivery (AAD) system, which recorded adherence to treatment and compliance with the AAD system. A total of 35,481 treatments were recorded and analyzed. A study questionnaire regarding the parents' and children's acceptance of the AAD system has also been analyzed. The adherence to the treatment regimen was 91.3%, and the compliance with the AAD system was 90.4%. True adherence, the product of adherence and compliance, was 82.5%. Approximately 90% of the parents found the face mask easy to seal and the AAD equipment easy to use, and over 90% of the children accepted it within 1 week. In conclusion, the results indicate that the AAD system could be of real clinical advantage for treatment of asthma in young children.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Equipment Design; Female; Humans; Infant; Male; Masks; Nebulizers and Vaporizers; Parents; Surveys and Questionnaires

There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes. We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration.. A randomized double-blind, placebo-controlled design was used. Twenty-nine children ages 6 months to 3 years were divided into three groups: (1) high starting dose: 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment.. Before treatment and after 8-10 days of treatment, there was no significant difference in mean serum cortisol concentration in the high starting dose, low-dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation.. The administration of nebulized suspension of budesonide at a high starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8 days was safe, causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Infant; Male; Nebulizers and Vaporizers; Recurrence; Respiratory Sounds; Safety; Time Factors

Asthma is a disease that demonstrates chronic Th2 lymphocyte-mediated pulmonary inflammation. We hypothesized that cytokines produced by asthmatic lung inflammation bias the immune response to antigens administered systemically toward a Th2 response, as assessed by serum IgE antibody and lymphocyte-secreted IL-4 and IL-5. We also hypothesized that treatment of asthmatic children with local anti-inflammatory agents reduces this cytokine-mediated Th2 influence. We systemically immunized groups of asthmatic children (n=29) who were participating in a long-term, randomized, placebo-controlled clinical trial of inhaled anti-inflammatory therapy (Childhood Asthma Management Program) and nonasthmatic children (n=12) with hepatitis B (Hep B) antigen, and examined their antigen-specific antibody and lymphocyte cytokine secretion profiles. The asthmatic population demonstrated an increased amount of Th2-mediated serum IgE anti-Hep B antibody, as compared to nonasthmatic children; but comparable amounts of IgG1, IgG2, IgG3, IgA, and IgM anti-Hep B antibody and lymphocyte IFNgamma, IL4, and IL5. There was no significant difference of antibody isotype or cytokine production between asthmatic subjects receiving treatment with budesonide or nedocromil, as compared to placebo. In conclusion, there is a subtle bias in responses to systemic immunization in children with asthma, but anti-inflammatory therapy does not affect this bias. The findings support the concept that the Th2 bias may be largely genetic. Importantly, we confirmed that children with asthma, including even those on inhaled corticosteroids, responded to Hep B immunization as well as did nonasthmatic children with the major isotypes of anti-Hep B antibody, suggesting that vaccine protection against hepatitis B is not influenced by inhaled steroid therapy.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cytokines; Drug Interactions; Female; Hepatitis B Antibodies; Hepatitis B Vaccines; Humans; Male; Nedocromil

A guided, adjustable-dosing regimen with budesonide/formoterol was investigated in asthma patients. In a randomised, open, multicentre study, 1034 patients received budesonide/ formoterol (Symbicort, Turbuhaler,) 80/4.5 microg or 160/4.5 microg (depending on pre-study inhaled corticosteroid dose) two inhalations twice daily for four weeks, followed by adjustable or fixed maintenance dosing for six months. Patients receiving adjustable dosing stepped down to one inhalation twice daily if symptoms were controlled and could, if symptoms worsened, step up to four inhalations twice daily for one or two weeks according to a self-guided management plan. The primary efficacy variable was occurrence of exacerbations. Compared with fixed dosing, adjustable dosing was associated with fewer patients experiencing exacerbations (6.2% vs 9.5%, NNT 30, p<0.05), fewer daily inhalations of budesonide/formoterol (2.35 vs 3.95, p<0.001), lower costs (six-month saving Euros 98, p<0.001) and was similarly well tolerated. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control than fixed dosing, and reduces costs.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Treatment Outcome

This open, multinational, randomised, parallel-group, six-month extension conducted in the Swedish centres of a previous six-month study compared the costs of a total of 12 months of treatment with budesonide/formoterol in a single inhaler with budesonide plus formoterol separate inhalers in 320 adults with asthma. Patients received budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 mg delivered doses, two inhalations b.i.d., or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler). Direct costs and indirect costs were estimated. Budesonide/formoterol treatment was associated with reduced healthcare service utilisation and statistically significant reductions in direct (SEK1595, p=0.0004) and total costs (SEK1884, p=0.043) per person per year compared with budesonide plus formoterol. Budesonide/formoterol reduced the average annual emergency room admission cost per person by SEK489.7 (31% of direct cost reduction) and physician costs by SEK235.4 (15%).The direct cost of study, relief and other medication was reduced by SEK893.8 (47% of total reduction). There were no statistically significant differences in efficacy and safety parameters following treatment with budesonide/formoterol from single or separate inhalers, other than a significantly lower proportion of withdrawals with the single inhaler (9.2% vs 19.4%, p=0.008). In summary, budesonide/formoterol treatment from a single inhaler reduced 12-month treatment costs compared with separate inhalers, while maintaining at least as good control of asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Health Care Costs; Humans; Male; Middle Aged; Prospective Studies; Sweden; Treatment Outcome

Regular anti-inflammatory treatment is essential in treating persistent asthma. Most commonly, inhaled corticosteroids (ICS) are used. However, especially in children, there is concern about the long-term safety of ICS such that doses should be kept to a minimum. The use of theophylline has decreased because of frequent side-effects in therapeutic doses. In adults, there have been reports about an immunomodulatory effect of low-dose theophylline. To study the clinical and immunomodulatory effect in children, 36 patients (mean age 12.5 SD 2.4 years) with moderate, persistent asthma on regular ICS were recruited into a placebo-controlled, double-blind study. After a 6-week run-in period, patients received either theophylline 10 mg/kg bodyweight or placebo for 12 weeks. Diary cards, lung function, peripheral blood lymphocyte subpopulations and serum eosinophil cationic protein (sECP) were assessed. In the treatment group, mean serum theophylline was 7.1 mg/l. There was no change in symptoms or use of rescue medication. Mean (SD) peak expiratory flow (PEF) increased from 86% (24) to 95% (18) predicted. sECP decreased from 43.2 microg/l (32.5) to 26.5 microg/l (16.9) (p = 0.02). Lymphocyte subpopulations did not change. The study failed to show a beneficial clinical or an immunomodulatory effect of theophylline when used in low doses. These results do not support a more important role of theophylline in the long-term treatment of moderate childhood asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Airway Resistance; Androstadienes; Antigens, Differentiation, T-Lymphocyte; Asthma; Biomarkers; Blood Proteins; Bronchodilator Agents; Budesonide; Child; Child Welfare; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Granule Proteins; Female; Fluticasone; Forced Expiratory Volume; Germany; Humans; Lymphocyte Count; Lymphocyte Subsets; Male; Peak Expiratory Flow Rate; Predictive Value of Tests; Respiratory Function Tests; Ribonucleases; School Health Services; T-Lymphocytes; Theophylline; Time; Treatment Outcome; Vital Capacity

Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma.. Twenty-nine patients with mean FEV1 (+/- SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 microg + formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD 400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg + salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP 250 microg alone twice daily. Measurements were made at baseline and following each randomized treatment.. FEV1 increase from pretreatment baseline as mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/- 1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/- 1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments.. Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchi; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

Nitric oxide in exhaled air is regarded as an inflammation marker, and may be used to monitor the anti-inflammatory control from inhaled corticosteroids (ICSs). However, this response to ICSs exhibits a heterogeneous pattern.. The study aimed to describe the independent variables associated with the heterogeneity in the response of exhaled nitric oxide to ICSs.. Exhaled nitric oxide (FeNO), lung function, bronchial hyper-responsiveness (BHR), specific IgE to common inhalant allergens, blood eosinophils, other atopic manifestations and variants in nitric oxide synthethase 1 (NOS1) gene were studied in a double-blind, placebo-controlled crossover comparison of budesonide (BUD) Turbohaler 1600 mcg daily vs. placebo in asthmatic schoolchildren.. Forty children were included in the study from a screening of 184 asthmatic children with moderately persistent asthma, well controlled on regular BUD 400 mcg daily: 20 children with normal FeNO and 20 with raised FeNO. FeNO, BHR and forced expiratory volume in 1 s improved significantly after BUD 1600 mcg (BUD1600). However, FeNO after ICS treatment exhibited a Gaussian distribution and FeNO was significantly raised in 15 children. Allergy and BHR, but none of the other independent variables under study were significantly related to FeNO after BUD1600.. Exhaled nitric oxide exhibited a heterogeneous response to ICS in asthmatic schoolchildren. Allergy and BHR were driving FeNO level independently of high-dose steroid treatment. This should be considered when using FeNO for steroid dose titration and monitoring of ICS anti-inflammatory control in asthmatic children.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Case-Control Studies; Child; Cross-Over Studies; Double-Blind Method; Female; Humans; Lung; Male; Nebulizers and Vaporizers; Nitric Oxide; Regression Analysis

The Inhaled Steroid as Regular Therapy in Early Asthma (START) study reported that early intervention with budesonide in mild persistent asthma reduces severe asthmatic events and improves symptom outcomes and lung function in adults and children.. We sought to estimate the incremental cost-effectiveness of early intervention with budesonide, as observed within the START study.. START was a randomized, 3-year controlled trial of budesonide in early onset mild asthma among 7165 subjects ages 5 to 66 years. Three age groups (5-10, 11-17, and >or=18 years) were studied separately and overall. Differences in the probability of emergency treatments, symptom-free days (SFDs), and costs of health care were determined. Incremental cost-effectiveness ratios were estimated from the health care payer and societal perspectives.. Compared with usual therapy, patients receiving budesonide experienced an average of 14.1 (SE, 1.3) more SFDs per year (P <.001), fewer hospital days (69%, P <.001), and fewer emergency department visits (67%, P <.05). From the health care payer perspective, the net cost of early use of budesonide was an additional US dollars 0.42 (SE, dollars 0.04) per day, and the resultant cost-effectiveness ratio was US dollars 11.30 (95% CI, US dollars 8.60-US dollars 14.90) per SFD gained. From the societal perspective, the cost offsets of lower absence from school or work reduced the net cost of early budesonide to US dollars 0.14 (SE, US dollars 0.07) per day and decreased the cost-effectiveness ratio to US dollars 3.70 (95% CI, US dollars 0.10-US dollars 8.00). Early intervention was more effective and cost saving in the youngest age group.. Long-term treatment with budesonide appears to be cost-effective in patients with mild persistent asthma of recent onset.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cost-Benefit Analysis; Double-Blind Method; Humans; Middle Aged; Research Design; Treatment Outcome

The purpose of this study was to compare the efficacy and safety of the inhaled budesonide, sustained-release theophylline and montelukast, a leukotriene receptor antagonist, in patients with mild persistent asthma. In this single-center, randomized, parallel-group study that not designed blindly and placebo-controlled manner, 74 patients with mild persistent asthma were treated with either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once daily, or sustained-release theophylline 400 mg once daily for 3 months. In all three treatment groups, improvements were attained in overall asthma control. Asthma symptom scores and supplemental beta2-agonist use were quite the same in all three treatment groups (P>0.05). Although inhaled budesonide group resulted in significantly greater improvements compared with the other two groups in the lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline variability and there was no statistically significant difference among the groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were experienced by 16% of the patients in the montekulast group, by 12.5% of the patients in the theophylline group, and by none of the patients in the budesonide group. The adverse event in each of the three groups was 12%, 16% and 16.7%, respectively. It is concluded that the most important clinical parameters do not point that one of the treatments is more effective than others. Treatment with inhaled corticosteroid is preferred, but sustained-release theophylline and leukotriene antagonists are alternative controller medications in mild persistent asthma.

Topics: Acetates; Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Cyclopropanes; Delayed-Action Preparations; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Sulfides; Theophylline; Treatment Outcome

The efficacy and safety of Symbicort (budesonide and formoterol in a single inhaler) were compared with those of a high dose of the commonly used corticosteroid fluticasone propionate in patients with moderate persistent asthma.. This randomized, double-blind, double-dummy, parallel-group study involved 373 patients with asthma (mean age 42 years; FEV(1) 78% of predicted; reversibility 21%). After a 2-week run-in period, during which patients received budesonide 200 microg twice daily, they were randomly assigned to treatment with either Symbicort Turbuhaler (budesonide/formoterol 160/4.5 microg, one inhalation twice daily) or Flovent/Flixotide Diskus (fluticasone propionate 250 microg twice daily) for 12 weeks.. Significantly greater increases in morning PEF, the primary efficacy variable, were observed in patients treated with budesonide/formoterol compared with fluticasone propionate (27.4 L/min vs 7.7 L/min; p < 0.001). Evening PEF and clinic FEV(1) also favored budesonide/formoterol compared with fluticasone propionate (p < 0.001), as did use of reliever medication (p = 0.04) and the proportion of reliever-free days (p < 0.001). There were also numerical improvements in symptom-free days (60.4% vs 55.5%), night-time awakenings (7.9% vs 9.6%) and asthma-control days (57.8% vs 52.4%) in favor of budesonide/formoterol. The risk of an exacerbation was reduced by 32% in the budesonide/formoterol group compared with the fluticasone propionate group (p < 0.05). Both treatments were well tolerated.. Symbicort (budesonide/formoterol in a single inhaler) was more effective than a high dose of fluticasone propionate in improving lung function, reducing use of reliever medication and improving control of moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome

This study was undertaken to investigate whether budesonide 4001 microg twice daily (Chiesi Farmaceutici S.p.A.) given with the HFA-134a propellant is equivalent in efficacy and safety to the same dose regimen delivered with the marketed CFC product in adult asthmatics with mild to moderate persistent asthma; the effects of budesonide HFA 800 microg once daily were also studied. After a 2-week run-in, a total number of 98, 103 and 97 patients were assigned to the 12-week treatment with budesonide given with HFA or CFC twice daily (morning and evening), or HFA once daily (morning), respectively. The main outcome variable morning PEFR, as well as evening PEFR and clinical symptoms (day-time and night-time asthma attacks, number of asthma-induced night-time awakenings and overall symptoms' scores) were measured daily by patients. Other standard pulmonary function testing were measured at clinic visits. A blood sample for morning serum dosing (8.00-10.00 AM) was taken at baseline and at endpoint. Adverse events and vital signs were also recorded. Significant improvements at endpoint in morning and evening PEFR, as well as in clinic PEFR and MEF50, were observed in both the twice daily groups only. An exact proof of equivalence between HFA and CFC given twice daily was demonstrated for the primary parameters, morning PEFR (equivalence pre-defined limits were +/- 40.27 l/min, difference between means = 4.0 l/min and 95% CI -6.9-14.9) and secondary parameters as evening PEFR: (limits +/- 40.19 l/min, difference between means = 2.1 l/min and 95% Confidence interval (CI) -9.4-13.5) and FEV1 (limits +/- 0.27 l, difference between means = 0.0 l and 95% CI -0.11-0.10). Less evident (but within limits) proofs of equivalence were shown in the comparisons with the once daily group. No substantial differences between the three groups were observed for the other efficacy variables, including symptoms and use of rescue salbutamol, which significantly improved over the run-in values in all groups. Minimal and non-significant decreases over pre-treatment values were observed in the three groups for morning serum cortisol levels: the analysis of individual data has shown a better outcome in the HFA twice daily regimen, compared with the other two groups. Again, a similar amount of patients in both the twice daily groups reported drug-related adverse events, which were more frequent in the once daily HFA group. Therefore, the results of this study have shown that inhaled budes

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Administration Schedule; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Ventilation; Therapeutic Equivalency; Treatment Outcome

The aim of the present study was to demonstrate an equivalent asthma control and safety of inhaled budesonide 200 microg unit-dose via a spacer device (Jet Spacer, Chiesi Farmaceutici S.p.A.) given with an HFA-134a or CFC propellant in stable patients treated with inhaled corticosteroids. A total number of 270 patients, 134 in the HFA-134a group and 136 in the CFC group, completed a 2-week run-in period and were then randomised to receive a daily dose of inhaled budesonide (low dose: 400 microg, medium dose: 800 microg, high dose: 1200 or 1600 microg), defined on the basis of the dose of previous inhaled steroids given twice daily for 12 weeks. Morning and evening PEFR, intake of rescue salbutamol, number of day-time and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR and MEF50) and vital signs were measured at the clinics at study entry, at the start of treatment and after 2, 4, 8 and 12 weeks thereafter. Morning serum cortisol (8.00-10.00 AM) was measured at baseline and in the final visit. Adverse events and vital signs were recorded throughout the total study period. Small increases vs. baseline for lung function (more markedly in the high-dose subsets) and significant decreases of symptoms and use of rescue salbutamol were similarly observed in both groups. Equivalence was demonstrated for the primary endpoint morning PEFR (difference between means = -1.51 l/min; 95% CI: -9.40-6.37 l/min; pre-defined limits: +/- 42.16 l/min, i.e. +/- 10% of the reference LSM) as well as for evening PEFR and FEV1, both in the ITT population or on a per-protocol basis. No statistically significant differences between groups were observed in any of the other efficacy variables. A similar proportion of drug-related adverse events was observed in the two groups, without drug-related serious events in either group. No evidence of adrenal depletion was also noted with both propellants. In conclusion, the budesonide HFA-134a formulation given with a spacer device provided an equivalent asthma control with that of a corresponding CFC product, when administered in stable patients treated with inhaled corticosteroids in a broad range of daily doses. The use of the new propellant did not modify the safety profile of inhaled budesonide.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Chlorofluorocarbons; Dose-Response Relationship, Drug; Female; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Pulmonary Ventilation; Treatment Outcome

Exhaled nitric oxide (eNO) is elevated in several inflammatory airway diseases and is significantly reduced by anti-inflammatory treatment with inhaled steroids. The aim of this randomized, open clinical trial was to evaluate eNO in relation to conventional lung function parameters at rest and after exercise during sequential changes of inhaled steroids in children with persistent asthma. The study consisted of a 4 week run-in period, a 4 week washout phase and a randomized treatment period during which only one group was treated again with inhaled budesonide. After run-in, eNO was reduced to normal values, and rose again during washout. In the patients randomized to steroid treatment, eNO was again decreased, whereas it remained unchanged in the untreated patients. Forced expiratory volume in one second and forced vital capacity at rest and after exercise improved significantly after run-in, but showed no difference after randomization. However there was a strong correlation of eNO with patient compliance. Exhaled nitric oxide was able to differentiate between children briefly treated with or without steroids, the conventional lung-function variables however could not. In practice exhaled nitric oxide may thus be a valuable parameter to monitor adherence to steroids, but less suitable to describe physiologically relevant impairments of lung function.

Topics: Adolescent; Anti-Inflammatory Agents; Asthma; Biomarkers; Budesonide; Child; Exercise; Female; Forced Expiratory Volume; Humans; Lung Compliance; Male; Nitric Oxide; Rest; Vital Capacity

The objective of this study was to compare the efficacy and safety of the second controller medications (long-acting beta2-agonist, leukotriene receptor antagonist and sustained-release theophylline) used in addition to inhaler corticosteroid treatment in moderate persistent asthma. A total of 64 patients with asthma, in the moderate persistent asthma category, were divided into three groups. Patients, all of whom were concurrently using inhaled corticosteroid (Budesonide 400 microg twice daily), were treated for 3 months with either inhaled formoterol 9 microg twice daily (first group), oral zafirlukast 20 mg twice daily (second group), or sustained-release theophylline 400 mg once daily (third group). All of the patients were subjected to assessments on the subject of peak expiratory flow (PEF) variability, forced expiratory volume in 1 sec (FEV1), asthma symptom scores (daytime and night-time), supplemental terbutalin use, asthma exacerbations and adverse events. Over the 3-month treatment period. In all of the three groups, significant improvements were recorded in the lung function, asthma symptom scores and supplemental terbutalin use criteria, as a result oftreatments applied. Formoterol treatment resulted in significantly greater and earlier improvements compared with the other two groups in several criteria: PEF variability (17.9 +/- 2.5; 21.9 +/- 3.2; 23.7 +/- 3.3; P < 0.001); asthma symptom score (daytime) (1.6 +/- 0.5; 1 +/- 0.5; 2.0 +/- 0,5; P < 0.05); asthma symptom score (night-time) (1.2 +/- 0.4; 2.2 +/- 0.5; 16 +/- 0.6; P < 0001); and supplement alter butalin use (1.2 +/- 0.3; 1.8 +/- 0.5; 1.7 +/- 0.5; P < 0.05). However, at the end of the treatment, in all of the three groups studied, improvements were attained in overall asthma control and there was no statistical difference among the groups. Although there were no side effects which required the discontinuation of the treatment, it was observed that the maximum side effect was in the second group (20%, 31.6% and 20%, respectively). In conclusion, in patients who still have symptoms on treatment with inhaled corticosteroids, the addition of a long-acting beta2-agonist, leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach, and, in addition to inhaled corticosteroids, any one of these second controller medications may be chosen in patients with moderate asthma.

Topics: Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Phosphodiesterase Inhibitors; Respiratory Mechanics; Sulfonamides; Theophylline; Tosyl Compounds

The deposition of budesonide at fast (60 l min(-1)) and slow (301 min(-1)) inspiratory flow rates from Airmax, a new multi-dose dry powder inhaler, was compared with that from Turbuhaler and a standard pressurized metered dose inhaler (pMDI). Twelve patients with mild to moderate asthma took part in a five-way randomized crossover study, and inhaled a single nominal dose of 200 microg budesonide, labelled with 99mTc, on each study day. Deposition was determined by gamma scintigraphy. At the fast flow rate, Airmax and Turbuhaler deposited 25.8+/-6.5% (mean +/- sD) and 29.8+/-6.9%, respectively of the delivered dose in the whole lung (P = 0.080). At the slow flow rate, Airmax deposited 28.3+/-5.6%, Turbuhaler 22.7+/-5.6% and pMDI 12.1+/-3.4%. Using data on emitted doses determined in vitro, it was estimated that Airmax deposited 53.1+/-13.3 microg and 43.6+/-8-6 microg budesonide in the lungs at 60 l min(-1) and 30 l min(-1) respectively whilst Turbuhaler deposited 48.3+/-11.2 microg at 60 l min -and 24.2+/-6.0 microg at 30 l min(-1). In conclusion, lung deposition of budesonide from Airmax was comparable to that of Turbuhaler at a high flow rate but was markedly superior to Turbuhaler and pMDI at a lower flow rate. Unlike Turbuhaler, Airmax performs with relative flow-rate independence.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Female; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Radionuclide Imaging; Technetium

Asthma is characterized by inflammation of the airways and long-term treatment with inhaled glucocorticosteroids improve clinical control in patients previously treated with inhaled rescue beta-2 agonist. We investigated whether the dose of inhaled glucocorticosteroid was related to outcome compared with oral theophylline. Budesonide 800 microg bd, budesonide 200 microg bd, or theophylline (Theo-Dur 300 mg bd was given double-blind, double-dummy and randomized, in a parallel group design for 9 months; when therapy was stopped patients were followed for an additional 3 months. Forced expiratory volume in 1 sec (FEV1), bronchial reactivity and asthma symptom scores were assessed before entering the study and after 1, 2, 3, 5, 7, and 9 months of treatment and monthly after treatment was stopped. Eighty-five patients (38 females and 47 males) were enrolled in the study during 1 1/2 year. Withdrawal from the study due to exacerbations during the treatment period was significantly increased (P <0.01) in the theophylline group. After treatment was stopped more patients withdrew in the budesonide group. In the budesonide 800 microg bd group, FEV1 improved significantly after 1 months treatment (P <0.01) and persisted throughout the study period. In the budesonide 200 microg bd group, FEV1 improved slightly and reached significance (P=0.05) after 5 months of treatment. In the theophylline group, FEV1 was unchanged during the 9 months of treatment. In both budesonide groups, FEV1 deteriorated significantly (P<0.01 and P<0.02, respectively) after termination of study medication and reached pretreatment values during the first month. In the budesonide 800 microg bd group, the concentration of histamine causing a 20% fall in FEV1 (PC20) increased significantly (P<0.01) after 1 months treatment and increased further after 9 months (P<0.0001), equivalent to two doubling dilutions. In the budesonide 200 microg bd, group PC20 histamine significantly increased (P <0.005) after 2 months of treatment and remained constant; theophylline was unchanged. After treatment with budesonide 800 microg bd and 200 microg bd were stopped, PC20 decreased significantly (P<0.002 and P=0.05, respectively) within the first month. PC20 remained unchanged after theophylline was stopped. After budesonide 800 microg bd and 200 microg bd treatment, symptom severity decreased in a dose-related and highly significant manner (P < 0.00001 and P < 0.0001, respectively). With theophylline, asthma sympt

Topics: Administration, Inhalation; Administration, Oral; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Long-Term Care; Lung; Male; Middle Aged; Theophylline; Treatment Outcome

Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with house dust mite allergy and mild asthma (dual responders) participated in a parallel, double-blind study. All patients inhaled a low-dose of allergen on 10 subsequent working days (Days 1-5, 8-12). They were treated with 400 micro g budesonide once daily (n = 13) or placebo (n = 13) from Days -3 to 19. At baseline (Day -6) and on Days 5, 12, and 19 we measured the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)), and percent eosinophils, interleukin (IL)-5/interferon-gamma messenger RNA ratio (in sputum cells by real-time reverse transcription-polymerase chain reaction [RT-PCR]), and eosinophilic cationic protein (ECP) in induced sputum. Symptoms, peak expiratory flow (PEF), FEV(1), and exhaled nitric oxide (NO) were recorded repeatedly during the study. In the placebo group, repeated low-dose allergen exposure resulted in a significant increase in sputum eosinophils (p = 0.043), ECP (p = 0.011), IL-5/IFN-gamma messenger RNA ratio (p = 0.04), and in exhaled NO (p = 0.001), without worsening of symptoms, PEF, or baseline FEV(1) (p > 0.07). In the budesonide group, the changes in PC(20), sputum ECP, and exhaled NO were significantly different as compared with the placebo group (p < 0.03). We conclude that repeated low-dose allergen exposure in asthma can lead to airway inflammation without worsening of symptoms, which can be prevented by inhaled steroid treatment. This suggests that antiinflammatory therapy is beneficial during allergen exposure, even during asymptomatic episodes.

Topics: Administration, Inhalation; Adolescent; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Inflammation; Male; Respiratory Function Tests; Respiratory Tract Diseases; Severity of Illness Index

This study investigated the effect of low dose of budesonide 100 micrograms b.d from a new multi-dose dry powder inhaler (Airmax) and from a conventional inhaler (Turbuhaler) on bronchial hyper-responsiveness, lung function and asthma symptoms in mild stable asthmatics. Twenty-five patients were enrolled into a double-blind double-dummy crossover study with two 4-week treatment periods separated by a 4-week washout. Patients had a mean forced expiratory volume in 1 s (FEV1) of 91 +/- 13% predicted, had previously received inhaled short-acting beta 2-agonists only and had a PC20 to adenosine 5' monophosphate (AMP) < 40 mg/ml. PC20 AMP was assessed at baseline, and at the start and end of each treatment period. Patients recorded peak expiratory flow and symptoms throughout the study. There was a mean increase in PC20AMP from start to end of 3.49 doubling dilutions (DD) in the Airmax group and 2.90 DD in the Turbuhaler group. The difference was 0.60 DD (95% CI--0.47, 1.69) favouring Airmax and the upper limit exceeded the equivalence limit of +/- 1 DD. There were similar improvements in FEV1, daily PEF and symptoms in both groups. The majority of patients preferred treatment with Airmax to Turbuhaler (64 vs. 23%). Both treatments were equally well tolerated. In conclusion, 100 micrograms budesonide bid during 4 weeks from Airmax effectively attenuates the response to AMP in mild asthmatics. Overall Airmax offers equal clinical benefit to Turbuhaler.

Topics: Adult; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Nebulizers and Vaporizers; Patient Satisfaction

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler and Turbuhaler for the delivery of budesonide 200 micrograms/dose twice daily in steroid-naïve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-naïve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 micrograms/day either via Easyhaler (n = 159) or via Turbuhaler (n = 167), plus salbutamol inhalation powder (100 micrograms/dose) via Easyhaler as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler group and 149 in the Turbuhaler group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7-8. At weeks 7-8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from -8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler more acceptable than Turbuhaler. The results show that budesonide via Easyhaler is clinically as effective as Pulmicort Turbuhaler when equal daily doses of budesonide are delivered to steroid-naïve asthmatic patients. Moreover, patients found Easyhaler more acceptable than Turbuhaler, and a majority would prefer Easyhaler if given a choice.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Patient Satisfaction; Peak Expiratory Flow Rate; Treatment Outcome; Vital Capacity

Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.. After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.. Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).. Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Quality of Life; Survival Analysis; Treatment Outcome

In the drive to replace chlorofluorinated hydrocarbons (CFCs) by alternative more environmentally friendly propellants in pressurized metered dose inhalers (pMDIs), Chiesi has developed new inhalers using Modulite technology. The aim was to obtain CFC-free pMDIs which are equivalent, in terms of safety and efficacy, to the previous CFC devices at the same dose. When beclometasone dipropionate (BDP) and budesonide Modulite formulations were compared to the equivalent CFC products there was no significant difference in morning serum cortisol or urinary cortisol excretion, at the maximum recommended daily dose (2000 micrograms or 1600 micrograms respectively). Single dose pharmacokinetic studies in both healthy volunteers and asthmatic patients compared systemic exposure (B17MP levels) for BDP-CFC with BDP Modulite and extrafine BDP-HFA (QVAR). B17MP levels for BDP-CFC and BDP Modulite were comparable, but substantially less than that seen with extrafine BDP-HFA. After 6 weeks of treatment in asthmatic patients, B17MP AUC after inhalation of BDP (1000 micrograms twice-daily) from BDP Modulite was comparable with that obtained after BDP-CFC (Becloforte). Plasma profile of BDP and B17MP were similar after inhalation from BDP Modulite with standard actuator or delivered via a spacer, suggesting that pulmonary delivery of BDP to the lung is similar with both actuators.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Cross-Over Studies; Double-Blind Method; Drug Delivery Systems; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Nebulizers and Vaporizers; Therapeutic Equivalency

In Russia, current therapy for the long-term management of asthma is mainly nonsteroidal. This situation provides the opportunity to evaluate new asthma treatments in a patient cohort with little previous exposure to inhaled corticosteroids.. To compare the effect of formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone, on the health-related quality of life (HRQL) of patients with mild to moderate asthma.. A double-blind, parallel-group, randomized, 12-week study compared formoterol Turbuhaler plus budesonide Turbuhaler and budesonide Turbuhaler alone with an open control group of the investigator's choice of noncorticosteroid therapy. Patients completed the Short Form 36 (SF-36) and the Asthma Quality of Life Questionnaire (AQLQ).. The improvement in HRQL scores for patients treated with noncorticosteroids was significantly less (p < 0.05) than those treated with formoterol plus budesonide and budesonide alone in all domains of the SF-36 and AQLQ with one marginal exception (budesonide versus investigator's choice, SF-36, Mental Component Scale, p = 0.053). Improvements in HRQL scores of formoterol plus budesonide, compared with budesonide alone, although generally higher, were not significantly different. Formoterol plus budesonide was more effective in improving lung function and reducing both symptoms and the need for relief terbutaline inhalation.. Formoterol Turbuhaler plus budesonide Turbuhaler and budesonide Turbuhaler alone significantly improved the HRQL of patients with mild to moderate asthma compared with noncorticosteroid treatment.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Health Surveys; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Quality of Life; Russia; Surveys and Questionnaires; Treatment Outcome

Dry powder inhalers (DPIs) are used to deliver asthma drugs to patients, but lung deposition may depend upon the degree of inspiratory effort. The pulmonary deposition of the glucocorticosteroid budesonide (SMB-Galephar) has been assessed in 12 asthmatic patients when delivered by the Monodose inhaler (Miat, Milan, Italy); the Pulmicort Turbuhaler DPI (AstraZeneca, Lund, Sweden) was used as a comparator product. Patients inhaled from each device with maximal or sub-maximal inspiratory effort: Monodose inhaler 90 vs 45 l/min; Turbuhaler DPI 60 vs 30 l/min. The formulations were radiolabelled with (99m)Tc, and deposition of budesonide was quantified by gamma scintigraphy. Mean (SD) whole lung deposition for the Monodose inhaler (% capsule dose), was independent of inspiratory effort (maximal: 21.4 (4.3)%; sub-maximal: 21.4 (7.5)%), while lung deposition for the Turbuhaler DPI (% metered dose) fell significantly with decreasing inspiratory effort (maximal: 25.1 (6.1)%; sub-maximal: 18.5 (6.5)%; P<0.05). The plasma concentrations of budesonide showed the same trends as the whole lung deposition data. The Monodose inhaler showed inspiratory effort-independent drug delivery characteristics, and could prove be a valuable low-cost alternative to more complex devices such as the Turbuhaler DPI. The Monodose inhaler may be especially useful in groups of patients unable to inhale maximally through DPIs, including young children and adult patients with severe respiratory impairment.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aerosols; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Isotope Labeling; Male; Metered Dose Inhalers; Middle Aged; Radioimmunodetection; Randomized Controlled Trials as Topic; Technetium; Tissue Distribution

The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies, mostly using fibreoptic bronchoscopy on small numbers of subjects, have emphasised the similarities between different clinical phenotypes.. Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1-3 of the British Thoracic Society (BTS) guidelines. A subgroup of 49 patients treated with as required beta(2) agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 micro g twice daily.. There was considerable heterogeneity in induced sputum cell counts, particularly in non-atopic patients. A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range (>65.3%) and a normal sputum eosinophil count (<1.9%). These patients were older, predominantly female, and were more likely to be non-atopic but otherwise had similar clinical and physiological features to the group as a whole. Among the 49 subjects studied before and after inhaled budesonide, 11 patients had an isolated sputum neutrophilia. Following treatment, these patients showed significantly less improvement in visual analogue symptom scores (-5.5 v -19.4 mm; mean difference 13.9; 95% CI 0.7 to 27.0), forced expiratory volume in 1 second (FEV(1)) (-0.08 v 0.13 l; mean difference 0.21; 95% CI 0.03 to 0.39), and concentration of methacholine provoking a fall in FEV(1) of 20% or more (PC(20)) (0.15 v 1.29 doubling doses; mean difference 1.11; 95% CI 0.13 to 2.15) than the remaining 38 patients.. These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Topical; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Eosinophilia; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation; Leukocytosis; Male; Sputum; Treatment Outcome; Vital Capacity

Dose dependent anti-inflammatory effects of inhaled corticosteroids in asthma are difficult to demonstrate in clinical practice. The anti-inflammatory effect of low dose inhaled budesonide on non-invasive exhaled markers of inflammation and oxidative stress were assessed in patients with mild asthma.. 28 patients entered a double blind, placebo controlled, parallel group study and were randomly given either 100 or 400 micro g budesonide or placebo once daily, inhaled from a dry powder inhaler (Turbohaler), for 3 weeks followed by 1 week without treatment. Exhaled nitric oxide (NO), exhaled carbon monoxide (CO), nitrite/nitrate, S-nitrosothiols, and 8-isoprostanes in exhaled breath condensate were measured four times during weeks 1 and 4, and once a week during weeks 2 and 3.. A dose-dependent speed of onset and cessation of action of budesonide was seen on exhaled NO and asthma symptoms. Treatment with 400 micro g/day reduced exhaled NO faster (-2.06 (0.37) ppb/day) than 100 micro g/day (-0.51 (0.35) ppb/day; p<0.01). The mean difference between the effect of 100 and 400 micro g budesonide was -1.55 ppb/day (95% CI -2.50 to -0.60). Pretreatment NO levels were positively related to the subsequent speed of reduction during the first 3-5 days of treatment. Faster recovery of exhaled NO was seen after stopping treatment with budesonide 400 micro g/day (1.89 (1.43) ppb/day) than 100 micro g/day (0.49 (0.34) ppb/day, p<0.01). The mean difference between the effect of 100 and 400 micro g budesonide was 1.40 ppb/day (95% CI -0.49 to 2.31). Symptom improvement was dose-dependent, although symptoms returned faster in patients treated with 400 micro g/day. A significant reduction in exhaled nitrite/nitrate and S-nitrosothiols after budesonide treatment was not dose-dependent. There were no significant changes in exhaled CO or 8-isoprostanes in breath condensate.. Measurement of exhaled NO levels can indicate a dose-dependent onset and cessation of anti-inflammatory action of inhaled corticosteroids in patients with mild asthma.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Carbon Monoxide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Isoprostanes; Male; Nebulizers and Vaporizers; Nitrates; Nitric Oxide; S-Nitrosothiols

The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Humans; Male; Peak Expiratory Flow Rate; Treatment Outcome

The aim of this prospective, self-controlled, single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids (ICS) on fractional exhaled nitric oxide (FENO) in asthmatic children. Thirty-five children (age 11.2+/-0.4 yrs (mean+/-SEM)) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENO > 20 parts per billion (ppb) were included. The patients were randomly assigned to two groups: 17 patients continued ICS (group C) and 18 had montelukast added to ICS for 3 weeks (group M). FENO measurements were performed in both groups at baseline (T1) and after 3 weeks (T2), and in group M also after 2 weeks of washout. FENO was measured by a chemiluminescence analyser using an on-line method (50 mL x s(-1)) with nitric oxide-free air. The overall mean daily dose of ICS was equivalent to 530+/-58 microg x day(-1) of beclomethasone in group M and to 564+/-55 microg x day(-1) of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second (FEV1) between the two groups. After 3 weeks there was a significant reduction of FENO values in patients of group M (T1 52.2+/-7.8 ppb, T2 36.1+/-4.6 ppb) but no significant changes in group C (T1 43.5+/-6.0 ppb, T2 47.8+/-9.4 ppb). In group M after 2 weeks of montelukast withdrawal, FENO rose to baseline values (55.6+/-8.7 ppb). In conclusion, after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids. This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Budesonide; Child; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Nitric Oxide; Prospective Studies; Quinolines; Single-Blind Method; Sulfides

The present study demonstrates the equivalent efficacy for BDP 500 microg bid given via MDI with the new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma) compared to a conventional CFC propellant (Becotide, Allen & Hanburys, UK). One hundred and sixteen adult patients with stable mild to moderate asthma (FEV1 > or = 60% of predicted normal) entered a 2-week run-in period where they maintained their own inhaled corticosteroids and were then assigned to a 12-week treatment with the test drug in a randomized, multicentre, double-blind, double-dummy, parallel-group design. Ninety-one patients completed the study period. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of daytime and nighttime asthma attacks, number of nighttime awakenings, and clinical symptoms were recorded daily by patients on a diary card. Pulmonary function tests (FEV1, FVC, PEFR, MEF50 and FEF25) were completed at study entry, at the start of treatment and every 2 weeks thereafter. Morning (08.00-10.00 AM) serum cortisol was measured at the start and at the end of treatment. Adverse events were collected for the total study period. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1 (the 95% CI of the treatments' difference was within the 5% of the LSM of BDP CFC). The other secondary pulmonary function tests measured at the clinic visit showed a satisfactory asthma control, albeit without statistically significant differences between groups. Decreases in the use of rescue salbutamol and in clinical symptoms were also reported in both groups, with no differences between them. Adverse events were reported in 81.4% of patients in the BDP HFA group and in 82.5% in the CFC group. There were 73 and 59 adverse drug reactions in the two groups, respectively; the difference was mainly due to differences in taste. No drug-related serious adverse events were reported in either group. No difference was seen for morning serum cortisol between baseline and end of treatment, or between groups. In conclusion, the BDP-HFA 134a formulation proved to be statistically equivalent to the standard BDP CFC product over 12 weeks in adult patients with mild to moderate asthma.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Least-Squares Analysis; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome; United Kingdom; Vital Capacity

In this randomized controlled economic evaluation we compared guided asthma self-management with usual asthma care according to guidelines for Dutch family physicians. Nineteen family practices were randomized, and 193 adults with stable asthma (98 self-management, 95 usual care) were included and monitored for 2 years. We hypothesized that introducing self-management would not compromise asthma control and cost would be equal to or lower than in usual care. Patient-specific cost data were collected, preference-based utilities were assessed, and incremental cost per quality-adjusted life year (QALY) and successfully treated week gained was calculated. Self-management patients gained 0.039 QALY (95% confidence interval [CI], 0.003 to 0.075) and experienced 81 (95% CI, 78 to 84) successfully treated weeks in 2 years' time; the corresponding figures for usual care were 0.024 (95% CI, -0.022 to 0.071) and 75 (95% CI, 72 to 78). Total costs were 1,084 euros(95% CI, 938 to 1,228) for self-management and 1,097 euros (95% CI, 933 to 1,260) for usual care. Self-management patients consumed 1,680 (95% CI, 1,538 to 1,822) puffs of budesonide, usual care patients 1,897 (95% CI, 1,679 to 2,115). Mean productivity cost due to limited activity days was 213 euros lower among self-management patients. When all costs were included, self-management was cost-effective on all outcomes. The probability that self-management was cost-effective relative to usual care in terms of QALYs was 52%. We conclude that guided self-management is a safe and efficient alternative approach compared with asthma treatment usually provided in Dutch primary care.

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Family Practice; Female; Forced Expiratory Volume; Glucocorticoids; Health Care Costs; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Netherlands; Patient Education as Topic; Peak Expiratory Flow Rate; Quality-Adjusted Life Years; Self Care

Inhaled corticosteroids are effective antiinflammatory therapy for asthma; however, they do not completely abolish allergen-induced airway inflammation. Leukotriene modifiers attenuate both early and late allergen responses and have antiinflammatory properties. We reasoned that treatment with budesonide and montelukast in combination might provide greater antiinflammatory effects than either drug alone, and the purpose of this study was to compare the effects of treatment with budesonide and montelukast, alone or in combination, on outcome variables after allergen inhalation. Ten subjects with asthma with dual responses after allergen inhalation were included in this randomized, double-blind, crossover study. Outcomes included early and late asthmatic responses, and changes in airway responsiveness and sputum eosinophilia, measured before and after challenge. Treatment with montelukast attenuated the maximal early asthmatic response compared with placebo (p < 0.001) and budesonide (p = 0.002). Both budesonide and montelukast, alone and in combination, attenuated the maximal late asthmatic response compared with placebo (p < 0.01). Budesonide and montelukast, alone and in combination, afforded protection against allergen-induced airway hyperresponsiveness (p < 0.05), although the treatment effect of budesonide was greater than that of montelukast (p < 0.05). Treatment with budesonide and montelukast, alone and in combination, also attenuated allergen-induced sputum eosinophilia. Thus, montelukast and budesonide attenuated allergen-induced asthmatic responses, airway hyperresponsiveness, and sputum eosinophilia, although combination treatment did not provide greater antiinflammatory effects than either drug alone.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Humans; Inflammation; Leukotriene Antagonists; Prospective Studies; Quinolines; Respiratory Hypersensitivity; Respiratory System; Sulfides

The aim of this study was to compare the efficacy safety and cost of Seretide (salmeterol/fluticasone propionate (Salm/FP), 50/250 microg bd) via Diskus with formoterol (Form; 12 microg bd) and budesonide (Bud; 800 microg bd) given concurrently (Form+Bud) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy. The study used a randomised, double-blind, double-dummy, parallel-group design, consisting of a 2-week run-in period on current corticosteroid therapy (1000-1600 microg/day of BDP or equivalent) and a 12-week treatment period. Symptomatic patients (n = 428) with FEV1 of 50-85% predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP (50/250 microg bd) via a single Diskus inhaleror Form+Bud (12+800 microg bd) via separate Turbuhalers. Clinic, diary card and asthma-related health-care resource utilisation data were collected. Improvement in mean morning peak expiratory flow (PEFam was similar in the Salm/FP and Form+Bud groups. Both PEFam and mean evening PEF (PEFpm) increased by a clinically significant amount (>20 L/min) from baseline in both treatment groups. The mean rate of exacerbations (mild, moderate or severe) was significantly lower in the Salm/FP group (0.472) compared with the Form+Bud group (0.735) (ratio = 0.64; P < 0.001), despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group. Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms, with a higher median percentage of symptom-free nights (P = 0.04), nights with a symptom score <2 (P = 0.03), and nights with no awakenings (P = 0.02). Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group (P<0.05). Both treatments were well tolerated, with a similar low incidence of adverse events. This study showed that in symptomatic patients with moderate-to-severe asthma, Salm/FP (50/250 microg bd), administered in a single convenient device (Diskus), was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud (800 microg bd) given concurrently with Form (12 microg bd) in terms of improvement in PEFam, and superior at reducing exacerbations and nights with symptoms or night-time awakenings. Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Sleep

There is a need for easily measurable markers of airway inflammation to guide the use of anti-inflammatory treatment in asthma. Eosinophilic cationic protein (ECP) levels in sputum and blood correlate with clinical severity, and serial measurements of ECP have been proposed as a suitable candidate.. Our aim was to confirm that sputum and serum ECP measurements would provide a more sensitive indicator of responses to asthma treatment than eosinophil counts per se, in a randomized, placebo-controlled, crossover study of terbutaline, budesonide, and their combination in patients with chronic persistent asthma. We compared the changes in eosinophil counts and ECP in induced sputum and blood during each treatment period.. Budesonide and combined treatment caused a significant reduction in sputum eosinophils (-2.7% and -2.3%, respectively, P < 0.05). Sputum eosinophils increased with terbutaline (+3.9%, P = 0.049). In contrast, the changes for sputum ECP were not significant. There was a similar treatment effect on blood eosinophils, but not for serum ECP. Correlations between sputum and blood eosinophils were significant with and without budesonide, but were nonsignificant between sputum and blood ECP during the active treatments. Correlations between sputum eosinophils and ECP, and between blood eosinophils and serum ECP were greatest during treatment with placebo or terbutaline alone: budesonide weakened or abolished these relationships.. Compared with eosinophil counts, ECP measurements in either induced sputum or serum failed to reflect treatment-related changes in chronic asthma. We conclude that ECP is not a sensitive or reliable means of evaluating airway inflammation, and can not be recommended for assessing responses to anti-inflammatory therapy.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchodilator Agents; Budesonide; Eosinophil Granule Proteins; Eosinophils; Female; Glucocorticoids; Humans; Inflammation Mediators; Male; Middle Aged; Ribonucleases; Sputum; Terbutaline; Treatment Outcome

To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer, i.e. a multidose dry powder inhaler, or by the Pulmicort Turbuhaler in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment.. A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV(1)), need for anti-inflammatory therapy, inhalation of beta(2)-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 microg salbutamol. Primary variable was FEV(1), secondary were other pulmonary function test variables, PC(20)FEV(1) for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables.. The comparison of the FEV(1) at study endpoint indicated that the Novolizer was at least as efficacious as the Turbuhaler (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups.. The budesonide Novolizer is therapeutically equivalent to the Pulmicort Turbuhaler for the long-term treatment of patients with mild to moderate persistent asthma.

Topics: Adolescent; Adult; Aged; Asthma; Budesonide; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Middle Aged; Therapeutic Equivalency

Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out.. We compared changes in AHR to inhaled methacholine and adenosine 5'-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment.. In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV(1) (PC(20)). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC(20) methacholine, PC(20) AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks.. Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 +/- 0.3 doubling doses for methacholine and by 2.6 +/- 0.5 doubling doses for AMP. These changes were significantly different from each other (P =.003). Significant variation in PC(20) methacholine (P <.05) value, PC(20) AMP (P <.001) value, percentage of sputum eosinophils (P <.001), and percentage of sputum epithelial cells (P <.001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC(20) AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 +/- 0.3, 2.2 +/- 0.3, and 2.8 +/- 0.3 doubling doses of PC(20) AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment.. The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.

Topics: Adenosine Monophosphate; Adult; Asthma; Bronchial Hyperreactivity; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Sputum

In a recent placebo-controlled study in mild atopic asthmatics, we observed a significant decrease in eosinophils in the bronchial submucosa, after 2 months oftreatment with inhaled formoterol and budesonide. Biopsy material from each treatment group; formoterol (24 microg bid), budesonide (400 microg b. i. d.) and placebo has been further assessed to investigatethe role of Th-2 cytokines by immunohistochemistry using Mabs to eosinophils as an index of inflammation, IL-4 and IL-5. Treatment with formoterol significantly reduced the number of eosinophils (EG2+) in the submucosa and epithelium, but this was not paralleled by changes in cytokine immunoreactivity In contrast, treatment with budesonide significantly reduced both the number of eosinophils (EG2+) and immunoreactivity for IL-4 and IL-5 in the submucosa. Thus, while budesonide has effects on cytokines involved in eosinophil recruitmentthis explanation does not apply tothe eosinopaenia observed with the long-acting beta2 adrenoreceptor agonist formoterol.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchoscopy; Budesonide; Cytokines; Double-Blind Method; Drug Therapy, Combination; Eosinophilia; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Interleukin-4; Interleukin-5; Male; Statistics, Nonparametric; Th2 Cells

Measurement of health-related quality of life (HR-QOL) may show benefits of asthma treatments not revealed by objective monitoring and can complement clinical and physiological assessments of treatment outcome. HR-QOL was measured in four countries in a multicenter, double-blind, randomized comparison of salmeterol/fluticasone propionate combination and budesonide in patients aged > or =12 years with moderate-to-severe asthma uncontrolled by inhaled corticosteroids.. Patients received, twice daily, either salmeterol/fluticasone propionate 50/250 microg (Seretide/ Advair) via Diskus inhaler (n = 55) or budesonide 800 microg (Pulmicort) via Turbuhaler (n = 58). Patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 12 weeks treatment (or early withdrawal). The analysis included 113 patients.. Mean improvement in AQLQ scores achieved clinical importance in all four domains in the salmeterol/fluticasone group (AQLQ change > or =0.5), but in only two domains in the budesonide group. Although the mean overall improvement in AQLQ scores observed in the salmeterol/fluticasone group was significantly greater than that observed in the budesonide group (difference of 0.45; p = 0.002), the difference was less than the minimal important difference (0.5). Nevertheless, further analysis showed that the number-needed-to-treat was only 3.4. This indicates that only 3.4 patients need to be treated with the salmeterol/fluticasone combination for one patient to experience a meaningful improvement in HR-QOL, relative to monotherapy with an increased dose of budesonide.. Treatment of moderate-to-severe asthma with salmeterol/fluticasone propionate resulted in superior gains in HR-QOL relative to increasing the dose of inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires

The perception of bronchoconstriction may be modulated by airway inflammation. However, the effect of inhaled corticosteroid (ICS) treatment on perception in subjects with asthma has received limited study. The aim of this study was to determine the effect of inhaled budesonide on the perception of breathlessness induced by histamine challenge. Thirty-five subjects with poorly controlled asthma were randomized to receive budesonide (1,600 or 3,200 microg/d) for 8 wk, followed by 8 wk at 1,600 microg/d and subsequent downtitration according to a clinical algorithm. Borg scores were recorded during histamine challenges performed at baseline and at 8, 16, 24, 48, and 72 wk. Perception was estimated as the slope of Borg/% fall FEV(1). The Borg/FEV(1) slope increased significantly after 8 wk of budesonide (0.09 [0.08-0.12] to 0.15 [0.11-0.19], p = 0.002), and remained increased compared with baseline values at all subsequent visits. There were no significant differences in Borg/ FEV(1) slope between subjects who were and were not taking ICS at study entry. The magnitude of change in the Borg/FEV(1) slope did not differ significantly between treatment groups and was not related to changes in baseline FEV(1), airway hyperresponsiveness, blood eosinophils, or serum eosinophil cationic protein (ECP). We conclude that treatment with budesonide enhances the perception of airway narrowing, but the effect is unrelated to budesonide dose, or to changes in circulating eosinophil markers.

Topics: Administration, Inhalation; Adolescent; Adult; Algorithms; Asthma; Attitude to Health; Blood Proteins; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Dyspnea; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Regression Analysis; Ribonucleases; Severity of Illness Index; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Drug Administration Schedule; Electronic Data Processing; Humans; Lung; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Self Care; Spirometry

To study the systemic activity of inhaled steroids in young children.. Forty children with mild asthma aged 1 to 3 years were studied in a 3-way crossover, randomized, placebo-controlled, double-blind trial. Treatment with inhaled fluticasone propionate, 200 microg twice daily delivered via pressurized metered-dose inhaler (pMDI) and Babyhaler (FP400), was compared with budesonide, 200 microg twice daily delivered via pMDI and NebuChamber (BUD400), and to placebo. The Babyhaler was primed before use. Knemometry was used to detect systemic steroid activity. It was performed with a hand-held knemometer after 1 and 4 weeks of treatment. The increase in lower-leg length within this 3-week period was used as the outcome measure. The intention-to-treat population was analyzed by analysis of variance.. The increases in the lower-leg length during placebo, BUD400, and FP400 treatments were 85, 45, and 34 microm/d, respectively (adjusted mean). The growth in lower-leg length was significantly reduced from both steroid treatments. The difference between BUD400 and placebo was -40 microm/d (n = 25; 95% confidence interval [CI]: -8 to -72). The difference between FP400 and placebo was -51 microm/d (n = 26; 95% CI: -19 to -83). The difference between FP and BUD was -11 microm/d and was not statistically significant (n = 28; 95% CI: 20 to -42).. FP and BUD are both systemically active in children 1 to 3 years old when administered for 4 weeks from their dedicated spacer devices in daily doses of 400 microg with no difference between the 2 steroid regimens. These findings call for studies of clinical side effects from these treatments of preschool children.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Double-Blind Method; Fluticasone; Growth; Humans; Infant; Leg; Nebulizers and Vaporizers

This 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of budesonide 400 microg administered once daily via Turbuhaler in adults previously treated with at least twice-daily dosing of inhaled corticosteroids. Pulmonary function (FEV1, PEF, FVC, FEF(25-75%)), asthma symptom scores, quality of life, and breakthrough medication use were significantly (p < 0.05) different in patients receiving once-daily budesonide Turbuhaler compared to placebo, and significantly (p < 0.001) more patients receiving placebo discontinued the study. Adverse events were similar between study groups. Once-daily administration of budesonide Turbuhaler was safe and efficacious in patients previously treated with inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Nebulizers and Vaporizers; Powders

Recovery from an asthma exacerbation may take days or weeks even after the introduction of appropriate exacerbation therapy. However airway responsiveness and sputum eosinophils can be reduced within 6 hours by a single dose of inhaled corticosteroids.. To determine if a single dose of 3200 microg of budesonide increases the rate of recovery from an asthma exacerbation.. Nineteen asthmatic subjects with an asthma exacerbation following withdrawal of inhaled corticosteroids were randomised to receive either usual care (doubling their dose of inhaled corticosteroids) plus placebo or usual care plus a single dose of 3200 microg of budesonide in a double-blind manner. Subjects monitored peak flow (PEF), symptoms, and beta agonist use daily for four weeks. The lowest PEF reading for each week was calculated as a percentage of the best peak flow value achieved in the recent past (PEF lowest % best).. In the first week following exacerbation, PEF (lowest % best) was significantly greater in the budesonide group than in the placebo group (87.4 +/- 4.7 vs. 76.7 +/- 5.3; p = 0.029). However in the fourth week following exacerbation PEF was not significantly different (p = 0.728). The proportion of subjects who had a symptom free day during the first week was significantly higher in the budesonide group (p = 0.0012).. A single high dose of inhaled corticosteroids added to usual exacerbation treatment might increase the rate of recovery from a mild exacerbation of asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Severity of Illness Index

The initial 12-week, double-blind phases of three studies demonstrated that budesonide inhalation suspension (BIS) is effective and well tolerated in infants and young children (6 months to 8 years of age) with persistent asthma.. Open-label, 52-week extensions to these studies were conducted to evaluate long-term safety of BIS, including effects of treatment with the lowest effective dose of BIS on hypothalamic-pituitary-adrenal (HPA)-axis function, as compared with conventional asthma therapy (CAT). Complete results of the earlier phases of the studies and of long-term safety are reported elsewhere; only results pertaining to HPA-axis function are summarized here.. Patients eligible for the open-label phases of the three trials were randomized to treatment with nebulized BIS (n = 447) or CAT (n = 223). CAT included short-acting oral or inhaled beta2-agonists, methylxanthines, or cromolyn sodium; in two of the studies, CAT could have included other inhaled corticosteroids. HPA-axis function, which had been evaluated during the 12-week double-blind studies, was again evaluated at the beginning and end of the 52-week study period using basal plasma cortisol concentrations and response to stimulation with a 250-microg dose of adrenocorticotropic hormone.. There was no evidence of altered HPA-axis function attributable to BIS treatment. No clinically or statistically significant differences in basal or adrenocorticotropic hormone-stimulated plasma cortisol concentrations were observed between BIS and CAT in either the 12-week, double-blind or 52-week, open-label phases of the three studies.. The results indicate that treatment with BIS does not result in clinically significant suppression of HPA-axis function in infants and young children.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Hypothalamo-Hypophyseal System; Infant; Male; Pituitary-Adrenal System; Suspensions

The availability of antiinflammatory asthma medications for infants and young children has been limited. The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma.. We conducted a randomized, parallel-group, 52-week, open-label study in 36 US clinical sites. Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication; 287 children (86%) completed the study. Patients received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed by dose titration at the investigator's discretion. The main outcome measure was the rate of asthma exacerbations over 52 weeks. Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy, asthma symptom scores, rescue medication use, and health care resource use.. The budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per year compared with 2.41 (1.85) for the cromolyn group, significantly longer times to first exacerbation and first use of additional long-term asthma medication, greater improvements in asthma symptom scores, reduced use of rescue medication, and fewer urgent care visits. Both treatments were well tolerated.. Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma. Both treatments were well tolerated with similar adverse event profiles.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Female; Health Services; Humans; Life Tables; Male; Nebulizers and Vaporizers; Suspensions; Treatment Outcome

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks. There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group. Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Equipment Safety; Female; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate; Statistics, Nonparametric

In the treatment of asthma, inhaled steroids are more effective than cromolyn, whereas the latter offers extreme safety. The aim of the present pilot study was to evaluate, contemporarily, efficacy and safety aspects of different asthma treatment modalities. In 75 school-age children (mean age 9.5 years; range 5.5-14.7 years), treatment of asthma was started with budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromones (CROM, n = 15). BUD was used at a dose of 800 microg/day during the first 2 months and at 400 microg/day thereafter. The respective FP doses were 500 and 200 microg/day. Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second (FEV1) and by evaluating the use of bronchodilators. Side-effects of the treatment were evaluated by following growth of the children and by performing low-dose adrenocorticotropin (ACTH) testing. At 4 months FEV1 had improved by a mean of 8.2% in the BUD group and by 5.4% in the FP group (p< 0.01 vs. baseline in both groups; NS between BUD and FP groups). The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group (p< 0.05), and from three doses/week to one dose/week in the FP group (p< 0.01) (NS between the groups). In the CROM group, the FEV1 value and the use of bronchodilators did not change. The treatment was unsuccessful on the basis of FEV1 decrease and increased bronchodilator use in, respectively, 30 and 15% of the BUD-, 20 and 7% of the FP-, and 50 and 47% of the CROM-treated children. Therefore, to prevent one treatment failure in the CROM group, between three and five children would need to move to treatment with steroids. The treatment had measurable systemic effects on the basis of height standard deviation (SD) score decrease and minor adrenocortical suppression in, respectively, 60 and 30% of the BUD-, 27 and 17% of the FP-, and 20 and 0% of the CROM-treated children. Therefore, to avoid systemic effects in one steroid-treated child, three BUD- and six to 14 FP-treated children would need to move to treatment with CROM. In conclusion, in school-age children asthma should be treated first with inhaled steroids. It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Cromolyn Sodium; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Pilot Projects; Treatment Outcome

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Probability; Reference Values; Single-Blind Method; Treatment Outcome; Triamcinolone

To assess the long-term safety of hydrofluoroalkane 134a (HFA)-beclomethasone dipropionate (BDP) extrafine aerosol administered by the Autohaler compared with chlorofluorocarbon (CFC)-BDP administered by a press-and-breathe metered-dose inhaler (pMDI) and spacer (+S) in the treatment of children with asthma.. This 12-month, open-label, randomized, multicenter study enrolled 300 children who were aged 5 to 11 years and had well-controlled asthma on inhaled CFC-BDP or budesonide; 256 patients were using doses within the recommended range (200-400 microg) and were analyzed separately. Patients were randomized in a 1:3 ratio to continue on CFC-BDP+S at approximately the same dose as they were using before study entry or switch to HFA-BDP at half the daily dose.. Asthma control was well maintained in the HFA-BDP group as evidenced by lung function tests and asthma symptoms compared with CFC-BDP+S at approximately twice the dose. There were no significant differences between the HFA-BDP 100 to 200 microg and CFC-BDP+S 200 to 400 microg treatment groups in mean change from baseline in height (5.23 cm vs 5.66 cm at month 12, respectively) or mean growth velocity from day 1 to month 12 (5.27 cm/y vs 5.71 cm/y, respectively). There were no significant differences between groups in adrenal function tests or markers of bone metabolism.. In this long-term study in children with asthma, extrafine HFA-BDP provided long-term maintenance of asthma control at approximately half the dose compared with CFC-BDP+S. There were no clinically meaningful differences between HFA-BDP extrafine aerosol and conventional CFC-BDP+S with regard to growth or other systemic effects.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Child; Child Development; Child, Preschool; Chlorofluorocarbons; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Growth; Humans; Hydrocarbons, Fluorinated; Male; Respiratory Function Tests; Treatment Outcome

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler, 200 microg once every night (q.n.), 100 microg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler, 200 microg, q.n. without loss of asthma control.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Severity of Illness Index

A retrospective analysis, based on a randomized, placebo-controlled, 12-week study in children 6 months to 8 years of age with persistent asthma, was performed to compare the efficacy and safety of budesonide inhalation suspension 0.25 mg and 0.5 mg twice daily vs. placebo in children < 4 and > or = 4 years of age. Both age groups demonstrated significant (p < or = 0.050) improvement in nighttime and daytime asthma symptom scores and decreased bronchodilator use compared with placebo. In addition, the safety profile of twice-daily budesonide inhalation suspension was favorable in both age groups.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Drug Administration Schedule; Female; Humans; Infant; Male; Randomized Controlled Trials as Topic; Retrospective Studies

Combinations of inhaled glucocorticoids and long-acting beta2-agonists in the same inhaler device have become available in recent years. In this double-blind, randomized, placebo-controlled and crossover study we have evaluated the onset of action of budesonide and formoterol in a single inhaler (Symbicort Turbuhaler) and that of the fixed combination of salmeterol and fluticasone (Seretide Diskus). Thirty patients with a mean FEV1 of 2.54 l (range: 1.48-4.28) and a mean inclusion reversibility in FEV1 of 19.1% were included. Single doses of budesonide/formoterol 160/4.5 microg and 2x (160/4.5) microg, salmeterol/fluticasone 50/250 microg, or placebo were given. Serial measurements of FEV1 were performed over 3 h. The combination of one or two inhalations of budesonide/formoterol showed a faster onset of action than salmeterol/fluticasone, both evaluated as mean FEV1 at 3 min (2.74, 2.75 and 2.56 l respectively P<0.001 for both doses of budesonide/formoterol), or as average FEV1 from 0 to 15 min (2.80, 2.83 and 2.67 l respectively P<0.001 for both doses of budesonide/formoterol). For placebo, mean FEV1 at 3 min was 2.46 l, and the average FEV1 at 0-15 min was 2.50 l. Furthermore, budesonide/formoterol at both doses resulted in higher FEV1 than salmeterol/fluticasone at 3 h. We conclude that the combination of budesonide/formoterol has a faster onset of action than salmeterol/fluticasone.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Spirometry; Treatment Outcome

The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers.. Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed.. At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.. When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Powders

Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing, suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma. This study aimed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma, and to examine whether the mechanism of clearance of eosinophils was by apoptosis. A randomized, double-blind, placebo-controlled, crossover study was conducted. At the screening visit, adults with stable asthma (n = 41) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia (> or = 7%) were randomized (n = 26) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler, on two separate study days. Symptoms and lung function were followed for 6 h, then sputum was induced and airway responsiveness to hypertonic saline determined. Sputum eosinophils (mean, SE) were significantly lower 6 h after budesonide (25%, 4.5), compared with placebo (37%, 6.2, p < 0.05). There was a 2.2-fold (95% CI 1.45 to 3.33) improvement in airway responsiveness with budesonide. No significant difference was seen on mast cells, apoptotic eosinophils, symptoms, or lung function. In conclusion, a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing. This may be clinically useful as therapy during mild exacerbations of asthma.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Apoptosis; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Glucocorticoids; Humans; Male; Middle Aged; Sputum

Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.. Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.. Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.. In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Osteocalcin; Peak Expiratory Flow Rate; Prospective Studies; Regression Analysis; Treatment Outcome

The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI.. Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials.. At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated.. Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Consumer Product Safety; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Statistics, Nonparametric

International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis.. To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children.. Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated.. The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively).. Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Female; Humans; Male; Methylprednisolone; Respiratory Function Tests; Sympathomimetics; Terbutaline

Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol breath-actuated inhaler (Qvar Autohaler; BDP-AH) provides an alternative to chlorofluorocarbon metered dose inhalers or dry powder inhalers (DPIs). The aim of this six-week, open-label study was to determine whether BDP-AH demonstrates equivalent asthma control to twice the dose of budesonide (BUD)-DPI (Pulmicort Turbuhaler). Adults with symptomatic asthma inadequately controlled on BUD-DPI 400 micrograms/day and beta-agonist were enrolled. Patients (n = 193) were randomised to receive 400 micrograms/day BDP-AH (n = 98) (two puffs of 100 micrograms/actuation inhaler twice daily) or 800 micrograms/day BUD-DPI (n = 95) (two puffs of 200 micrograms/actuation inhaler twice daily). Both groups showed a statistically significant change from baseline in morning (a.m.) peak expiratory flow (PEF) at weeks 5-6 (p < 0.01), indicating study treatment improved a.m. PEF over prestudy 400 micrograms/day BUD. Changes from baseline in a.m. PEF at weeks 5-6 were 15.9 l/min for BDP-AH and 14.2 l/min for BUD-DPI; the groups were statistically equivalent (90% CI -7.02-10.44; p < -0.001 [equivalence = within +/- 25 l/min]). Other efficacy assessments (evening PEF, FEV1, asthma symptoms, beta-agonist use) confirmed the treatments were clinically equivalent. Thirty-nine (40%) patients on BDP-AH and 35 (37%) on BUD-DPI experienced at least one adverse event (p = 0.767). Four (4%) patients on BDP-AH and 3 (3%) on BUD-DPI reported increased asthma symptoms. BDP-AH at half the daily dose provided equivalent asthma control to BUD-DPI; both treatments were well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Peak Expiratory Flow Rate; Sleep; Vital Capacity

We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma.. In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily.. After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety.. Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Budesonide; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Predictive Value of Tests; Quality of Life; Quinolines; Sulfides; Treatment Outcome

Markers of airway inflammation are needed for prediction of asthma deterioration and evaluation of disease severity. Few studies have focused on the dynamics of airway inflammation as reflected by the activity of the eosinophils and their proteins after withdrawal of inhaled corticosteroids.. Our goal was to investigate the effect of withdrawal of inhaled budesonide on eosinophil count in blood and eosinophil proteins in serum and urine and to relate the levels of these markers to the risk of symptoms of asthma, increased bronchial hyperresponsiveness, and deterioration of lung function.. Thirty-three children were randomly selected to continue or discontinue use of inhaled budesonide in a double-blind, placebo-controlled study. They were followed up for 4 months with regular analysis of blood, serum, and urine samples; lung function; and methacholine challenges. Eosinophil activity markers were analyzed. Age-matched healthy children provided reference data for all parameters measured.. The eosinophil number in blood and eosinophil protein levels in serum (serum eosinophil cationic protein [ECP] and serum eosinophil peroxidase [EPO]) increased significantly in the withdrawal group, and the difference between the groups was significant (P =.02 for all). Twenty-nine percent of the children in the withdrawal group remained symptom free. This subgroup had eosinophil counts at baseline below 350/microL, a serum ECP level below 15 microg/L, and a serum EPO level below 25 microg/L, each of which was related to a low risk of exacerbation (relative risk = 0.37, 0.48, and 0.37 respectively; P <.05 for all). All eosinophil markers were lower in the healthy children than in the symptom-free children with asthma.. Our data indicate that eosinophil count and/or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma.

Topics: Adolescent; Anti-Asthmatic Agents; Antigens, CD; Asthma; Biomarkers; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Child; Disease Progression; Double-Blind Method; Eosinophil Granule Proteins; Eosinophil Peroxidase; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation; Leukocyte Count; Male; Membrane Glycoproteins; Methacholine Chloride; Peroxidase; Peroxidases; Ribonucleases; Skin Tests; Spirometry; Tetraspanin 29

Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy.. To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma.. A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms.. There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms.. Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.

Topics: Acetates; Administration, Oral; Administration, Topical; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Budesonide; Confidence Intervals; Cross-Over Studies; Cyclopropanes; Humans; Quinolines; Rhinitis, Allergic, Seasonal; Single-Blind Method; Sulfides

Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma.. To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial.. Health economics were evaluated in 138 children, ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months; budesonide 400 microg/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment.. In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195; US $487; Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication.. A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Cost of Illness; Cost-Benefit Analysis; Cromolyn Sodium; Drug Costs; Female; Hospital Costs; Hospitalization; Humans; Male; Regression Analysis; Respiratory Function Tests; Safety; Sweden; Treatment Outcome

The Novolizer is a breath-actuated multidose dry powder inhaler that was developed as an alternative to the pressurized metered dose inhalers. The efficacy, safety and tolerability of the Novolizer has been compared with those of established inhalational devices for the delivery of salbutamol (Sultanol) in patients with chronic obstructive pulmonary disease and for the administration of budesonide (Pulmicort Turbuhaler) to patients with asthma. In both studies, improvement in forced expiratory volume in 1 s in patients who were randomly assigned to use the Novolizer was comparable with that in patients who used the established devices. Furthermore, no differences in tolerability or safety between the Novolizer and the control devices were observed. Finally, patient acceptance of the Novolizer was high, with the majority of patients who used it stating that they would use the device again.

Topics: Albuterol; Asthma; Bronchodilator Agents; Budesonide; Humans; Lung Diseases, Obstructive; Nebulizers and Vaporizers

This study was carried out in an attempt to compare the efficacy and safety of fluticasone propionate (FP) at the half dose of budesonide (BUD) and beclamethasone dipropionate (BD) in childhood asthma. Ninety-six children with moderate to severe asthma (9.6 +/- 2.17 years) whose asthma was already controlled on BUD (n = 52) or BD (n = 44) were recruited into the study. In the first part of the study (the first 12 weeks) each group was followed with three weekly lung function measurements, daily diary records, and peak expiratory flow (PEF) measurements on the initial medication. At the end of 6 weeks, drugs were switched to a half dose of FP, and the subjects were followed for another 6 weeks. Blood samples were obtained for osteocalcin and plasma cortisol levels after each treatment period. In the second part of the study, 50 patients continued to take FP at the half dose of BUD or BD for another 30 weeks. Clinic visits, including lung function and PEF measurements, were conducted every 10 weeks. After 6 weeks of FP treatment, there was a small but statistically significant decrease in FEV1 and FEF(25-75) in both groups (BUD and BD) without any significant obstruction. These mild changes in lung function measurements continued during long-term follow-up. However, there was no statistically significant further decrease in any lung function parameters while receiving FP (visits 3-8) (coefficient = -0.00751 L/day, p = 0.39 for FEF(25-75) and coefficient = -0.00910 L/sec/day, p = 0.055 for FEV1). There were no significant changes in the morning and evening PEF measurements and diurnal PEF variations after 6 weeks of treatment with FP compared with BUD and BD treatments. There were no significant changes in basal cortisol and osteocalcin levels before or after 6 weeks of FP treatment (p > 0.05). The present study concluded that, although FP at the half dose of BUD or BD seems to maintain reasonable control of the disease symptoms, a mild but significant and persistent decrease in lung function parameters may indicate that FP may not be twice as potent as BUD or BD in childhood asthma by evaluation of lung functions. This conclusion must be further verified with long-term studies.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Female; Fluticasone; Follow-Up Studies; Humans; Male; Respiratory Function Tests; Time Factors

Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma.. To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma.. In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 microg) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests.. Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P < or = 0.037) improvements over placebo also were observed in AM PEFR, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups.. Budesonide Turbuhaler 400 microg administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate

Guidelines on the use of inhaled steroids in asthma advocate that the daily dose should be chosen according to the severity of the disease. However, the question of the optimal starting dose remains to be properly addressed, as does the issue of the adjustment in dose required for a given patient. Whether a high initial dose of budesonide (800 microg b.i.d) was more efficacious than a standard dose (200 microg b.i.d) in controlling mild-to-moderate asthma was investigated, and whether the dose could be decreased, based on peak expiratory flow (PEF), symptom-score, beta2-agonist use in a double-blind, randomized, parallel-group 18-week study. One-hundred and sixty-nine patients (mean age 38 yrs, mean forced expiratory volume in one second 74% predicted) were enrolled. No difference was detected between the two groups in improvement in morning PEF (+61 L x min(-1) in the high-dose group, +60 L x min(-1) in the standard-dose group by 16 weeks). Morning and evening PEF values stabilized before the end of the first 4 weeks. No difference between groups was observed in symptom score, beta2-agonist use, number of exacerbation per interval and the best forced expiratory volume in one second achieved. The proportion of subjects being able to decrease the doses of budesonide was similar in both treatment strategies. It is concluded that both high and standard initial doses are equally effective in controlling symptoms and improving lung function in mild-to-moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Although the beneficial effects of treatment with inhaled steroids in asthma are widely accepted, the role of early intervention in patients with mild asthma remains unsettled. Conventional efficacy trials are often of short duration and involve highly selected patient populations that exclude many patients typical of those encountered in routine clinical practice. Hence, a large "real-world" effectiveness study is needed to evaluate the benefits of early intervention with inhaled steroids in patients with mild, persistent asthma. In the START (inhaled Steroid Treatment As Regular Therapy in early asthma) study, patients ages 6-60 years, from 31 countries and districts worldwide with mild persistent asthma, have been randomized to once-daily treatment with budesonide, 200 microg (for patients < 11 years) or 400 microg (for patients > or = 11 years), or placebo via Turbuhaler for 3 years. The double-blind treatment period will be followed by a 2-year period of open budesonide treatment. Throughout the study, other asthma medication including glucocorticosteroids can be given as judged appropriate by the investigator. Lung function will be measured by spirometry using standardized techniques at 3-month intervals throughout the study, and bronchodilator reversibility will be measured annually. The primary outcome measures are the time to the first severe asthma-related event during the first 3 years of the study and the change in postbronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline during the entire 5-year study period. These measures have been chosen to reflect the progression of mild asthma toward more severe asthma and the extent of irreversible airflow limitation, which should reflect the degree of airway remodeling.

Topics: Acute Disease; Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Follow-Up Studies; Glucocorticoids; Humans; Middle Aged; Multicenter Studies as Topic; Nebulizers and Vaporizers; Outcome Assessment, Health Care; Random Allocation; Randomized Controlled Trials as Topic; Research Design; Respiratory Function Tests; Sample Size; Statistics as Topic

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests; Time Factors; Treatment Outcome

High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Biomarkers; Budesonide; Chronic Disease; Contusions; Creatinine; Female; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Quality of Life

This study was conducted to investigate whether a single dose of nebulized budesonide effectively decreased airway inflammation as demonstrated by exhaled nitric oxide (eNO) levels. A single dose of nebulized budesonide, but not nebulized terbutaline, rapidly decreased eNO levels in 6 hours. The decrease in eNO levels induced by nebulized budesonide was correlated to an increase in peak expiratory flow rate.

Topics: Adolescent; Asthma; Blood Pressure; Bronchodilator Agents; Budesonide; Case-Control Studies; Child; Female; Humans; Male; Nebulizers and Vaporizers; Nitric Oxide; Peak Expiratory Flow Rate; Terbutaline

Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often delivered via a large volume spacer device, but these are bulky and inconvenient. Dry powder inhalers (DPIs) provide a highly portable and convenient propellant-free alternative to pMDIs for asthma maintenance therapy However, each DPI could have unique in vivo delivery characteristcs. In order to quantify the total and regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b) Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized cross-over study was carried out in 12 mild to moderate asthmatic patients. Deposition was quantified by the imaging technique of gamma scintigraphy Optimal inhalation techniques were used throughout. Mean (SD) whole lung deposition (% metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2) %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P < 0.01]. The regional distribution patterns in the lungs were predominantly central for all three devices. Nebuhaler reduced oropharyngeal deposition significantly compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler and hence drugs delivered by Easyhaler would be expected to have a similar clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Equipment Design; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders; Radionuclide Imaging; Statistics, Nonparametric; Technetium; Treatment Outcome; Vital Capacity

Exhaled nitric oxide (ENO) has been proposed as a marker of airway inflammation in asthma and could be useful to evaluate the response to anti-inflammatory treatment. We investigated the effect of budesonide and nedocromil sodium on ENO levels and lung function in asthmatic children. Twenty stable steroid-naïve asthmatic children were randomized in a single blind, cross-over study to receive inhaled budesonide (group A) or nedocromil sodium (group B) for 6 weeks. ENO was measured with a chemiluminescence analyser at baseline and at the end of each treatment period. Repeated-measures ANOVA was carried out. In asthmatic baseline ENO levels [mean 32.5 ppb, 95% confidence interval (CI) 26.4 to 38.7] were significantly higher compared to reference values (8.7 ppb, 95% CI 8.1 to 9.2, P<0.001). There were no treatment-order effect, no carry-over effect and in both groups the response pattern was the same: budesonide significantly lowered ENO levels from 41.0 ppb to 22.8 ppb in group A (mean, P<0.01) and from 22.6 ppb to 13.0 ppb in group B, (mean, P<0.05), while nedocromil did not reduce ENO values (from 24.4 ppb to 22.6 ppb in group B and from 22.8 ppb to 38.0 ppb in group A, mean, P = NS and P<0.01 respectively). After budesonide treatment ENO values of asthmatics were still significantly higher than in healthy children The baseline values of FEV1 and FEF(25-75) were normal in both groups and no significant changes were observed during the study. In conclusion, our study shows that budesonide, but not nedocromil sodium, significantly reduces ENO levels in stable asthmatic children even in absence of changes in the lung function.

Topics: Adolescent; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Child, Preschool; Cross-Over Studies; Female; Forced Expiratory Volume; Humans; Luminescent Measurements; Male; Maximal Midexpiratory Flow Rate; Nedocromil; Nitric Oxide; Single-Blind Method

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta(2)-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappaB), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappaB, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappaB, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappaB, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappaB-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta(2)-agonists probably operates through alternative pathways.

Topics: Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Biopsy; Bronchi; Bronchodilator Agents; Budesonide; Cytokines; Double-Blind Method; Down-Regulation; Eosinophils; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Immunohistochemistry; Male; NF-kappa B; Placebos; Time Factors; Vascular Cell Adhesion Molecule-1

Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these subjects. The regular use of inhaled corticosteroids improves BHR in patients with symptomatic asthma. The aim of this study was to determine whether BHR in adolescents with asthma remission could be reduced by prolonged treatment with inhaled corticosteroids.. A randomized, double-blind, placebo-controlled, parallel study.. Thirty-seven adolescents with BHR and long-term remission of their asthma (neither symptoms nor any medication use during the previous 2 years).. Subjects received inhaled budesonide (two 200-microg puffs bid; budesonide group, n = 19) or identical placebo (placebo group, n = 18) for 9 months. A separate group of patients with symptomatic asthma (symptomatic group, n = 19), using the same regimen of budesonide, was also studied.. The provocative concentration of methacholine producing a 20% fall in FEV(1) (PC(20)) was measured before and every 3 months during treatment. There was no significant difference among the three groups for the baseline PC(20). In neither the placebo nor the budesonide group did the geometric mean of PC(20) change significantly over the 9-month period. In contrast, a significant increase in PC(20) was noted in the symptomatic group as a result of the budesonide treatment.. Our data have shown that budesonide inhaled regularly for 9 months did not cause a significant improvement in the BHR of adolescents with long-term asthma remission. This suggests that the mechanism underlying BHR in this clinical setting may be different from that in symptomatic asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 microg/d during the first 2 months and 400 microg/d thereafter. The respective fluticasone propionate doses were 500 and 200 microg/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13-29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8-25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4-16%; P < 0.01) and 6% (95% confidence interval, 16% decrease-3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14-28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0-16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Androstadienes; Asthma; Budesonide; Child; Dehydroepiandrosterone Sulfate; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male

Both domiciliary and laboratory measures of nasal function have been used to evaluate treatment response in allergic airways disease; however, these measures have not been compared.. To determine the relationship of domiciliary measures (daily symptoms, peak inspiratory nasal flow, and nasal oral index) and laboratory measures (rhinomanometry, acoustic rhinometry) in assessing treatment response with topical steroids and specific inflammatory mediator blockage.. Twenty-one patients with seasonal allergic rhinitis and asthma were enrolled into a single-blind, placebo-controlled, crossover study comparing 2 weeks of 1) 400 microg inhaled plus 200 microg intranasal budesonide once daily and 2) 10 mg montelukast plus 10 mg cetirizine once daily. Before each treatment, patients received 7 to 10 days of placebo period. Laboratory measurements were made of nasal resistance by posterior rhinomanometry, and nasal volume between 0 and 5 cm by acoustic rhinometry after both placebo and active treatment periods. Daily domiciliary recordings were made of allergic rhinitis nasal symptoms scores and peak nasal and oral inspiratory flow rate (enabling the calculation of a nasal/oral index) throughout the study.. There were significant (P < 0.05) improvements for all allergic rhinitis symptoms with both therapies, after factoring for pollen count. Spearman's rank correlation for comparison among nasal symptoms and the objective responses were: nasal inspiratory flow rate (R = -0.50, P = 0.02); nasal/oral index (R = -0.55 P = 0.01); rhinomanometry (R = 0.24, P = 0.30); and acoustic rhinometry (R = -0.21, P = 0.36).. Both treatments were effective in managing allergic rhinitis symptoms, and patients' symptoms were more closely associated with domiciliary measurements of nasal flow than laboratory measurements of nasal function.

Topics: Acetates; Administration, Inhalation; Administration, Intranasal; Adult; Airway Resistance; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Cetirizine; Cross-Over Studies; Cyclopropanes; Female; Glucocorticoids; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Nasal Obstruction; Quinolines; Rhinitis, Allergic, Seasonal; Rhinomanometry; Rhinometry, Acoustic; Sulfides

Hydrofluoroalkane-beclomethasone dipropionate Autohaler (HFA-BDP AH) is a breath-actuated chlorofluorocarbon (CFC)-free metered dose inhaler in which BDP is in a solution of HFA propellant. Budesonide Turbuhaler (BUD TH) is a breath-dependent dry powder inhaler.. To test the hypothesis that half the daily dose of HFA-BDP AH would provide an equivalent control of asthma symptoms to the BUD TH.. This was an 8-week open study in patients with symptomatic moderate-to-severe asthma, previously on BUD 500-1,000 microg x day(-1), or an equivalent. After 5-14 days' run-in, patients were randomized to HFA-BDP AH 800 microg x day(-1) or BUD TH 1,600 microg x day(-1). The intent-to-treat population consisted of 111 patients on HFA-BDP AH and 98 patients on BUD TH.. Mean change from baseline in PEF in the morning (AM PEF) at week 8 was 23.95 liters x min(-1) for HFA-BDP AH and 24.46 liters x min(-1) for BUD TH. A two-sided equivalence test using the 0.51 liter x min(-1) difference gave 95% confidence intervals within a defined equivalence interval of (-infinity, 25 liters x min(-1)) indicating that the mean change in AM PEF was equivalent for the two groups. There were no significant differences in the mean change from baseline in FEV1 or beta-agonist use. Patients using HFA-BDP AH had a significantly greater mean change from baseline in the percentage of days free from shortness of breath (p = 0.05), chest tightness (p = 0.02) and nights without sleep disturbance (p = 0.04) at week 3, and wheeze (p = 0.01), shortness of breath (p = 0.02), chest tightness (p < 0.01) and daily asthma symptoms (p = 0.03) at week 8. The incidence, type and severity of adverse events were similar in each group. At week 8, the mean change from baseline in corrected urine cortisol/creatinine ratio in a subgroup of patients was -0.36 for HFA-BDP and -4.88 for BUD TH (p < 0.01).. HFA-BDP 800 microg x day(-1) provided control of moderate-to-severe asthma with efficacy and safety at least similar to BUD TH 1,600 microg x day(-1).

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Proteins; Budesonide; Cohort Studies; Creatinine; Eosinophil Granule Proteins; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; France; Germany; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Netherlands; Peak Expiratory Flow Rate; Respiratory Function Tests; Ribonucleases; Treatment Outcome

The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, 200 microg budesonide, or 200 microg budesonide plus 4.5 microg formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Severity of Illness Index

Budesonide is an inhaled corticosteroid with high topical potency and low systemic activity recommended in the treatment of chronic asthma.. This study was conducted to determine the efficacy and safety of inhaled budesonide via a breath-activated, multi-dose, dry-powder inhaler.. Multicenter randomized parallel-group, placebo-controlled, double-blind, clinical trial.. Multicenter study in the university units.. Adult patients with mild-to-moderate asthma that was not controlled using bronchodilator therapy alone.. Comparison of budesonide 400 microg administered twice daily via a breath-activated, multi-dose, dry-powder inhaler with placebo, in 43 adult patients (aged 15 to 78 years) with mild-to-moderate asthma (FEV1 71% of predicted normal) that was not controlled using bronchodilator therapy alone.. Efficacy was assessed by pulmonary function tests and asthma symptom control (as perceived by the patients) and the use of rescue medication.. Budesonide 400 microg (bid) was significantly more effective than placebo in improving morning peak expiratory flow (mean difference: 67.9 l/min; P < 0.005) and FEV1 (mean difference: 0.60 l; P < 0.005) over the 8-week treatment period. Onset of action, assessed by morning peak expiratory flow, occurred within the first two weeks of treatment.. Budesonide via a breath-activated, multi-dose, dry-powder inhaler results in a rapid onset of asthma control, which is maintained over time and is well tolerated in adults with mild-to-moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Asthma exacerbations are frequently linked to rhinovirus infections. However, the associated inflammatory pathways are poorly understood, and treatment of exacerbations is often unsatisfactory. In the present study we investigated whether antiinflammatory treatment with inhaled corticosteroids prevents any rhinovirus-induced worsening of lower airway inflammation. To that end, we selected 25 atopic patients with mild asthma who underwent experimental rhinovirus 16 (RV16) infection, while receiving double-blind, placebo-controlled treatment with the inhaled corticosteroid budesonide (800 microg twice a day) throughout the study period, starting 2 wk before infection. We assessed inflammatory cell numbers in the bronchial mucosa as obtained by bronchial biopsies 2 d before and 6 d after RV16 infection, and analyzed those in relation to cold symptoms, changes in blood leukocyte counts, airway obstruction, and airway hyperresponsiveness. RV16 colds induced an increase in CD3(+) cells in the lamina propria (p = 0.03) and tended to decrease the numbers of epithelial eosinophils (p = 0.06) in both groups analyzed as a whole. The T cell accumulation was positively associated with cold symptoms. Budesonide pretreatment improved airway hyperresponsiveness (p = 0.02) and eosinophilic airways inflammation (p = 0.04). Yet it did not significantly affect the RV16-associated changes in the numbers of any of the inflammatory cell types. We conclude that RV16 infection by itself induces only subtle worsening of airway inflammation in asthma, which is not improved (or worsened) by inhaled corticosteroids. The latter finding is in keeping with the limited protection of inhaled corticosteroids against acute asthma exacerbations.

Topics: Administration, Inhalation; Adult; Airway Resistance; Anti-Inflammatory Agents; Asthma; Biopsy; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Common Cold; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Rhinovirus; Severity of Illness Index; Treatment Outcome

To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids.. Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus and budesonide via Turbuhaler, 1000 microg twice daily for 7 days. Intravenous doses (200 microg) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chromatography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment.. The volume of distribution was found to be larger and the elimination half-life and mean absorption time longer for fluticasone than for budesonide. The systemic availability of budesonide via Turbuhaler (39%) was significantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5, 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1.3, 2.3]). In addition, at steady state the systemic availability of fluticasone via pMDI was significantly higher than via Diskus (ratio 1.6 [1.1, 2.2]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that for fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significantly between treatments with fluticasone Diskus and budesonide Turbuhaler (ratio 0.87 [0.65; 1.15]).. Budesonide and fluticasone differ in their pharmacokinetic properties in that although clearance is the same, the rate of uptake and elimination is slower for fluticasone. Despite a significantly higher pulmonary availability of budesonide via Turbuhaler, the plasma cortisol suppression is less than that of fluticasone via pMDI and similar to that of fluticasone via Diskus. There is no indication of any difference between healthy subjects and mild asthmatic patients in the pharmacokinetics and plasma cortisol suppression of fluticasone and budesonide.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Budesonide; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocortisone; Injections, Intravenous; Lung; Male; Middle Aged; Models, Biological; Peak Expiratory Flow Rate

Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed.. The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma).. We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated.. Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients.. Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma.

Topics: Administration, Intranasal; Adult; Allergens; Asthma; Blood Proteins; Bronchial Hyperreactivity; Budesonide; Conjunctivitis, Allergic; Double-Blind Method; Eosinophil Granule Proteins; Female; Humans; Immunotherapy; Male; Rhinitis; Ribonucleases

Ambient ozone concentration is related to asthma exacerbation, but few findings are available regarding the effects of pharmacologic asthma treatment on this relationship. The purpose of this study was to investigate whether inhaled corticosteroids inhibit ozone-induced airway neutrophilic inflammation, as detected in induced sputum, and reduce functional response to ozone exposure. Eleven subjects with mild persistent asthma were exposed for 2 h, on separate days, to 0.27 ppm ozone and to air in random order, before and after 4 wk of treatment with budesonide (400 microg twice daily). Before exposure, 1 and 2 h after the beginning of exposure, and 6 h after the end of exposure, pulmonary function was measured, and a total symptom score questionnaire was completed; 6 h after exposure, sputum was induced with hypertonic saline. Budesonide treatment did not inhibit the functional response to ozone exposure, as determined by reduction in FEV(1) and increase in total symptom score, but it significantly blunted the increase in the percentage of sputum neutrophils and interleukin-8 concentrations in the supernatant (p < 0.05). Therefore, 4 wk of inhaled budesonide blunted the airway neutrophilic inflammatory response but did not prevent the functional impairment of the airways after ozone exposure.

Topics: Administration, Inhalation; Adult; Air Pollutants; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Ozone; Respiratory Mechanics; Respiratory System; Single-Blind Method; Sputum; Vital Capacity

The aim of present study was to evaluate clinical, functional, and anti-inflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10-day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 microg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in I sec (FEV1) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV1 values (p < 0.05). These changes were more significant in group I than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Eosinophils; Female; Humans; Interleukin-5; Leukocyte Count; Male; Peak Expiratory Flow Rate; Theophylline; Time Factors

Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma.. To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma.. A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function.. In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level.. Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Male; Retrospective Studies; Treatment Outcome

There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists.. The purpose of the study was to evaluate whether regular treatment with formoterol affects the bronchodilator response to repeated puffs of albuterol, and also to assess the effects of acute administration of a bolus dose of IV or inhaled corticosteroid.. Twelve patients (mean [SD] age, 43 [15] years; FEV(1), 57 [17] % predicted) with stable, moderate to severe persistent asthma who were all taking inhaled corticosteroids were evaluated in a randomized, placebo-controlled, double-blind, double-dummy, crossover study. Patients received treatments each for 2 weeks followed by a bolus (IV/inhaled) of corticosteroid or placebo: (1) placebo inhaler bid + bolus placebo; (2) formoterol Turbuhaler 24 microg metered dosage bid (delivered dosage 18 microg bid) + placebo; (3) formoterol 24 microg bid + bolus IV hydrocortisone, 200 mg; or (4) formoterol 24 microg bid + bolus inhaled budesonide, 1,600 microg. Bronchodilator response to repeated puffs of albuterol (200 to 1,600 microg) for > 80 min was measured at 2 h after bolus administration of placebo or corticosteroid. The study was powered at the 80% level to detect a 20% difference in area under curve between 20 and 80 min (AUC) for FEV(1) response to albuterol as change from baseline (primary end point).. There was significant subsensitivity (p = 0.01) of the mean albuterol FEV(1) response (as AUC, L x s) after formoterol alone (737) as compared to placebo (1,453) along with partial reversal by steroid administration: formoterol + hydrocortisone (1, 050), and formoterol + budesonide (942). There was a similar pattern of subsensitivity (p = 0.03) for the mean albuterol forced expiratory flow between 25% and 75% of vital capacity response (as AUC, L): placebo (2,149), formoterol alone (1,002), formoterol + hydrocortisone (1,402), and formoterol + budesonide (1,271).. Regular treatment with formoterol produced significant bronchodilator subsensitivity to repeated puffs of albuterol, which was partially reversed by a bolus dose of systemic or inhaled corticosteroid.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchoconstriction; Budesonide; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Hydrocortisone; Male; Middle Aged; Respiratory Function Tests; Treatment Outcome

The aim of this open, randomized, crossover study was to compare the inhaled mass of budesonide suspension delivered by nebulization, using constant output, breath-synchronized, or pulsed jet nebulization techniques. The inhaled mass was defined as the amount of drug deposited on a filter between the inspiratory port of the nebulizer and the face mask or mouthpiece used by the subjects. The breath-synchronized nebulization delivered aerosol during the whole inspiration, whereas the pulsed nebulization was adjusted to deliver aerosol for up to 1 sec from the start of inspiration. Budesonide suspensions, 2 mL of 0.5 mg mL(-1), or 2 mL of 0.25 mg mL(-1), in single-dose respules, were used (AstraZeneca R&D Lund, Lund, Sweden). Eleven children (7 boys, age range 2.5-5.8 years) with either a clinical suspicion or a confirmed diagnosis of asthma and 11 healthy adolescents and adults (6 male, age range 13-52 years) were enrolled. With constant output nebulization, the median inhaled mass of budesonide was about 17.6% (range 9.6-21.2%) of the nominal dose (i. e., dose of drug in the respule per label claim) in adolescents and adults, and 18.1% in children (15.7-21.4%). With pulsed nebulization the median inhaled mass increased to 23.4% (22.0-28.1%) in children and to 32.8% (24.8-38.0%) in adolescents and adults (P < 0.001). With breath-synchronized nebulization median inhaled mass increased to 30.1% (21.7-28.1%) in children, but was unchanged (30.8%, 27.0-38. 0%) in adolescents and adults. The mode of nebulization (i.e., constant or breath-synchronized) had a statistically significant effect on the inhaled mass in children and adolescents or adults (P < 0.001). There was a statistically significant difference in inhaled mass between the breath-synchronized and pulsed nebulization in children only (P < 0.05). The results support the use of breath-synchronized but not pulsed nebulization with conventional nebulizers. The results of pulsed nebulization in children warrants further clinical studies.

Topics: Adolescent; Adult; Aerosols; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Respiration

This study was designed to compare the effects of a 6-month treatment with budesonide 100 microg bid (low dose) and 400 microg bid (standard reference dose) in controlling symptoms and lung function in a group of asthmatics with moderate asthma (baseline FEV(1) > or = 50% and < or = 90% of predicted values) previously treated with inhaled beclomethasone dipropionate (500 to 1,000 microg/d). Moreover, we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide.. After a 2-week run-in period and 1-month treatment with a high dose of budesonide (800 microg bid), 213 patients with moderate asthma were assigned to randomized treatments. Daily treatment included budesonide (bid) plus an additional treatment in case of exacerbation (qid for 7 days). Treatments were as follows: budesonide 400 microg plus placebo (group 1); budesonide 100 microg plus budesonide 200 microg (group 2); and budesonide 100 microg plus placebo (group 3). Symptoms and a peak expiratory flow (PEF) diary were recorded and lung function was measured each month. An exacerbation was defined as a decrease in PEF > 30% below baseline values on 2 consecutive days.. We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms. Moreover, symptoms were under control in all treatment groups throughout the study period. Similarly, lung function improved and remained stable, and no relevant differences between groups were observed. In each treatment group, the majority of patients had no exacerbations. In patients treated with the standard budesonide dose (group 1), the number of exacerbations and days with exacerbations were significantly lower than in group 3 (intention-to-treat analysis). Additionally, patients treated with low budesonide dose plus budesonide (group 2) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 (per-protocol analysis).. This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide, a low dose of budesonide (200 microg/d) is as effective as the standard dose (800 microg/d) in the control of symptoms and lung function over a period of several months. Furthermore, results showed that the addition of inhaled budesonide (800 microg/d) at onset of an asthmatic exacerbation has a beneficial clinical effect.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Long-Term Care; Lung Volume Measurements; Male; Middle Aged; Treatment Outcome

Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children.. Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations.. Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 0.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined.. In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1. 0 mg and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (-0.19, P =.003), and there was a small, statistically significant decrease in growth velocity (-0.8 cm/y, P =.002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C.. There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children.

Topics: Administration, Inhalation; Administration, Topical; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Body Height; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Glucocorticoids; Growth; Humans; Infant; Male; Suspensions

The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate. Seventy-five asthmatic children were randomly divided into three treatment groups: 30 to the fluticasone propionate (FP), 30 to the budesonide (BUD), and 15 to the cromone (CROM) group. FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter. The respective BUD doses were 800 and 400 microg/day. A low dose ACTH (0.5 microg/1.73 m2) test was performed before treatment and 2, 4, and 6 months later. The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean (<330 nmol/L). The low dose ACTH test was abnormal after both the high and low steroid doses in 23% of the children. At the 4 month measurement there were more abnormal tests in the BUD (n = 9) than in the FP (n = 5) group (P < 0.05). At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group (P < 0.01), whereas the difference between the FP and CROM groups was not significant. During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD, 0.03 in the children treated with FP, and 0.09 in the children treated with CROM; the difference between the BUD and FP groups was significant (P < 0.05). In conclusion, the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids. A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Dose-Response Relationship, Drug; Female; Fluticasone; Growth; Humans; Hydrocortisone; Male; Nedocromil

Adding inhaled long-acting beta(2)-agonists to a low dose of inhaled corticosteroids (ICS), results in better clinical asthma control than increasing the dose of ICS. However, this approach may mask underlying airway inflammation. In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum. After a 4-wk run-in period of treatment with budesonide (800 microg, twice daily), 60 patients with moderate asthma were randomly assigned to a 1-yr treatment with 400 microg of budesonide plus placebo, twice daily (BUD800), or 100 microg of budesonide plus 12 microg of formoterol, twice daily (BUD200+F). All drugs were administered via Turbuhaler. Budesonide (800 microg, twice daily) during run-in significantly reduced median sputum eosinophils from 4.5 to 0.68%. No significant changes in the proportion of eosinophils, EG2(+) cells, other inflammatory cells, or ECP levels in sputum were observed over the ensuing 1-yr treatment with BUD200+F or BUD800. Clinical asthma control was not significantly different between both groups. In conclusion, no significant differences in sputum markers of airway inflammation were observed during a 1-yr treatment with a low dose of inhaled budesonide plus formoterol compared with a higher dose of budesonide.

Topics: Adrenergic beta-Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Long-Term Care; Male; Middle Aged; Treatment Outcome

There is a limited body of evidence comparing the clinical effects of different inhaled corticosteroids in the treatment of asthma. This study compared the safety and efficacy of inhaled flunisolide and budesonide, both with unique delivery systems that may affect clinical response.. This multicenter study was carried out to compare the efficacy and safety of flunisolide, administered via AeroChamber, with budesonide, administered via Turbuhaler, in the treatment of moderate asthma.. Patients with moderate asthma, defined as an FEV1 of 40% to 85% of predicted, underwent a 2-week run-in period during which beclomethasone, 750 microg twice daily by MDI, was administered, along with salbutamol prn. Patients (n = 176) were then randomized into two groups. One group received flunisolide administered via AeroChamber, 750 microg (3 puffs), twice daily. The second group received budesonide administered via Turbuhaler, 600 microg (3 puffs), twice daily. All patients took salbutamol prn.. At the end of the 6-week treatment period, there were no significant differences (P > .05 for all comparisons) in efficacy between the groups as evaluated by any efficacy parameter. The treatment groups also did not differ significantly in the number of adverse events or in the incidence of oropharyngeal Candida infection.. Flunisolide administered by AeroChamber and budesonide administered via Turbuhaler demonstrate similar efficacy and safety in the treatment of moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Drug Tolerance; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Therapeutic Equivalency

Previous studies have shown that the regular administration of short acting beta-agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proinflammatory mechanism. The aim was to explore possible adverse effects of high-dose beta-agonist therapy and to assess any adverse interaction with corticosteroids. We undertook a randomized, crossover study to investigate the effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 microg twice a day), combined treatment, and placebo in subjects with mild to moderate asthma. Major endpoints were PD(15) saline, PD(20) methacholine, and induced sputum differential cell counts. Thirty-four subjects were randomized and 28 completed the study. PD(15) saline decreased on terbutaline alone compared with placebo treatment and on combined treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% CI = 0.43, 0.97], respectively). PD(20) methacholine was not affected by the use of terbutaline either alone or in combination with budesonide. The percentage of eosinophils in induced sputum increased during terbutaline treatment alone compared with placebo (median 8.3% versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did not affect the percentage of eosinophils compared with budesonide treatment alone. These findings support the hypothesis that short-acting beta-agonists have a permissive effect on airway inflammation and that when used in high dose there may be an unfavorable interaction with inhaled corticosteroids.

Topics: Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cell Count; Cross-Over Studies; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Middle Aged; Peak Expiratory Flow Rate; Sodium Chloride; Sputum; Terbutaline

We sought answers to two questions: 1) how can mild, early asthma best be detected? 2) how should it be treated and the treatment effect monitored?. Eighty adult patients with early, mostly mild asthma and 30 control subjects were examined by lung-function and biochemical tests. Patients were randomly assigned to two treatment groups. One group was treated with an inhaled steroid (budesonide) for 6 weeks, and the other first with an inhaled beta2-agonist (terbutaline) for 6 weeks and then with an inhaled steroid for 2 weeks.. Treatment with budesonide was effective: symptom scores, PEF, blood eosinophils, and sputum ECP values all improved. Terbutaline was ineffective by these criteria. For the detection of early asthma and for the following treatment effects, sputum and serum ECP assays are useful supplements to lung-function tests.. Treatment of early, mild asthma with an inhaled steroid is effective and worthwhile. Detection of the disease remains a problem, as both lung-function and biochemical tests have low sensitivities.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Biomarkers; Blood Proteins; Bronchodilator Agents; Budesonide; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Humans; Male; Middle Aged; Respiratory Function Tests; Ribonucleases; Sputum; Terbutaline; Time Factors

Rhinovirus infections in airway epithelial cells in vitro have been shown to upregulate intercellular adhesion molecule-1 (ICAM-1) expression. Epithelial ICAM-1, in its dual role as the major rhinovirus receptor and as adhesion molecule for inflammatory cells may be involved in the pathogenesis of rhinovirus-induced exacerbations of asthma.. We aimed to investigate the effect of experimental rhinovirus 16 (RV16) infection on ICAM-1 expression in bronchial mucosal biopsies in asthma. In addition, the effect of 2 weeks pretreatment with inhaled budesonide (800 microg b.d.) on RV16-associated changes in ICAM-1 expression was studied.. The study had a parallel, placebo-controlled design in 25 steroid-naive nonsmoking atopic asthmatic subjects. After 2 weeks budesonide (BUD) or placebo (PLAC) pretreatment bronchoscopy was performed 2 days before (day -2) and 6 days after (day 6) RV16 inoculation (on days 0 and 1). Immunohistochemical staining for ICAM-1 was performed on snap-frozen bronchial biopsies. ICAM-1 staining intensity on the basal epithelial cells was scored semiquantitatively from 1 (weak) to 3 (intense). Similarly, epithelial intactness was noted (1 = basal cells only, 2 = basal and parabasal cells, 3 = intact epithelium).. ICAM-1 scores were not significantly different between the groups at day -2 (P > or = 0.08). Subsequent RV16 infection was associated with a trend towards an increase in ICAM-1 expression in the BUD-group (P = 0.07), whereas the increase was significant in the PLAC-group (P = 0.03). However, the increase was not significantly different between the groups (P = 0.74). Epithelial intactness score was not different between the groups before RV16 infection (P > or = 0.07), and no significant changes were observed in either group (P > or = 0.59). Moreover, ICAM-1 score did not correlate significantly with epithelium score in either group, at any time-point (P > or = 0.27).. We conclude that an RV16 common cold in atopic asthmatic subjects is associated with increased ICAM-1 expression in the bronchial epithelium, which is not related to epithelial intactness. Glucocorticoid treatment does not appear to prevent the RV16-associated increased ICAM-1 expression. This suggests that other treatment modalities are required to protect against the spreading of infection during rhinovirus-induced exacerbations in asthma.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Bronchoscopy; Budesonide; Common Cold; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Immunoenzyme Techniques; Intercellular Adhesion Molecule-1; Male; Respiratory Mucosa; Rhinovirus

Dysphonia is a known local adverse effect of inhaled corticosteroids. This symptom was investigated by laryngoscopy and assessment in a voice laboratory. The effects of changing the treatment of patients with dysphonia, reported whilst using the pMDI, to pMDI plus Nebuhaler or Tubuhaler was also assessed.. Seventy-two patients reporting dysphonia and taking inhaled steroids from a pMDI entered a 12-week, open, parallel group study. Fifty-one completed the study per protocol; 26 in the Nebuhaler group [21 female, mean age 57 years (22-77)] and 25 in the Turbuhaler group [18 female, mean age 58 years (21-81)]. A dysphonia diary card was completed weekly. Voice laboratory assessments and laryngoscopy were performed on entry and at 12 weeks.. There were no differences in voice laboratory data, laryngoscopic evidence of disordered glottic closure and diary data between the two groups at 12 weeks. At study entry laryngoscopic appearances were normal in almost half the patients. Vocal cord bowing was rarely seen. Glottic closure changed in nine patients during the study period, but there was no correlation with voice symptoms. The trend of symptomatic improvement of voice status in the Turbuhaler group did not correlate with voice laboratory assessments and laryngoscopic evidence of disordered glottic closure. After 4 weeks, 40% of patients using Turbuhaler and 8% in the Nebuhaler group scored their voice status as better (P < 0.02) but there was no significant difference between the two groups at 12 weeks (Turbuhaler 52%, Nebuhaler 23%, P=0.08).. This study does not support the view that dysphonia in asthmatics inhaling corticosteroids is usually caused by myopathic bowing of the vocal cord muscles.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Laryngoscopy; Male; Middle Aged; Nebulizers and Vaporizers; Vital Capacity; Voice Disorders; Voice Quality

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Treatment Outcome

A pilot study was performed to investigate a clinical algorithm using serum-eosinophil cationic protein level (S-ECP) as an objective parameter for tapering the anti-inflammatory treatment in chronic childhood asthma. We studied 21 outpatient asthmatic children (6 girls and 15 boys, mean age 9 yr, range 3-12 yr, all with initial S-ECP > or = 15 microg/l) over a period of 12 months at monthly intervals. At each visit a short history, clinical examination, blood sample for S-ECP and eosinophil count, lung function tests and drug compliance were assessed. According to the initial S-ECP, patients were allocated to two anti-inflammatory treatment groups: patients with S-ECP between 15 microg/l and 30 microg/l were treated with Budesonide 200 microg twice daily, while patients with S-ECP of 30 microg/l and above received Budesonide 400 microg twice daily. After this induction treatment the anti-inflammatory medication was tapered at monthly intervals according to actually measured S-ECP: patients with S-ECP < 15 microg/l received sodium cromoglycate (SCG) 10 mg twice daily per inhalation via spacer, patients with S-ECP > or = 15 microg/l and < 30 microg/l received Budesonide 200 microg twice daily via spacer, and patients with S-ECP > or = 30 microg/l received Budesonide 400 microg twice daily. Prior to inhalation of topical steroids or SCG all patients had to inhale 500 microg Terbutaline twice daily for optimal bronchodilatation. The use of medication was assessed by weighing the metered dose inhaler containers each month. Our results showed a decrease in symptoms (p = 0.0001) and in S-ECP (p= 0.02) and MEF50% predicted (p= 0.02) after the initial month of Budesonide treatment. During a total of 246 months of investigation there was no need for emergency room treatment or hospital admission, and no need for oral steroids. During the whole study period there was a tendency for inhaled steroids to be more effective than SCG in reduction of markers of airway inflammation, improvement of symptoms and lung function. Inadequate use of medication was related to an increase in S-ECP in all treatment groups. From this open pilot study it is concluded that a clinical algorithm including S-ECP for tapering the anti-inflammatory treatment may be helpful in childhood asthma. These first observations should be confirmed by a controlled long-term study.

Topics: Algorithms; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Blood Proteins; Budesonide; Child; Child, Preschool; Chronic Disease; Cromolyn Sodium; Eosinophil Granule Proteins; Female; Humans; Male; Pilot Projects; Respiratory Function Tests; Ribonucleases; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the clinical efficacy of low-dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler, on exercise-induced bronchoconstriction (EIB) in children with mild asthma. Fifty-seven steroid-naive children (7-16 years old; 41 boys, 16 girls) with EIB participated in this sub-population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s (FEV1) > or = 10% after a standardized treadmill test. Mean baseline FEV1 was 100.3% of predicted, and mean maximum fall in FEV1 after the standardized exercise test was 22%. The study was a double-blind, randomized, parallel-group design. After 2 weeks of run-in, the children received inhaled budesonide 100 microg or 200 microg once daily in the morning, 100 microg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV1 after the exercise test was significantly less in all three budesonide groups (7.2-7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p <0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.

Topics: Administration, Inhalation; Adolescent; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Humans; Respiratory Function Tests

The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Patient Compliance; Vital Capacity

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Despite a good understanding of the disease and its treatments, asthma continues to place a large economic burden on healthcare systems. As such, it is important to consider the economic impact of alternative therapeutic options for the treatment of this condition to ensure that scarce resources are used in the most efficient manner possible. Thus, the aim of asthma management from an economic perspective is to reduce the burden of this disease through maximizing health gain with available resources. A prospective economic analysis was conducted as part of a multicentre, randomized, double-blind, comparative trial of salmeterol/fluticasone propionate combination product (SFC) 50/250 microg twice daily vs. budesonide (800 microg twice daily) in adults and adolescents with asthma who were symptomatic despite treatment with inhaled corticosteroids at doses of 800-1200 microg day(-1). Treatment effectiveness was measured in terms of successfully-treated weeks, defined as a > or =5% improvement in morning peak expiratory flow, episode-free days (a day without the need for rescue medication, no nocturnal awakening or adverse events) and symptom-free days. Cost-effectiveness analyses were performed using direct healthcare and drug costs, from the perspective of the Swedish healthcare system (1998 prices), with appropriate sensitivity analyses to test the robustness of the findings. Overall, SFC produced significantly higher (P<0.001) proportions of successfully-treated weeks, episode-free days and symptom-free days. Direct asthma management costs were similar between the two groups [SEK19.6 ($US2.4) for SFC vs. SEK18.5 (SUS2.2) for budesonide]. The cost per successfully-treated week was lower for SFC than for budesonide [SEK204 ($US24.8) vs. SEK300 ($US36.4) per week], as were the costs per episode-free day [SEK51.1 ($US6.2) vs. SEK75.1 ($US9.1) per day] and symptom-free day [SEK42.2 ($US5.1) vs. SEK53.0 ($US6.4) per day]. Incremental cost-effectiveness ratios showed that the additional costs to achieve additional benefits with SFC were minimal. Costs per additional successfully-treated week, symptom-free day and episode-free day with SFC were SEK31.6 ($US3.9), SEK9.2 ($US1.1) and SEK7.7 ($US0.9), respectively, relative to budesonide. Sensitivity analysis showed that the results were stable over a wide range of assumptions. The results suggest that SFC is a more cost-effective treatment than budesonide in the management of moderate to severe asthma.

Topics: Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Treatment Outcome

A randomized, double-blind, placebo-controlled, parallel-group study including 481 children at 37 centers in the United States demonstrated the efficacy and safety of budesonide inhalation suspension in doses of 0.25 mg once daily, 0.25 mg twice daily, 0.5 mg twice daily, and 1.0 mg daily in infants and young children with persistent asthma. The retrospective analysis presented here compares the efficacy of treatment with the suspension administered through a face mask or mouthpiece. All patients receiving budesonide inhalation suspension via face mask or mouthpiece showed clinical improvements in nighttime and daytime asthma symptoms as compared with administration of a placebo. The improvements were of similar magnitude as those observed in an analysis of all patients treated. Improvements in nighttime asthma symptoms were statistically significant with budesonide at 0.25 mg daily (p = 0.040), 0.25 mg twice daily (p = 0.008), and 0.5 mg twice daily (p = 0.046) delivered by face mask. In patients using mouthpieces, nighttime asthma symptoms improved significantly in the 0.25-mg twice-daily (p = 0.005) and 1.0-mg daily (p = 0.035) groups. Patients receiving budesonide at 0.5 mg twice daily via a face mask improved significantly in daytime asthma symptoms (p = 0.009). The use of breakthrough medication was reduced in patients receiving budesonide via face masks or mouthpieces relative to placebo, and treatment was well tolerated in all study groups. This retrospective analysis suggests that nebulized budesonide inhalation suspension can be administered effectively by either face mask or mouthpiece to young children with persistent asthma.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Infant; Male; Masks; Nebulizers and Vaporizers; Retrospective Studies; Suspensions; Treatment Outcome

This study is an extended follow-up for 24 months of a 12-week trial to study the long-term clinical efficacy of low-dose inhaled budesonide (BUD) once or twice daily in children with mild asthma. A total of 122 children (mean age 9.7 years, girls/boys; 42/80) with mild asthma (FEV1 103.7% of predicted, reversibility in FEV1 3.5%, and fall in FEV1 after exercise 12.2%), not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. The children were treated with inhaled BUD 100 or 200 microg administered via Turbuhaler once daily in the morning, 100 microg twice daily, or placebo for 27 months. Exercise and methacholine challenges were performed at 3-month intervals the first year and at 6-month intervals the second year, in a total of seven visits. A significant dose-response effect favoring BUD 200 microg daily (vs 100 microg daily) was found when comparing changes in FEV1, FEF25%, and FEV50%; the fall in FEV1 after an exercise test; and the effect on blood eosinophils. Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 microg daily compared to placebo. Growth rate was not significantly affected except in children aged 7-11 years at baseline after 12 months of treatment. In conclusion, 100 or 200 microg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise-induced asthma and achieving nearly normal lung function. Baseline lung function was not significantly affected in this group of children with mild asthma.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Eosinophil Granule Proteins; Eosinophils; Exercise Test; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Patient Compliance; Placebos; Pulmonary Eosinophilia; Ribonucleases

There is uncertainty about the development of airway tolerance to beta-agonists and the phenomenon of rebound bronchoconstriction on beta-agonist withdrawal. We have recently completed a study of the regular terbutaline and budesonide treatment in asthma. We report our observations on the effect of starting and stopping terbutaline treatment on morning and evening peak flows. The study was a randomized four-way, double-dummy, cross-over comparison of regular inhaled terbutaline (500-1000 microg four times daily), budesonide, combined treatment and matching placebo. Each treatment was given for 6 weeks following a 4 week single-blind placebo washout. Ipratropium was used for symptom relief. No other asthma medication was permitted during either the treatment or wash-out periods. Evaluable data were obtained from 52 subjects for both placebo and terbutaline treatment. Changes in mean morning and evening peak flows during terbutaline treatment were compared to the baseline peak flows during the last 2 weeks of the preceding washout. The peak flow changes on stopping terbutaline were also analysed. Mean morning peak flow was not significantly different during terbutaline treatment when compared to either baseline or placebo treatment. Evening peak flows were significantly higher during terbutaline treatment [mean increase 23.1 l min(-1) (95% CI = 18.8, 27.4)]. Analysis of the peak flow changes on a day-by-day basis revealed an initial increase in morning peak flows for the first 2 days of treatment of 19.2 and 13.41 min(-1) [increases of 25.0 and 17.31 min(-1) in comparison with the corresponding values during placebo (P<0.01)] followed by a return to baseline. The increase in evening peak flows was also greater for the first 2 days of treatment than for the remainder of the treatment period (P<0.01). On ceasing terbutaline treatment there was a fall in mean morning peak flow below the baseline on the following morning of 21.6 l min(-1) (P<0.05 compared to placebo). The temporary increase in morning peak flows and greater than expected rise in evening peak flows for the first 2 days of treatment suggest the development of tolerance to the bronchodilator effect of terbutaline. Similarly, the fall in morning peak flows on treatment withdrawal suggests rebound bronchoconstriction. These effects are likely to be mediated by downregulation of the beta-receptor during treatment. The clinical significance of these changes is uncertain in view of the stability of ove

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Substance Withdrawal Syndrome; Terbutaline; Vital Capacity

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines. The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks (double-blind), then 1,600 microg x day(-1) for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1-16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose. By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200- and 1,600-microg x day(-1) starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L x min(-1), p=0.8). Subjects starting with 3,200 microg x day(-1) were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of > or = 3.92 micromol by week 16 (p=0.03) [corrected]. During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 microg x day(-1), p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days x week(-1), beta2-agonist use 0.2 occasions x day(-1), and PD20 2.4 micromol). In subjects with poorly controlled asthma, a starting dose of 1,600 microg x day(-1) budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Single-Blind Method; Treatment Outcome

Repeated low-dose allergen challenge increases airway hyperresponsiveness and sputum eosinophils in atopic asthmatics. Inhaled corticosteroids attenuate the airway responses to high-dose allergen challenge, but have not been evaluated against repeated low dose challenge.. This study evaluates the effects of once daily treatments of two doses of inhaled budesonide on airway responses to repeated low-dose allergen challenge.. Eight atopic asthmatics with a dual airway responses to inhaled allergen were recruited into a randomized, double-blind crossover, placebo-controlled study. In the mornings of four consecutive days (day 1-day 4), subjects inhaled budesonide 100 microg, 400 microg, or placebo, 30 min before inhaling a concentration of allergen causing a 5% early fall in FEV1. Airway hyperresponsiveness to methacholine and sputum eosinophils were measured at baseline, on the afternoon of day 2, day 4, and 24 h after the last challenge. There was a 1-week washout between each of the three treatment periods.. The repeated low-dose allergen challenge induced increases in the percentage sputum eosinophils from 2.0 +/- 0.7% at baseline to 16.6 +/- 7.1% on day 4 (P = 0.002), and this effect was reduced by once daily budesonide 100 microg to 5.6 +/- 1.8% (P = 0. 01) and by once daily budesonide 400 microg to 3.1 +/- 0.9% (P = 0. 004). Also, the allergen-induced methacholine airway hyperresponsiveness which occurred by day 4 (P = 0.03) of the repeated low dose challenge was inhibited by budesonide 400 microg (P = 0.017).. Both budesonide 100 microg and 400 microg inhaled once daily significantly reduces allergen-induced sputum eosinophilia after repeated low dose challenge; however, only the higher dose also attenuates the allergen-induced airway hyperresponsiveness.

Topics: Adult; Allergens; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Respiratory System

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper-reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 microg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 microg twice per day for two months. Follow-up consisted of out-patient check-ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bronchiolitis; Bronchodilator Agents; Budesonide; Disease Management; Female; Humans; Infant; Infant, Newborn; Male; Outcome Assessment, Health Care; Respiratory Syncytial Virus Infections

The choice of patient-device interface (face mask or mouthpiece) influences the inhaled mass and the lung deposition of nebulized drugs. The use of a mouthpiece has been shown to double the lung deposition compared with use of a face mask. We have determined the inhaled mass of budesonide using a jet nebulizer with mouthpiece in either a constant output or breath-synchronized mode in children. We have also determined the inhaled mass when the jet nebulizer is used with a nonsealing face mask in a constant output mode. The study was a 1-day, randomized, crossover, single-center study involving 158 asthmatic children (age range 5.1-15.7 years). Nebulized budesonide was administered in three single nominal doses of 1.0 mg by means of a jet nebulizer. The inhaled mass of budesonide was defined as the amount of drug deposited on filters positioned between the nebulizer and the mouthpiece or face mask. The mean inhaled mass of budesonide from different age groups ranged from 1 7.1% to 21.6% of the nominal dose with breath-synchronized nebulization with a mouthpiece. With constant output nebulization with a mouthpiece, the mean inhaled mass ranged from 8.9% to 12.2%, and with a nonsealed face mask the mean inhaled mass ranged from 5.0% to 6.9%. For children using jet nebulizers with mouthpiece, breath-synchronized nebulization appears to be superior to conventional constant output nebulization. The use of jet nebulizers with nonsealing face masks should be avoided.

Topics: Administration, Inhalation; Adolescent; Aerosols; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Humans; Masks

To define the mechanisms by which inhaled glucocorticosteroid regulates allergen-induced airway inflammation, a double-blind, placebo-controlled, cross-over study with inhaled budesonide was conducted in 14 subjects with allergic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were randomized to budesonide (400 microgram, twice daily) or placebo treatment for 4 wk. At the end of each treatment phase, whole-lung allergen inhalation challenge was performed, followed by BAL 48 h later. Budesonide treatment improved the FEV(1), attenuated both the immediate- and late-phase response to allergen, and prevented the increase in bronchial hyperresponsiveness after allergen challenge. Budesonide treatment also decreased allergen-induced airway eosinophilia. To determine the effects of budesonide on airway cell function, BAL cells were stimulated ex vivo with the T cell mitogen PHA, and cytokine generation was measured by ELISA. Budesonide decreased ex vivo generation of IL-5 and IFN-gamma by BAL cells. Ex vivo IL-5 production was significantly correlated with the number of airway eosinophils (r(s) = 0.61), and levels of eosinophil-derived neurotoxin (EDN) (r(s) = 0.57) and IL-5 (r(s) = 0.52) in BAL fluid. Moreover, PHA-induced IL-5 generation correlated with FEV(1) fall during the late-phase response to allergen (r(s) = 0.60). Budesonide decreased circulating eosinophils and serum levels of IL-5, but did not reduce IL-5 generation by peripheral blood mononuclear cells. The reduction in circulating eosinophils correlated with the decrease in levels of EDN (r(s) = 0.61) in BAL fluid and late response to inhaled allergen (r(s) = 0.51). These findings suggest that long-term treatment with inhaled budesonide reduces airway cell generation of cytokines, specifically IL-5, which then decreases circulating eosinophils and their availability for recruitment to the airway after allergen exposure.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Male; Respiratory Hypersensitivity; Systemic Inflammatory Response Syndrome

To measure drug adherence in children with mild asthma receiving long term prophylactic treatment.. Double blind randomised placebo controlled trial. Patients received inhaled budesonide 100 microg or 200 microg daily, or placebo for 27 months. All participants were asked to inhale medication or placebo from two different Turbuhalers (morning and evening) during the study. A total of 122 children (80 boys, 42 girls) aged 7-16 years with mild asthma (mean FEV(1) 103.7% of predicted) were included in the trial. Drug adherence was assessed by counting the number of remaining doses in the inhaler when study medication was returned at six month intervals.. A statistically significant and continuing decrease in measured drug adherence was found from three to nine months and then to 27 months, reaching mean values of 40.6% and 46. 9% for inhaled morning and evening medication respectively. Drug adherence declined more rapidly in the placebo group (compared to active treatment); this difference became significant after two years of treatment. Children aged 9 years or less had better drug adherence during the entire study period, but the difference was only significant for the first three months of the study. Measured drug adherence was significantly higher for evening medication compared to morning medication for all study intervals after nine months.. Measured drug adherence diminishes significantly when treating children with mild asthma in a long term trial. This emphasises the importance of monitoring compliance in clinical trials.

Topics: Adolescent; Age Factors; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Patient Compliance

To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler).. A randomised double blind, placebo controlled crossover study with two six-week periods.. Outpatient clinic in secondary referral centre.. A total of 27 prepubertal children aged 6-13 years.. Formoterol 12 microg and dry powder budesonide 100 microg twice daily in one period; placebo and dry powder budesonide 200 microg twice daily in the other.. Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control.. During budesonide 200 microg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods.. In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.

Topics: Adolescent; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Collagen; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Growth; Humans; Leg; Male

The Taifun dry powder inhaler (Leiras OY, Turku, Finland) is a breath-actuated, multidose device, each metered dose containing 200 micrograms of budesonide. A two-way randomized crossover gamma scintigraphic study was performed in 10 asthmatic patients to determine the in vivo deposition pattern of budesonide inhaled from the Taifun. In vitro radiolabelling validation studies demonstrated that the radiolabel could be used as an accurate marker to assess in vivo drug deposition. Patients used either maximal inspiratory effort (targeted peak inhalation flow 30 L/min) or submaximal inspiratory effort (targeted peak inhalation flow 15 L/min) on each study day. Mean (S.D.) whole lung deposition (% of metered dose) was 34.3 (5.8)% and 29.6 (5.9)% for the two inhalation flows. The intersubject coefficient of variation in lung deposition was less than 20% on both study days. Drug was deposited uniformly across the central, intermediate, and peripheral lung regions for maximal and submaximal inspiratory efforts. The study suggests that the Taifun is a superior drug delivery device compared with many other inhalers, in terms of the amount of drug deposited in the lungs, the reproducibility of the lung dose, and the relative flow--independence of lung deposition.

Topics: Adult; Aerosols; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Female; Gamma Cameras; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Radionuclide Imaging; Respiratory Function Tests; Statistics, Nonparametric; Technetium Compounds; Thorax

Inhaled corticosteroids have beneficial effects on pulmonary function and inflammation in patients with asthma, but they also cause systemic adverse effects, such as adrenal suppression. We evaluated the therapeutic index of inhaled corticosteroids in asthmatic patients by comparing their dose-response effects on lung function, surrogate markers of airway inflammation, and tests of adrenal function.. After a 10-day placebo run-in, we evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients, aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements were made of bronchial reactivity, exhaled nitric oxide (a marker of airway inflammation), spirometry, serum eosinophilic cationic protein concentration, and 10-hour overnight urinary cortisol excretion. Plasma cortisol levels were measured at 8 AM and after stimulation with human corticotropin releasing factor.. For measurements of pulmonary function and exhaled nitric oxide, there was a plateau in the mean response to budesonide between 400 microg (low dose) and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg (high dose) per day. Effects on plasma cortisol levels showed maximal suppression at 1,600 microg of budesonide per day. The proportion of patients with an optimal therapeutic index, in terms of a good airway response (fourfold decrease in bronchial hyperreactivity) and minimal systemic response (overnight urinary cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose (52%) budesonide. The proportion of patients with a suboptimal therapeutic index, a good airway response with a marked systemic response (overnight urinary cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high dose.. In patients with mild-to-moderate atopic asthma, there were dose-related effects of budesonide on surrogate markers of inflammation (bronchial hyperreactivity and serum eosinophilic cationic protein), although higher doses were associated with adrenal suppression and a decrease in the therapeutic index.

Topics: Administration, Inhalation; Adult; Asthma; Breath Tests; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Nitric Oxide; Respiratory Function Tests; Spirometry

The aim of this study was to evaluate the oral steroid-sparing capacity of budesonide Turbuhaler.. One hundred and thirteen oral steroid-dependent patients were treated for 6 months with placebo or budesonide 800 microg or 1600 microg daily. Every second week the oral steroid dose was reduced if asthma control permitted.. The reductions in oral steroid doses were 9, 35 and 60% in the placebo and budesonide 800 microg and 1600 microg groups, respectively. Oral steroid treatment could be discontinued in 4% (placebo), 15% (800 microg) and 23% (1600 microg). Mean peak expiratory flow values increased by 21 and 24 L/min in the budesonide groups but decreased by 6 L/min in the placebo group. Asthma attack, activity and sleep scores remained unchanged showing maintained efficacy. Plasma cortisol levels increased and an adrenocorticotropic hormone test showed improved adrenocortical response in both budesonide groups, indicating improved safety. Adverse drug reactions were infrequent and mild in all study groups.. Budesonide Turbuhaler, 800 microg and 1600 microg daily, resulted in a significant reduction in oral steroid usage in steroid-dependent patients. The effect was achieved with maintained asthma control together with improvements in lung and adrenal functions.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hydrocortisone; Japan; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Prednisolone; Prospective Studies; Sleep

The aim of this study was to investigate the dose-response for inhaled budesonide via Turbuhaler in Japanese patients with mild to moderate asthma.. Inhaled budesonide 100 microg, 200 microg, 400 microg or placebo was administered twice daily via Turbuhaler for 6 weeks, to 267 adult Japanese patients (mean age 51 years) with mild-to-moderate, non-steroid-dependent bronchial asthma, in a double-blind, placebo-controlled, randomized, parallel group study. The patients had to be symptomatic for more than 3 days/week and have an average morning peak expiratory flow (PEF) 50-80% of predicted normal value.. The response to budesonide was rapid, all treatments showing a significant improvement in morning PEF after 1 week (P<0.05). During week 6, mean improvements of 15, 45, 53 and 71 L/min were observed for the placebo, 200 microg, 400 microg and 800 microg budesonide groups, respectively. Compared with placebo all improvements in the budesonide groups were statistically significant and a significant dose-response was demonstrated (P<0.001). The difference between the 200 microg and 800 microg doses was significant. Also, for several secondary efficacy variables (e.g. evening PEF, symptom score, treatment score, daily activity score and sleep score) significant dose-responses were shown. Other variables included the investigators' assessments of improvement and usefulness. They also showed statistically significant dose-response relationships and confirmed the rapid onset of action. Budesonide was well tolerated at all tested doses, with a low incidence of adverse events, all of which were minor in severity.. Budesonide Turbuhaler in the doses 100 microg to 400 microg twice daily was effective, well tolerated and showed a rapid onset of action in patients with mild-to-moderate asthma. Dose-response was demonstrated for several variables of clinical efficacy.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Circadian Rhythm; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Prospective Studies; Treatment Outcome; Vital Capacity

Short-term studies have shown that inhaled corticosteroids may reduce the growth of children with asthma. However, the effect of long-term treatment on adult height is uncertain.. We conducted a prospective study in children with asthma to examine the effect of long-term treatment with inhaled budesonide on adult height. We report on 211 children who have attained adult height: 142 budesonide-treated children with asthma, 18 control patients with asthma who have never received inhaled corticosteroids, and 51 healthy siblings of patients in the budesonide group, who also served as controls.. The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment (range, 3 to 13) at a mean daily dose of 412 microg (range, 110 to 877). The mean cumulative dose of budesonide was 1.35 g (range, 0.41 to 3.99). The mean differences between the measured and target adult heights were +0.3 cm (95 percent confidence interval, -0.6 to + 1.2) for the budesonide-treated children, -0.2 cm (95 percent confidence interval, -2.4 to +2.1) for the control children with asthma, and +0.9 cm (95 percent confidence interval, -0.4 to +2.2) for the healthy siblings. The adult height depended significantly (P<0.001) on the child's height before budesonide treatment. Although growth rates were significantly reduced during the first years of budesonide treatment, these changes in growth rate were not significantly associated with adult height.. Children with asthma who have received long-term treatment with budesonide attain normal adult height.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Body Height; Budesonide; Child; Child, Preschool; Female; Glucocorticoids; Growth; Humans; Male; Prospective Studies

Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use.. We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms.. There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups.. In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Growth; Hospitalization; Humans; Lung; Male; Nedocromil; Prednisone; Vital Capacity

To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of (1) 400 microgram orally inhaled budesonide plus 200 microgram intranasal budesonide (BUD) or (2) 10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p < 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean AMP PC(20) (mg/ml), there was an improvement (p < 0.05), compared with PL (47), for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Budesonide; Cetirizine; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Inflammation Mediators; Leukotriene Antagonists; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides

We hypothesized that measurement of lung function (LF) and bronchial hyperresponsiveness (BHR) could serve as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids in asthmatic children aged 2 to 5 yr. We studied 38 children (mean age: 53 mo; range: 35 to 71 mo) with moderately severe asthma in a single-center, randomized, double-blind, parallel-group, placebo-controlled study involving 8 wk of treatment. Budesonide (BUD) 400 microgram twice daily was administered via a pressurized metered-dose inhaler and metal spacer device. Symptom scores (SSc) and use of short-acting beta(2)-agonist were monitored with diary cards. LF in awake children was measured as the specific airway resistance (sRaw), using whole-body plethysmography; as resistance by the interrupter technique (Rint); and as resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. Cold air challenge (CACh) and methacholine challenge (MCh) were used to assess BHR. Children in the BUD group experienced significantly fewer night- and daytime symptoms (p < 0.05) and more symptom-free days (p < 0.05), but not nights (p = 0.07), than children in the placebo group. Daytime (p < 0.05) but not nighttime (p = 0.09) use of rescue medication and asthma exacerbation rates (3.7 versus 9.3 exacerbations/yr) (p = 0.006) were both in favor of BUD. LF measured with the Rint technique, Rrs5, and Xrs5 were significantly improved by BUD. BHR as measured by CACh improved significantly with BUD, whereas no improvement was found on MCh. In conclusion, inhaled BUD at a total dose of 800 microgram daily significantly improved SSc, asthma exacerbation rates, lung function, and BHR as assessed by CACh in asthmatic children aged 2 to 5 yr.

Topics: Administration, Inhalation; Airway Resistance; Asthma; Bronchial Provocation Tests; Budesonide; Child, Preschool; Cold Temperature; Double-Blind Method; Female; Humans; Male; Methacholine Chloride

Prolonged treatment with inhaled steroids is recommended for long-term control of asthma in children; however, it can interfere with growth and body composition.. The aim of this study is to answer the question whether 6 months treatment with inhaled steroids causes body fat accumulation and growth velocity reduction.. Hospital-based, open study of body composition [by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and skinfolds] and growth of 26 asthmatic children, treated for 6 months with inhaled steroids [budesonide (BUD) 400 microg/day (group 1) or fluticasone proprionate (FP) 200 microg/day (group 2)], sodium cromoglycate and beta2-agonist (salbutamol) compared with a control group of 16 asthmatic children treated only with sodium cromoglycate and beta2-agonist.. On average, total and regional fat mass, adjusted for pubertal stage and gender, and growth velocity were similar in all three groups of patients and were not influenced by treatment (% mean change +/- 1 SD of fat mass during treatment in BUD 0.1 +/- 3.0%, FP -1.1 +/- 3%, and control -2.8 +/- 3.5%; ANOVA P > or = .05); however seven patients, two in group 1 (1 preschool child), three in group 2 (2 preschool children) and two in the control group (two prepubertal boys aged 8.5 and 9.5 year), during treatment, showed a growth velocity standard deviation score below the third percentile.. A 6-month treatment with inhaled BUD and FP does not induce body fat accumulation; however, in a few preschool children the treatment was associated with growth velocity below the third percentile. Our results suggest the need for constant monitoring of growth in all asthmatic children on chronic treatment with inhaled steroids. Further studies devoted to the effects of inhaled steroids use in preschool children are needed.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Androstadienes; Anthropometry; Anti-Inflammatory Agents; Asthma; Body Composition; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Female; Fluticasone; Glucocorticoids; Growth; Humans; Male; Skinfold Thickness

We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers.. Fifteen patients with atopic persistent asthma were evaluated (mean age, 32.4 years; FEV(1), 75.2% predicted) in a randomized, double-blind, double-dummy, placebo-controlled crossover study with a 1-week placebo washout period, comparing the following once-daily nighttime treatments: (1) formoterol (FM), 12 microg, for 2 weeks and FM, 24 microg, for 2 weeks; or (2) budesonide (BUD), 400 microg, for 2 weeks and BUD, 800 microg, for 2 weeks; or (3) FM, 12 microg, plus BUD, 400 microg, for 2 weeks and FM, 24 microg, plus BUD, 800 microg, for 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitric oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment.. The results of AMP challenge (provocative concentration causing a 20% fall in FEV(1)) at 4 weeks showed significant (p<0.05) improvements after patients had received all active treatments compared to placebo (20 mg/mL), with FM plus BUD, 261 mg/mL, being superior (p<0.05) to FM alone, 82 mg/mL, but not to BUD, 201 mg/mL. NO and ECP showed significant (p<0.05) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone. Combination therapy was associated with optimal patient preference (rank order, FM plus BUD > FM > BUD; p<0.0005), highest domiciliary peak expiratory flow, and lowest rescue inhaler usage. All three treatments produced equivalent improvements in spirometry.. Patients preferred once-daily combination therapy, but this had no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting beta(2)-agonist.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adult; Asthma; Biomarkers; Blood Proteins; Breath Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Eosinophil Granule Proteins; Eosinophils; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Prognosis; Ribonucleases; Spirometry

(1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study.. A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months.. Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice.. Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness.. Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed.. (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues.. Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups.. Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Topics: Adolescent; Androstadienes; Anthropometry; Anti-Asthmatic Agents; Asthma; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cost-Benefit Analysis; Female; Fluticasone; Health Care Costs; Humans; Infant; Longitudinal Studies; Male; Pilot Projects; Quality of Life; Regression Analysis; Respiratory Function Tests; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; United Kingdom

To evaluate the influence of early antiinflammatory therapy in the development of asthma 3 years after hospitalization for wheezing in infancy. In addition, the effects of allergic sensitization and respiratory syncytial virus (RSV) infection on the development of asthma were investigated.. A randomized, controlled follow-up study in a university hospital that provides primary hospital care for all pediatric patients in a defined area.. Eighty-nine infants under 2 years of age who had been hospitalized for infection associated with wheezing and followed up for 3 years.. Early antiinflammatory therapy was given for 16 weeks; 29 patients received cromolyn sodium and 31 received budesonide. Twenty-nine control patients received no therapy.. Clinical diagnosis of current asthma, defined as having at least 3 episodes of physician-diagnosed wheezing and either a wheezing episode during the preceding year or ongoing antiinflammatory medication for asthma.. Fourteen (48%) patients in the former cromolyn group, 15 (48%) in the former budesonide group, and 16 (55%) in the control group had current asthma. The significant predictors of asthma were age over 12 months (risk ratio [RR] 4.1; 95% confidence interval [CI] = 1.59-10.35), history of wheezing (RR 6.8; CI = 1.35-34.43), and atopic dermatitis on study entry (RR 3.4; CI = 1.17-9.39). Skin prick test positivity at the age of 16 months significantly predicted asthma (RR 9.5; CI = 2.45-36.72). In addition, all of the 18 (20%) children sensitized with furred pet developed asthma. RSV identification (RR 0.3; CI = 0.08-0.80) and early furred pet contact at home (RR 0.3; CI 0.10-0.79) were associated with the decreased occurrence of asthma.. Antiinflammatory therapy for 4 months has no influence on the occurrence of asthma 3 years after wheezing in infancy. Early sensitization to indoor allergens, especially to pets, and atopic dermatitis predict subsequent development of asthma. RSV infection in wheezing infants may have a better outcome than other infections.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Comorbidity; Cromolyn Sodium; Dermatitis, Atopic; Disease Progression; Female; Finland; Follow-Up Studies; Food Hypersensitivity; Hospitalization; Humans; Infant; Male; Prospective Studies; Respiratory Hypersensitivity; Respiratory Sounds; Respiratory Syncytial Virus Infections; Risk Factors

The extent to which inhaled glucocorticoids increase the risk of intraocular pressure elevation has been controversial.. The authors attempt to assess such risk attributable to budesonide, an inhaled glucocorticoid for asthma therapy.. Data were pooled from four prospective, randomized, double-blind, parallel-group, placebo-controlled, multicenter clinical trials of 12 to 20 weeks in duration. One thousand two hundred and fifty-five patients, 6 to 70 years of age whose intraocular pressures (IOPs) were less than 23 mmHg at screening were randomized to receive placebo or inhaled budesonide at doses ranging from 100 to 800 microg, administered twice daily. Intraocular pressure was measured at screening and at the end of double-blind treatment. Intraocular change was compared between budesonide and placebo, accounting for the confounding effects of gender, race, age, history of diabetes, history of hypertension, clinical trial, systemic glucocorticoid use during the trials, ophthalmic glucocorticoid use during the trials, and prior oral glucocorticoid use.. No budesonide treatment effect on the IOP was evident either in the crude analysis or after adjustment for possible confounding factors. For patients exposed to budesonide at a total daily dose of 1600 microg for 20 weeks, there was no difference in IOP change compared with the placebo controls.. No association with an increased IOP was observed in asthmatic patients treated with budesonide at daily doses ranging from 200 to 1600 microg for durations of 12 to 20 weeks. The subgroup analysis, which focused on the highest dose and longer term therapy was reassuring, as was the overall result.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Humans; Intraocular Pressure; Male; Middle Aged

Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.

Topics: Administration, Inhalation; Adrenal Cortex; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Time Factors

Allergen inhalation by dual responder subjects with atopic asthma is associated with an increase in circulating eosinophil/basophil colony-forming units (Eo/B CFU) and granulocyte-macrophage colony- stimulating factor (GM-CSF) immunolocalization in Eo/B colony cells grown in vitro. The current study examined the effect of the inhaled corticosteroid, budesonide, on the number of allergen- induced circulating eosinophils and Eo/B CFU, and immunolocalization of GM-CSF and interleukin-5 (IL-5) in Eo/B colony cells grown in vitro. Sixteen subjects with mild atopic asthma were treated for either 7 or 8 d with 200 microg inhaled budesonide or placebo twice a day. Peripheral blood was collected before and 24 h after allergen inhalation challenge and nonadherent mononuclear cells (NAMC) were grown in methylcellulose culture. Eo/B CFU were enumerated after 14 d in culture, and prepared on slides for immunocytochemistry. Budesonide attenuated the allergen-induced increase in circulating eosinophils (4.0 +/- 0.4 x 10(5)/ml versus 6.5 +/- 0.7 x 10(5)/ml, p = 0.0001), circulating Eo/B CFU (12.4 +/- 2.3/10(6) NAMC versus 18.8 +/- 4.6/10(6) NAMC, p = 0.05), and immunolocalization of GM-CSF in Eo/B colony cells (11.8 +/- 1.9% positive versus 18.0 +/- 2.2%, p = 0.01) but not immunolocalization of IL-5 (7.9 +/- 1.4% versus 4.5 +/- 0.6%, p > 0.05). Inhaled budesonide attenuated the number of allergen-induced circulating eosinophils and their progenitors grown in the presence of GM-CSF, which may partially be a result of regulating eosinophil progenitor expression of the autocrine growth factor GM-CSF.

Topics: Administration, Inhalation; Allergens; Analysis of Variance; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Colony-Forming Units Assay; Cross-Over Studies; Cytokines; Double-Blind Method; Eosinophils; Humans; Stem Cells; Time Factors

Mometasone furoate (MF) administered by dry powder inhaler (DPI) was composed with budesonide (BUD) Turbuhaler in the treatment of moderate persistent asthma. The patients were randomized to one of four treatment groups: MF DPI (100, 200, 400 microg b.i.d) or BUD Turbuhaler. 400 microg b.i.d in a 12-week, active-controlled, evaluator-blind, multicentre international trial. The primary efficacy variable was the mean change from baseline to endpoint (last treatment visit) in forced expiratory volume in one second (FEV1). Changes in FEV1 showed a statistically significant superiority (p<0.05) of MF DPI 200 and 400 microg b.i.d compared with the BUD Turbuhaler 400 microg b.i.d treatment. Significant superiority (p<0.05) was also seen in scores for several secondary efficacy variables when MF DPI was compared with BUD Turbuhaler treatment. MF DPI 200 microg b.i.d was comparable to MF DPI 400 microg b.i.d in therapeutic benefit. The incidence of oral candidiasis was no more than 3% in any group. All treatments were well tolerated. A total daily dose of 400 microg of mometasone furoate administered by dry powder inhaler provides a well-tolerated treatment for patients with moderate persistent asthma and results in a significantly greater improvement, when compared to a daily dose of 800 microg BUD Turbuhaler in the parameters measured in this study.

Topics: Adolescent; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Circadian Rhythm; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols; Safety; Single-Blind Method; Sleep; Time Factors

To determine the benefit of inhaled high dose budesonide combined with terbutaline in patients with severe asthma at high altitude.. 42 patients with severe asthma at high altitude were assigned in a randomized, double-blind fashion to receive either budesonide combined with terbutaline (budesonide group, 21 cases) or terbutaline with placebo (control group, 21 cases). Both groups received terbutaline delivered by a metered-dose inhaler in a dose of 2.5 mg. Budesonide delivered by a metered-dose inhaler in 1.2 mg in budesonide group and placebo managed by a specially prepared metered-dose inhaler in control group were administered after terbutaline treatment above procedures. Repeated once after 10 min. Before and after therapy, the scores of the activity of accessory respiratory muscles, dyspnea, wheezing (clinical index) and lung function were documented.. At 1, 2, 4, 6 h after therapy, FEV1% [(43 +/- +/- 5)%, (50 +/- 5)%, (57 +/- 5)%, (67 +/- 6)%], PEF% [(47 +/- 5)%, (55 +/- 6)%, (62 +/- 7)%, (69 +/- 7)%], clinical index (5.1 +/- 0.8, 4.3 +/- 0.6, 3.5 +/- 0.6, 2.5 +/- 0.4) in budesonide group and FEV1% [(42 +/- 5)%, (44 +/- 5)%, (45 +/- 5)%, (45 +/- 5)%], PFE% [(46 +/- 5)%, (47 +/- 5)%, (49 +/- 6)%, (49 +/- 6)%], clinical index (5.3 +/- 0.7, 5.0 +/- 0.5, 4.9 +/- 0.7, 4.8 +/- 0.7) in control group were difference markedly compared with before therapy [budesonide group was (35 +/- 5)%, (38 +/- 5)%, 8.3 +/- 1.0, and control group was (33 +/- 5)%, (38 +/- 5)%, 8.3 +/- 1.1, respectively], all (P < 0.01).. High dose of inhaled budesonide combined with terbutaline should be an effective therapy for patients with severe asthma at high altitude. Budesonide inhaled in high dose produces therapeutic effects as soon as 2 h after therapy.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Altitude; Asthma; Budesonide; Double-Blind Method; Female; Humans; Male; Respiratory Function Tests; Terbutaline

In a double-blind, cross-over study, we examined the effect of inhaled budesonide (800 microgram twice daily via Turbohaler) on lung function and various markers of airway inflammation including airway responsiveness to methacholine (PC20), exhaled nitric oxide (NO), eosinophils in induced sputum, bronchoalveolar lavage (BAL), and airway biopsies from 14 patients with mild asthma needing beta2- agonist therapy only. After inhaled steroids, there was a significant increase in FEV1 and PC20, and reduction in exhaled NO. Eosinophils in induced sputum and airway biopsy sections were also significantly decreased, although BAL eosinophil counts remained unchanged. At baseline, significant correlations were observed between exhaled NO and PC20 methacholine (r = 0.64, p < 0.05), exhaled NO and peak expiratory flow rate (PEFR) variability (r = 0. 65, p < 0.05), sputum eosinophils and FEV1 (r = -0.63, p = 0.05), and sputum eosinophils and log PC20 methacholine (r = -0.67, p < 0. 05). After treatment with inhaled steroids, there was a significant correlation between eosinophils in biopsy sections, and BAL, with log PC20 methacholine. It is likely that these parameters represent different aspects of the inflammatory process, which are all inhibited by inhaled steroids.

Topics: Administration, Inhalation; Adult; Asthma; Bronchi; Bronchitis; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Lung; Male; Methacholine Chloride; Peak Expiratory Flow Rate

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Budesonide; Double-Blind Method; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nasal Mucosa; Placebos; Stomatitis

Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States.. This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma. Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients.. Patients enrolled had an average duration of asthma of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo.. Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Treatment Outcome

The Childhood Asthma Management Program (CAMP) is a multicenter, randomized, double-masked clinical trial designed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma: budesonide (a glucocorticoid used daily) and albuterol (a short-acting beta-agonist bronchodilator used as needed); nedocromil (a nonsteroid anti-inflammatory agent used daily) and albuterol; and placebo and albuterol. One thousand forty-one children (32% from ethnic minority groups), aged 5 to 12 years at screening, are currently participating. The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second (FEV1) percent of predicted, observed over 5- to 6-year period. The trial also assesses differences between treatment groups with respect to airway responsiveness, morbidity, physical growth and development, and psychological growth and development. This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial.

Topics: Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Data Collection; Data Interpretation, Statistical; Double-Blind Method; Follow-Up Studies; Humans; Multicenter Studies as Topic; Nedocromil; Patient Selection; Quality Assurance, Health Care; Randomized Controlled Trials as Topic; Research Design; Sample Size

Salmeterol inhaled twice-daily is now being used more frequently as additional treatment in asthma insufficiently controlled by inhaled corticosteroids. We compared oral bambuterol in a dose of 20 mg taken once daily in the evening with inhaled salmeterol at 50 microgram taken twice daily in 126 asthmatic patients (60 bambuterol, 66 salmeterol) aged 18 to 74 yr who were treated for at least 4 wk with inhaled corticosteroids at a constant dose of 400 to 2,000 microgram/d or with oral corticosteroids at /= 15% overnight decrease in peak expiratory flow (PEF) on 3 of the preceding 7 d, in order to be randomized into this double-blind, double dummy, multicenter parallel group study (2-wk run-in period and 6 wk of treatment). There was no significant difference between bambuterol and salmeterol in morning change from baseline in PEF (p = 0.53). The median increases in morning PEF were 50 L/min for bambuterol and 55 L/min for salmeterol. Other variables (evening PEF, percent of overnight decrease in PEF, number of awakenings, percent of nights with an awakening, number of puffs of rescue medication, asthma symptoms during the day and night, and mean tremor score) also showed no significant difference between bambuterol and salmeterol. Both treatments, at the doses given, were well tolerated. Once-daily oral bambuterol is a convenient, effective, and less expensive alternative to twice-daily inhaled salmeterol for treating nocturnal asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Terbutaline

Subsensitivity of airway beta2-adrenoceptors develops readily in asthmatics receiving regular long-acting beta2-agonists. This subsensitivity may be rapidly reversed by using systemic corticosteroids. The purpose of the present study was to investigate whether the same acute facilitatory effects occur when using a bolus dose of inhaled corticosteroid.. Ten subjects with stable mild-to-moderate asthma, with a mean age of 27 years, mean (+/- SD) FEV1 of 2.95 L (0.94 L), 81% (15%) of predicted, all receiving inhaled corticosteroids, reactive to adenosine monophosphate (AMP) with a provocative concentration producing a 20% fall in FEV1 (PC20) < 200 mg/mL, were recruited into a randomized double-blind crossover study. The subjects received two separate 1-week treatment periods with formoterol dry powder, 24 microg bid, with an initial 1-week run-in and a 1-week washout period between the treatments. A single dose of placebo or budesonide turbuhaler, 1,600 microg, was taken in conjunction with the last dose of both treatment periods. AMP challenge was performed 2 h after the first and last dose of formoterol. Blood for lymphocyte beta2-adrenoceptor density (Bmax) was also measured before and after treatment with formoterol.. There was no significant difference in the geometric mean PC20 after the first dose of formoterol comparing the two treatment periods: 362 mg/mL vs 391 mg/mL. The PC20 after the last dose of formoterol was significantly higher (p < 0.05) in conjunction with budesonide than with placebo: 427 mg/mL vs 99 mg/mL, amounting to a 4.3-fold difference (95% confidence interval [CI], 1.1 to 16.6). For comparison within each treatment period, there was significant subsensitivity (p < 0.05) between the first and last dose of formoterol when the latter was given with placebo: 391 mg/mL vs 99 mg/mL, a 3.9-fold fall (95% CI, 1.0 to 15.2), but not when the latter was given with budesonide: 362 mg/mL vs 427 mg/mL, a 1.2-fold rise (95% CI, 0.5 to 2.8). Lymphocyte 02-adrenoceptor density (geometric mean Bmax: fmol/10(6) cells) also showed significant down-regulation (p < 0.05) by formoterol given with placebo: preformoterol 2.53 vs postformoterol 1.91, but not by formoterol given with budesonide: preformoterol 2.43 vs postformoterol 2.67. The Bmax was significantly higher (p < 0.05) with formoterol + budesonide as compared to formoterol + placebo, amounting to a 1.40-fold difference (95% CI, 1.09 to 1.80).. We have shown that a bolus dose of inhaled budesonide rapidly reverses subsensitivity to AMP bronchoprotection and associated beta2-adrenoceptor down-regulation in asthmatics taking regular formoterol. Further studies are indicated to assess whether high-dose inhaled corticosteroids should be administered as soon as possible along with beta2-agonists during an acute episode of bronchoconstriction.

Topics: Adenosine Monophosphate; Adrenergic beta-Agonists; Adult; Asthma; Bronchial Provocation Tests; Budesonide; Cross-Over Studies; Double-Blind Method; Down-Regulation; Drug Interactions; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Receptors, Adrenergic; Respiratory Mechanics; Spirometry

The aim of this study was to investigate whether budesonide, for 10 d, administered at the first sign of an upper respiratory tract infection, could reduce asthma symptoms in 1-3-y-old children with asthma during infections. The primary efficacy variable was symptom scores. The study had a multicentre, randomized, double-blind, placebo-controlled design with parallel groups. Fifty-five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask. Each child was monitored for 1 y. Budesonide was given 400 microg q.i.d. for the first 3 d and b.i.d. for 7 d. Symptoms (cough, wheeze, noisy breathing and breathlessness) were scored (0-3) daily by the parents. Asthma symptom scores were lower in children treated with budesonide than in those given placebo. The effect was most pronounced for cough and noisy breathing, but it did not affect the need for hospital care. In conclusion, treatment with budesonide, started at the first sign of a respiratory infection, reduced asthma symptoms in toddlers with episodic asthma.

Topics: Asthma; Budesonide; Child, Preschool; Double-Blind Method; Female; Glucocorticoids; Humans; Infant; Male; Respiratory Tract Infections; Treatment Outcome

Forty children aged 1-3 y completed a placebo-controlled study on the effects of 10 d of inhaled budesonide for asthma caused by respiratory tract infection. The effects on symptoms were significantly better in the active than in the placebo group. In 20 of these children the systemic effects of high-dose inhaled budesonide for 10 d and the effect of a 3-d course of oral betamethasone on asthma exacerbation were evaluated. Systemic effects were evaluated by measuring morning cortisol in serum and urine, and the bone markers osteocalcin, ICTP (the C-terminal telopeptide region of type I collagen) and PIIINP (an N-terminal propeptide of type III procollagen) in serum before and at the end (d 7-10) of treatment (1600 microg budesonide d(-1) for 3 d and 800 microg for 7 d). In 9 children, measurements were taken on d 3 of a 3-d course of betamethasone (6, 4 and 2 mg) for asthma exacerbation and 14 d later. There were no signs of systemic effects after 7-10 d of budesonide. After 3 d of betamethasone, serum cortisol decreased from a median of 263 to 26 nmol l(-1), urine cortisol/creatinine from 19.9 to 7.2 nmol l(-1), osteocalcin from 31.4 to 5.5 microg l(-1), ICTP from 19.4 to 8.5 microg l(-1) and PIIINP from 12.3 to 5.9 microg l(-1). Two weeks later, the levels were back to normal. In conclusion, short courses of oral betamethasone have pronounced systemic effects, whereas 10 d of high doses of budesonide do not produce significant systemic effects.

Topics: Asthma; Betamethasone; Biomarkers; Bronchodilator Agents; Budesonide; Child, Preschool; Collagen; Creatinine; Double-Blind Method; Glucocorticoids; Humans; Hydrocortisone; Infant; Osteocalcin; Peptide Fragments; Procollagen; Treatment Outcome

To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma.. Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment.. Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003).. FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index

Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever.. Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy.. Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol.. PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups.. Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Topics: Adolescent; Animals; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cats; Child; Desensitization, Immunologic; Double-Blind Method; Dust; Histamine Release; Humans; Immunoglobulin E; Immunoglobulin G; Mites; Pollen; Rhinitis, Allergic, Seasonal

We have previously shown that allergen inhalation by asthmatics is associated with increases in bone marrow eosinophil/basophil colony-forming cells (Eo/B-CFU), and increases in CD34(+) hemopoietic progenitors expressing the alpha-subunit of the IL-5 receptor (IL-5Ralpha). This study investigated the effect of inhaled corticosteroid on baseline numbers and allergen-induced increases in these parameters. Nine subjects with mild, stable asthma inhaled budesonide (400 microgram/d) for 8 d in a placebo-controlled, double-blind, randomized crossover study. On Day 7, subjects inhaled allergen, with bone marrow sampling before and 24 h after challenge. Budesonide inhalation significantly attenuated the allergen-induced early and late asthmatic responses, degree of increase in sputum and blood eosinophils, as well as the baseline numbers of total bone marrow CD34(+) cells (p < 0.05), CD34(+)IL-3Ralpha+ cells (p < 0.01) and IL-5-responsive Eo/B-CFU (p < 0.05). Allergen inhalation significantly increased Eo/B-CFU grown in the presence of IL-3, GM-CSF, or IL-5 alone (p < 0.05) and in combination (p < 0.01), as well as the number of CD34(+)IL-5Ralpha+ cells (p < 0.01). However, these increases in Eo/B-CFU and CD34(+)IL-5Ralpha+ cells were not affected by budesonide treatment. These data demonstrate that short-term inhaled budesonide treatment has a systemic effect in inhibiting the turnover of a subpopulation of bone-marrow-derived progenitors, but that inhalation of allergen overcomes this inhibitory effect.

Topics: Administration, Inhalation; Administration, Topical; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Basophils; Blood Cells; Bone Marrow; Budesonide; Eosinophils; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation; Male; Respiratory System; Sputum; Stem Cells

Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year.. A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 micrograms twice daily in 30 patients, and budesonide (BUD), 800 micrograms twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later.. There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not differ significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (r = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment.. There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Bone Density; Bone Development; Bone Resorption; Budesonide; Female; Femur Neck; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Spine

Guidelines for asthma management focus on treatment with inhaled corticosteroids and on home recording of peak expiratory flow (PEF). The effect of maintenance treatment with inhaled corticosteroids on PEF variation and its relation to other parameters of disease activity were examined in 102 asthmatic children aged 7-14 years.. During 20 months of treatment with inhaled salbutamol, with or without inhaled budesonide (600 micrograms daily), forced expiratory volume in one second (FEV1), the dose of histamine required to provoke a fall in FEV1 of more than 20% (PD20), the percentage of symptom free days, and PEF variation were assessed bimonthly. PEF variation was computed as the lowest PEF as a percentage of the highest PEF occurring over 14 days, the usual way of expressing PEF variation in asthma self-management plans. For each patient using inhaled corticosteroids within subject correlation coefficients (rho) were computed of PEF variation to the percentage of symptom free days, FEV1, and PD20.. PEF variation decreased significantly during the first two months of treatment with inhaled corticosteroids and then remained stable. The same pattern was observed for symptoms and FEV1. In contrast, PD20 histamine continued to improve throughout the whole follow up period. In individual patients predominantly positive associations of PEF variation with symptoms, FEV1, and PD20 were found, but the ranges of these associations were wide.. During treatment with inhaled corticosteroids the changes in PEF variation over time show poor concordance with changes in other parameters of asthma severity. When only PEF is monitored, clinically relevant deteriorations in symptoms, FEV1, or PD20 may be missed. This suggests that home recording of PEF alone may not be sufficient to monitor asthma severity reliably in children.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Airway Obstruction; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Child; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Long-Term Care; Male; Peak Expiratory Flow Rate

It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma. To ensure that inflammation is suppressed whilst using the lowest possible dose, a sensitive and specific method for assessing airway inflammation is needed.. The usefulness of exhaled nitric oxide (NO), sputum eosinophils, and methacholine airway responsiveness (PC20) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid (budesonide via Turbohaler) were compared. Mild stable steroid naive asthmatic subjects were randomised into two double blind, placebo controlled studies. The first was a parallel group study involving three groups receiving either 100 micrograms/day budesonide (n = 8), 400 micrograms/day budesonide (n = 7), or a matched placebo (n = 6). The second was a crossover study involving 10 subjects randomised to receive 1600 micrograms budesonide or placebo. The groups were matched with respect to age, PC20, baseline FEV1 (% predicted), exhaled NO, and sputum eosinophilia.. There were significant improvements in FEV1 following 400 micrograms and 1600 micrograms budesonide (11.3% and 6.5%, respectively, p < 0.05). This was accompanied by significant reductions in eosinophil numbers in induced sputum (0.7 and 0.9 fold, p < 0.05). However, levels of exhaled NO were reduced following each budesonide dose while PC20 was improved only with 1600 micrograms budesonide. These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum. There were dose dependent changes in exhaled NO, sputum eosinophils, and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 micrograms daily.. Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation. This, however, requires further studies involving a larger number of patients.

Topics: Administration, Inhalation; Adult; Asthma; Bronchodilator Agents; Budesonide; Cell Count; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Male; Nitric Oxide; Sputum; Vital Capacity

Although many asthmatic patients are treated with a combination of beta2 agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta2 agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken.. Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 microg twice daily), terbutaline (500-1000 microg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment.. Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo = 2.05; terbutaline = 2.13; budesonide = 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) l/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) l/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness.. In this group of mild to moderate asthmatic subjects the combination of beta2 agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta2 agonist treatment impaired the beneficial effect of inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Terbutaline; Treatment Outcome

Inhaled corticosteroids and beta agonists are the most commonly used treatments in asthma and are often used together. Recent evidence suggests that many of the anti-inflammatory actions of corticosteroids are mediated by cross-talk between the activated glucocorticoid receptor (GR) and other transcription factors such as the pro-inflammatory nuclear factor kappa B (NFkappaB). Beta agonists can activate the transcription factor cAMP response element binding protein (CREB). A mutual inhibition between GR and CREB occurs in vitro which raises the possibility of a negative interaction between corticosteroid and beta agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with beta2 agonists and corticosteroids in asthma.. Seven subjects who were participating in a randomised, placebo controlled, crossover study of six weeks treatment with inhaled budesonide (400 microg twice daily), terbutaline (1 mg four times daily), and combined treatment were recruited. Biopsy samples of the bronchial mucosa were obtained after each treatment and analysed for the DNA binding activity of GR, CREB, and NFkappaB.. Budesonide increased GR activity (p<0.05) and decreased NFkappaB activity (p<0.05). No treatment combination altered CREB activity and terbutaline had no significant effects on any transcription factor.. Inhaled corticosteroids have significant effects on GR and NFkappaB activity in bronchial mucosa. A negative interaction between inhaled corticosteroids and beta agonists was not found.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchi; Budesonide; Cross-Over Studies; Cyclic AMP Response Element-Binding Protein; Drug Interactions; Humans; Middle Aged; NF-kappa B; Receptors, Glucocorticoid; Respiratory Mucosa; Terbutaline; Transcription Factors

Budesonide (Pulmicort) is an inhaled corticosteroid with high topical potency but low systemic activity. Turbuhaler is a novel breath-actuated, multi-dose, dry-powder inhaler.. This study was conducted to determine the efficacy and safety of two different dose regimens of budesonide Turbuhaler, compared with placebo, in adult patients with mild-to-moderate asthma not well-controlled with bronchodilator therapy.. This double-blind, randomized, placebo-controlled, parallel-group, multicenter study compared the efficacy and safety of 200 microg and 400 microg of budesonide, administered twice daily via Turbuhaler, with placebo, in 273 adult patients (aged 19 to 70 years) with mild-to-moderate asthma (FEV1 67% of predicted normal), not well-controlled with bronchodilator therapy. Efficacy was assessed by pulmonary function tests and patient assessments of asthma symptom control. Safety was assessed in terms of adverse events, laboratory evaluations, and physical examinations.. Two hundred and 400 microg of budesonide bid were significantly more effective than placebo at improving morning PEF (mean differences from placebo of 43.63 L/min and 40.10 L/min, respectively; P < .001) and FEV1 (mean differences from placebo of 0.44 L, and 0.50 L, respectively; P < .001) over the 12-week treatment period. Onset of action as assessed by morning PEF was within two days. Basal and stimulated plasma cortisol concentrations were not significantly affected by budesonide treatment compared with placebo.. Treatment of adults suffering from mild-to-moderate asthma with budesonide Turbuhaler is well tolerated and results in a rapid onset of asthma control which is maintained over time.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Placebos; Severity of Illness Index; Therapeutic Equivalency

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.

Topics: Aerosols; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Drug Delivery Systems; Filtration; Humans; Infant; Masks; Nebulizers and Vaporizers

Relapses of acute asthma following emergency department (ED) discharge can be reduced with systemic corticosteroid treatment. However, whether inhaled corticosteroids (ICSs) provide additional benefit is not known. Objective To determine whether the addition of ICSs to oral corticosteroid treatment would reduce relapses in patients with acute asthma discharged from the ED.. Placebo-controlled, double-blind, randomized clinical trial conducted in a community teaching hospital ED in Canada between November 1995 and September 1997, with a 21-day follow-up.. A total of 1006 consecutive patients aged 16 to 60 years presented to the ED with acute asthma; after excluding those using oral and/or inhaled corticosteroids as well as those meeting other exclusion criteria, 188 were included in the study.. Patients were discharged with a nontapering course of oral prednisone (50 mg/d) for 7 days. In a double-blind fashion, patients were randomly assigned to 1600 microg/d of inhaled budesonide (n = 94) or identical placebo (n = 94) for 21 days.. Incidence of relapse, defined as an unscheduled visit for worsening asthma symptoms, in budesonide vs placebo groups. Secondary outcomes included response to the Asthma Quality of Life Questionnaire, beta2-agonist use, symptom score, global asthma improvement assessment, and pulmonary function.. Five patients in the budesonide group and 3 in the placebo group either dropped out or were lost to follow-up but were included in primary analyses. After 21 days, 12 (12.8%) of 94 patients in the budesonide group experienced a relapse compared with 23 (24.5%) of 94 in the placebo group, a 48% relapse reduction (P=.049). Asthma Quality of Life Questionnaire scores were higher (better quality) in the budesonide group (P=.001), as well as for all domain scores (P=.001 to .01). Fewer beta2-agonist activations were used at the end of the trial by patients receiving budesonide (2.4/d vs 4.2/d; P=.01). Symptom scores (P=.001 to .004) and self-assessed asthma improvement scores (based on a 7-point Likert scale) (6.2 vs 5.2; P<.001) were higher (indicating fewer symptoms) for budesonide vs placebo. There were no differences in pulmonary function between the groups (peak expiratory flow rate: budesonide, 437 vs placebo, 453 L/min; P= .39) at 21 days. Using this approach, as few as 9 patients would require budesonide to prevent 1 relapse.. Patients discharged from the ED following treatment for acute asthma benefit from added treatment with high-dose inhaled budesonide for 21 days compared with oral corticosteroids alone.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Emergency Medical Services; Female; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prednisone; Recurrence; Respiratory Function Tests; Sickness Impact Profile

Recent investigations revealed that in patients with bronchial asthma the same anti-inflammatory effect is achieved by inhalation of half the dose of budesonide by a Turbuhaler (i.e. by using corticosteroid in powder form) as by a full dose of beclomethasone driven into the lungs by compressed chlorofluorocarbons (i.e. MDI = pressure dosage inhalator). The objective was to assess whether there is a difference between 12-week treatment with budesonide Turbuhaler in a smaller dose of 400 micrograms/day and treatment with beclomethasone dipropionate MDI 800 micrograms/day.. After an initial two-week period of the 227 patients with mild or medium severe asthma who had not taken corticosteroids for three months, into the budesonide Turbuhaler group 94 patients were included and into the beclomethasone MDI group 99 patients. Characteristics: group treated with budesonide (46 men, 48 women, mean age 38 years, FEV1 78% of appropriate values). Group treated with beclomethasone (51 men, 48 women, mean age 39 years, FEV1 81.5% of appropriate values). Morning and evening values of the peak expiration rate (PEF) increased significantly after budesonide treatment 2 x 200 micrograms/day) as compared with beclomethasone treatment (2 x 400 micrograms/day). Differences of morning PEF between budesonide and beclomethasone: 47:28 l/min, p < 0.05, differences of evening PEF: 32:10 l/min., p < 0.027. The number of dyspnoic attacks declined after both types of treatment, as well as the amount of inhaled bronchodilatating substances (terbutalin Turbuhaler). The differences between drugs were however not statistically significant.. Budesonide Turbuhaler, 400 micrograms/day when administered to patients with bronchial asthma was at least as effective as beclomethasone MDI, 800 micrograms/day. The increase of morning and evening PEF values was after budesonide significantly higher than after beclomethasone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Humans; Male; Middle Aged

We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate

Optimal management of chronic, mild-to-moderate asthma with inhaled steroids may include use of the lowest possible doses, as recommended in guidelines, and a reduction in the frequency of daily administration for greater convenience. Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials.. The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma.. Once daily budesonide was assessed in 309 adult subjects, including those who were and were not using an inhaled steroid at baseline. The subjects were stratified by inhaled steroid use and randomly assigned to one of 3 treatments: 200 microgram budesonide, 400 microgram budesonide, or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks. Beyond this point, treatment was continued unchanged for another 12 weeks (maintenance) in those receiving 200 microgram budesonide once daily and placebo. In those who received 400 microgram budesonide once daily, the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks (400/200 microgram group). Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow.. Once daily budesonide was well tolerated and resulted in significant improvements in all efficacy endpoints, even though baselines were well stabilized. Baseline lung function was elevated with little room for improvement; however, mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups, respectively, versus a decrease of -0.09 L in the placebo arm (P <.001). Results for peak expiratory flow were similar. Significant improvements in secondary endpoints, including symptoms, beta-agonist use, and quality of life, also developed with budesonide 200 and 400 microgram once daily.. Inhaled budesonide, in doses as low as 200 microgram, may be an appropriate introductory or maintenance dose in subjects with stable, mild-to-moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Inflammatory Agents; Asthma; Bronchial Spasm; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Respiratory Tract Infections

This study evaluated the efficacy and safety of four dosing regimens of budesonide inhalation suspension in children ages 6 months to 8 years with moderate persistent asthma.. This 12-week, randomized, double-blind, placebo-controlled, parallel-group study involved 481 children at 38 centers throughout the United States. Active treatment groups were budesonide inhalation suspension .25 mg once daily (QD), .25-mg two times daily (BID), .5-mg BID, or 1-mg QD. Efficacy was assessed by recording nighttime and daytime asthma symptoms, use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Objective measures of pulmonary function were assessed in children who were capable of consistently performing pulmonary function tests; peak expiratory flow (PEF) measurements were recorded twice daily on diary cards, and spirometry was recorded at clinic visits.. Baseline patient demographics, nighttime and daytime symptom scores, and pulmonary function data were similar across placebo and budesonide treatment groups. The majority of patients were male (64%) with a mean age of 55.0 +/- 26.3 months. The mean duration of asthma was 34.2 +/- 22.9 months, and mean baseline forced expiratory volume in 1 second (FEV1) was 79.8% of predicted, with 29.1% reversibility. Significant improvements in nighttime and daytime asthma symptoms scores were observed in budesonide treatment groups, compared with placebo. The mean change from baseline to week 0-12 for nighttime and daytime asthma symptom scores was significantly greater for the .25-mg BID, .5-mg BID, and 1-mg QD budesonide treatment groups, compared with placebo; significant clinical improvement was observed by the second week of treatment. The lowest budesonide dose used (.25 mg QD) resulted in numerical improvements in symptom scores that were not statistically significant when compared to placebo. Significant improvements in morning PEF were observed in all budesonide treatment groups, except for the .25-mg QD group, compared with placebo. All treatment groups showed numerical improvement in FEV1, but only the .5-mg BID dose was significantly different from placebo.. The results of this study demonstrate that budesonide inhalation suspension is effective and well tolerated for infants and young children with moderate persistent asthma. Budesonide inhalation suspension is an important therapeutic option for young children who are not able to use other available delivery devices.

Topics: Administration, Inhalation; Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Respiratory Function Tests; United States

Although some studies suggest that asthma deteriorates after reducing inhaled steroids, results of long-term studies indicate that this might not be true for all patients. The aim of this study was to determine the utility of the detection of a plateau on the concentration-response curves to inhaled methacholine as a marker for safely reducing the dose of inhaled budesonide in asthmatic patients who are well-controlled with a moderately high dose of this inhaled steroid. A total of 46 patients with moderate asthma, well-controlled for at least 6 months by treatment with 800 microg budesonide daily, were included in the study. Subjects were treated for a 2-week run-in period with their usual dose of budesonide. At the end of the run-in, all subjects were challenged with methacholine (0.095-200 mg x mL(-1)). Plateau responses, median effective concentration values, slopes and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) values were measured. For the subsequent 12 weeks, patients were treated in an open design with budesonide at a reduced dose (200 microg once daily), and were asked to record their peak expiratory flow (PEF) in the morning and in the evening. In addition, asthma symptoms and use of rescue terbutaline were recorded in diaries. Plateaus were present in 24 patients, whereas 22 subjects showed concentration-response curves without evidence of a plateau. Ten patients in the nonplateau group deteriorated after reducing inhaled budesonide, compared to one patient in the plateau group (p = 0.002). In the nonplateau group, FEV1 decreased from a baseline value of 3.28+/-0.19 L to 2.94+/-0.20 L at week 12 (p<0.0001). Likewise, morning PEF decreased from 419+/-19 L x min(-1) at baseline to 394+/-19 L x min(-1) at week 12 (p = 0.02). By contrast, these variables remained unchanged in the plateau group. In conclusion, in asthmatic patients, well-controlled with a moderately high dose of budesonide, the detection of a plateau on the concentration-response curve to inhaled methacholine may be used as a marker for safely reducing the corticosteroid dose.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Peak Expiratory Flow Rate

Inhaled glucocorticosteroids such as budesonide have an important role in the management of asthma. Although these agents have traditionally been given twice daily, evidence is accumulating that once-daily treatment may be as effective as twice-daily administration. The efficacy of budesonide Turbuhaler (Astra, Lund, Sweden), 400 micrograms once daily in the evening or 200 micrograms twice daily, was compared in a randomized, double-blind study involving 181 patients (75 men, 106 women; mean age 30.8 years) with mild asthma [mean forced expiratory volume in 1 s (FEV1) 92.8% pred.] who had not previously been treated with inhaled glucocorticosteroids. After a 2-week run-in period, patients were randomized to either regimen and treated for 6 weeks. This was followed by two 8-week open treatment periods, during which all patients received budesonide Turbuhaler, 200 micrograms once daily during the first period and 100 micrograms once daily during the second period. The mean change in morning peak expiratory flow (PEF) during the double-blind treatment period was 16.9 l min-1 in patients receiving once-daily treatment and 17.2 l min-1 in those receiving twice-daily treatment. Similarly, there were no significant differences in evening PEF, symptom scores, bronchodilator use or spirometry data between patients receiving once- and twice-daily treatments. The improvements in morning PEF, symptom scores and bronchodilator use seen during the double-blind treatment period were maintained during the two open treatment periods. It is concluded that once-daily treatment with budesonide Turbuhaler is as effective as an initial therapy twice-daily treatment in patients with mild persistent asthma and that the initial dose can be reduced to maintenance levels (including 100 micrograms) without loss of asthma control.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome

Leptin, a 167-amino-acid peptide, is a recently discovered hormone which is believed to play a major role in the regulation of body weight. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with asthma treated with inhaled budesonide 800 micrograms day-1. Ten boys and three girls with asthma, all adolescents aged from 12.9 to 16.6 years, were studied in a randomized double-blind two-period cross-over trial with 4-week treatment periods and a 1-week wash out. Placebo was given during one period and 800 micrograms budesonide during the other via a 750 ml volume spacer (Nebuhaler, Astra Draco, Lund, Sweden). On the last day of the placebo and budesonide periods blood samples were taken and serum leptin was measured by a specific radioimmunoassay. The difference in mean (SEM) leptin concentration between the budesonide and placebo period was 0.2 (0.4) microgram l-1 (P = 0.71; t = -0.4; df = 12, 95% confidence interval -0.9-0.7 microgram l-1). Inhaled budesonide 800 micrograms per day from a Nebuhaler does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected.

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Appetite; Asthma; Biomarkers; Body Weight; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Leptin; Male; Proteins

Children's use of inhalation devices can give valuable information about their adherence to asthma therapy. The aim of this study was to examine treatment adherence of low dose inhaled budesonide or placebo administered via Turbuhaler twice daily in children with mild asthma participating in an asthma trial, by comparing diary registration with the number of doses remaining in the inhaler. A total of 163 children (age 7-16 yrs, 56 females, 107 males) with mild asthma (mean baseline forced expiratory volume in one second (FEV1) was 103% of predicted), were included into a double blind, randomized study. After a two-week run-in period, the children received inhaled budesonide, either 100 microg or 200 microg daily, and/or placebo for 12 weeks. All patients used daily diary cards throughout the study. Results from 161 patients were analysed. Mean compliance according to the diary was 93%, whereas estimated mean compliance when counting remaining doses in the Turbuhaler was 77%. Overuse of medication was found in 7% of the children. There was no significant difference in compliance between sex in the study group, whereas children aged < or =9 yrs had significantly better drug adherence than older children. No significant relationship was found between symptom score and compliance. In conclusion, even with optimal patient follow-up in a clinical trial, adherence to prophylactic asthma treatment is considerably lower than the patients own reports from the use of daily diary cards.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Nebulizers and Vaporizers; Patient Compliance; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome

Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects.. To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily.. Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication.. After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications.. These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Reference Values; Triamcinolone Acetonide; Volunteers

The aim of the present study was to compare the output of a breath-synchronized jet nebulizer to a conventional constant output nebulizer over a fixed period of time in terms of inhaled mass of budesonide, i.e., the amount of budesonide deposited on a filter interposed between the nebulizer and the face mask. One hundred and sixty-five asthmatic children (103 boys) were enrolled in this open, randomized, crossover trial. Their age ranged from 6 months to 7.9 years, height from 69 to 132 cm, and weight from 8.2 to 31.3 kg. Their duration of asthma ranged from less than 1 to 7 years. Budesonide suspension, 0.5 mg mL-1, 2 mL, was used. With 5 min of constant output nebulization, the mean inhaled mass of budesonide in percent of the nominal dose was 11.4% in the youngest children and 14.9% in the 7-year-old children. Expressed in percent of the total output of budesonide, i.e., the amount that left the nebulizer as an aerosol, the inhaled mass ranged from 34.6-48.6%. Thus, 51.4-65.4% of the total output was deposited on the expiratory filter. With 5 min of breath-synchronized nebulization, the mean inhaled mass ranged from 10.5-14.9% of the nominal dose. For the youngest patients less than 3-4 years of age, it was approximately 80-90% of the total output. For the older patients the inhaled mass was approximately 95% of the total output, i.e., only small amounts of budesonide were deposited on the expiratory filter. For both modes of nebulization the between-subject variation in inhaled mass was large: up to 6-fold in the young children and 3-4-fold in the older ones. The results of the present study showed that the inhaled mass of budesonide was significantly age-dependent with both modes of nebulization, i.e., the inhaled mass was less in younger children. Breath-synchronized nebulization resulted in reduced waste of drug during expiration.

Topics: Administration, Inhalation; Age Factors; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Equipment Design; Female; Filtration; Humans; Infant; Male; Nebulizers and Vaporizers; Respiration; Tidal Volume

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone early in the emergency room management of acute asthma, we conducted a double-blind, placebo-controlled trial. Eighty children, 2 years to 12 years of age, with acute moderate attacks of asthma, were randomized into two groups. One group received nebulized salbutamol (0.15 mg/kg) and placebo at half-hourly intervals for three doses, and a single dose of oral prednisolone (2 mg/kg) (prednisolone group) and other group received three doses of nebulized salbutamol and budesonide (800 microg) at half-hourly intervals and a single dose of placebo tablets (budesonide group). The baseline characteristics of the two groups were similar, but after three doses of nebulization oxygen saturation, respiratory rate, pulmonary index and respiratory distress score were significantly improved in the budesonide group compared to prednisolone group (p < 0.01). The proportion of patients who were fit for discharge at the end of 2 h after the third dose of nebulization was significantly higher in the budesonide group than in the prednisolone group (22/ 41, 54% vs 7/39, 18%, p < 0.001). The data suggest that a combination of nebulized salbutamol and budesonide should be preferred in the emergency room management of children with acute moderate to severe exacerbation of asthma and who are not on prior oral or inhaled steroid therapy.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-Agonists; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Prednisolone; Respiratory Function Tests

The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.

Topics: Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Prednisolone

Inhaled glucocorticosteroids (GCS) are the most effective long-term controller medications for the treatment of persistent asthma. Currently, however, available delivery devices limit their use in young children. A nebulized formulation of budesonide has been developed to address the needs of infants and young children.. To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS.. Three hundred fifty-nine children were randomized to receive once-daily budesonide inhalation suspension (0.25 mg, 0.50 mg, or 1.0 mg) or placebo via a Pari LC-Jet Plus nebulizer for 12 weeks. Efficacy assessments included nighttime/daytime asthma symptoms, pulmonary function (subset of patients), rescue medication use, and treatment discontinuations. Safety was based on adverse events and assessment of HPA-axis function.. Demographics, baseline characteristics, asthma symptoms, and pulmonary function were similar across treatment groups. Mean nighttime/daytime asthma symptom scores were 1.19 +/- 0.63 and 1.34 +/- 0.53, respectively. Mean duration of asthma was 36.3 months and mean FEV1 was 81.3% of predicted with 27.7% reversibility. Following 12 weeks of treatment, all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms (P < or = .049) and significant decreases in rescue medication use (P < or = .038) compared with placebo. Significant improvements (P < or = .044) in FEV1 were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups. There were no differences between doses of budesonide inhalation suspension. Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups.. Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments.

Topics: Administration, Inhalation; Asthma; Budesonide; Child; Child, Preschool; Circadian Rhythm; Double-Blind Method; Female; Humans; Infant; Male; Respiratory Function Tests; Suspensions

The present pharmacokinetic study was undertaken to determine the dose proportionality of three different doses of budesonide-400 microg, 800 microg or 1600 microg administered twice daily by a dry-powder inhaler (Turbuhaler ) in adult patients with mild asthma.. A total of 38 patients received budesonide by inhalation, 13 received 400 microg twice daily, 12 received 800 microg twice daily and 13 received 1600 microg twice daily. Mean FEV1 at inclusion was 3.4, 4.0 and 3.9 l min-1 in the three groups, respectively. Blood samples were taken after a single dose, and after 3 weeks of daily treatment, for pharmacokinetic evaluation. Plasma concentrations of budesonide were determined by liquid chromatography plus mass spectrometry.. Eleven evaluable patients remained in each dose group. Mean time to peak budesonide plasma concentration (tmax ) was short (0.28-0.40 h) and did not differ between treatment groups. Budesonide concentrations declined rapidly thereafter, indicating efficient pulmonary absorption and rapid elimination with a half-life of approximately 3 h. Cmax was 1. 4(2.0) nmol l-1 (single (repeated) doses), 2.6(3.6) nmol l-1 and 5. 4(6.4) nmol l-1 after 400, 800 and 1600 microg twice daily, respectively. The corresponding results for the area under the plasma concentration vs time curve (AUC) were 271(325), 490(628) and 915(1096) nmol l-1 min. Ninety percent confidence intervals for pairwise dose-normalized Cmax and AUC comparisons between groups were large but contained unity in all cases, thus indicating dose-proportional pharmacokinetics. Regression on analysis supported these findings. Mean AUC after repeated doses (AUC(0,12 h,RD)) was on average 23% higher than the mean AUC after single doses (AUC(0, infinity,SD)(P=0.04) with no significant differences between doses, indicating slight accumulation following bid dosing.. In this relatively small study, budesonide inhaled via Turbuhaler appeared to have dose-proportional pharmacokinetics, both within and above the clinically recommended dose range for asthmatic patients.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Male; Middle Aged; Powders

Previous reports suggest that regular use of beta-agonists does not lead to tolerance to their bronchodilator effects. However, most studies have been conducted in stable asthma. This study investigates whether bronchodilator tolerance can be demonstrated during acute bronchoconstriction. Thirty-four asthmatic subjects were treated with 6 weeks inhaled terbutaline (1 mg q.i.d.), budesonide (400 microg, b.i.d.), both drugs or placebo in a randomized, double-blind, cross-over study. After each treatment methacholine was administered to induce a 20% fall in the forced expiratory volume in one second (FEV1). The response to inhaled salbutamol 100, 100, 200 microg at 5 min intervals) was then measured. Dose-response curves were compared using an analysis of covariance. Pre-methacholine FEV1, the highest pre-methacholine FEV1, the fall in FEV1 induced by methacholine and the logarithm of the provocative dose of methacholine required to induce the 20% fall in FEV1 (PD20) were used as covariates. There was a significantly reduced response to salbutamol after 6 weeks terbutaline treatment: the mean (95% confidence intervals (CI)) area under the dose-response curve was reduced by 36% (24, 47) compared to placebo (p<0.0001). The reduction in bronchodilator response was not affected by concomitant treatment with budesonide. Significant tolerance to the bronchodilator effect of inhaled beta-agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled beta-agonists may lead to a reduced response to emergency beta-agonist treatment during asthma exacerbations.

Topics: Acute Disease; Adolescent; Adrenergic beta-Agonists; Adult; Airway Obstruction; Albuterol; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Terbutaline

Because of the challenges associated with conducting clinical trials in pediatric patients, most drugs have not been adequately tested in this patient population. Insufficient testing frequently results in product labeling that fails to provide instructions for safe and effective use in pediatric patients. The most prevalent chronic disease in children is asthma; however, very few asthma medications have been evaluated in infants and young children. Budesonide inhalation suspension is an anti-inflammatory corticosteroid administered by nebulization that requires only passive inhalation and is therefore suitable for infants and young children who are unable to use currently available inhalation devices for the administration of asthma medications. The efficacy of budesonide inhalation suspension was evaluated in 3 US clinical trials. All 3 trials were randomized, controlled, double-blind, 12-week studies in children (6 months-8 years of age) with a primary diagnosis of chronic persistent asthma. Symptom assessments conducted in both the morning and evening were the primary efficacy variables. Although the children were young, secondary efficacy evaluations included spirometry and peak expiratory flow collected in both the morning and evening (in a subset of patients capable of performing these maneuvers). Patients who completed or were discontinued from the 12-week double-blind treatment phase were eligible to enter 52-week, open-label extension studies. The design of these 3 studies confirms the feasibility of the performance of placebo-controlled clinical trials of asthma medications in pediatric patients and allows for efficacy evaluations based on symptom assessments together with pulmonary function testing.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Placebos; Suspensions

This paper reviews the results from 3 randomized, double-blind, placebo-controlled, multicenter studies that assessed the efficacy and safety of once- and twice-daily dosing of budesonide inhalation suspension (BIS) in infants and young children with persistent asthma. In children with mild persistent asthma that was previously treated with bronchodilators or noncorticosteroid anti-inflammatory agents (study A), nighttime and daytime asthma symptoms were significantly improved in 0.25-mg once daily, 0.5-mg once daily, and 1.0-mg once daily BIS treatment groups compared with placebo (P

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Circadian Rhythm; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Infant; Male; Peak Expiratory Flow Rate; Placebos; Severity of Illness Index; Suspensions; Treatment Failure

This article reviews the short-term and long-term safety profile of budesonide inhalation suspension (BIS) for nebulization in infants and young children with persistent asthma. Short-term safety (12 weeks) was assessed by pooling the results from the 3 randomized, double-blind, placebo-controlled, multicenter studies (studies A, B, and C) on the efficacy and safety of once- and twice-daily BIS. Long-term safety of BIS and conventional asthma therapy (CAT) was assessed in 52-week extension studies of the 12-week double-blind trials. CAT consisted of any available therapy for asthma; in 2 studies, CAT could have included treatment with inhaled glucocorticosteroids. Safety was assessed by monitoring adverse events (AEs), physical examinations, and basal and ACTH-stimulated plasma cortisol levels (in a subset of subjects). In the 52-week open-label extensions, the effects of BIS on growth velocity and skeletal age also were determined. In the 12-week studies, a total of 1017 subjects was evaluated for safety; totals of 231, 185, 229, 327, and 45 subjects were randomized to receive placebo or BIS at total daily doses of 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively. Subject demographics and baseline asthma characteristics were similar across treatment groups, except that age, weight, height, and duration of asthma appeared higher in the 2. 0-mg daily dose group. For BIS groups, mean age was 58.9 months; mean weight was 20.3 kg; mean height was 108.9 cm, and mean duration of asthma was 3.2 years. There were no differences in the incidence, severity, or types of AEs reported among the BIS and placebo groups. There were no significant differences between placebo and BIS treatment groups in basal or ACTH-stimulated cortisol levels, physical examinations, clinical laboratory values, or fungal cultures. A total of 670 subjects completed the 52-week extension studies; 223 subjects received CAT and 447 received BIS. Median total daily doses of BIS ranged from 0.50 mg to 1.0 mg in the 3 studies, and the mean duration of treatment exposure was 304 +/- 119 days and 342 +/- 83 days in CAT and BIS groups, respectively. During the 52-week treatment period, the incidences of reported AEs were comparable between treatment groups and were mild-to-moderate in intensity; no new AEs occurred during the 52-week studies compared with 12-week studies. No significant differences were observed between BIS and CAT in basal or ACTH-stimulated cortisol levels, physical examinations,

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Growth; Humans; Hypothalamo-Hypophyseal System; Infant; Male; Nebulizers and Vaporizers; Pituitary-Adrenal System; Placebos; Time Factors

Many biological processes give outcome data which show a curvilinear association with time which tends to an asymptote. We show how autoregressive models can be used to describe this association within individual subjects. We also present a Bayesian approach implemented using statistical software, BUGS, to fit these models in a multi-level (hierarchical) setting that describes variation in the association between subjects. Peak expiratory flow data from a clinical trial involving subjects with asthma are used to illustrate the methods.

Topics: Anti-Inflammatory Agents; Asthma; Bayes Theorem; Budesonide; Computer Simulation; Humans; Linear Models; Models, Biological; Numerical Analysis, Computer-Assisted; Peak Expiratory Flow Rate; Software; Time Factors; Treatment Outcome

We evaluated the efficacy of once-daily versus twice-daily treatment with budesonide, delivered by a Turbuhaler(R), in the management of children with stable asthma in a randomized, double-blind, parallel-group study involving 206 children (age 5-15 years). After a 2-week run-in period during which the children were maintained on their usual dose of budesonide (200 microg or 400 microg/day), patients were randomized to receive the same daily dose in either two daily administrations (morning and evening) or as a single dose in the morning over a period of 12 weeks. The primary efficacy variable was morning peak expiratory flow (PEF). The mean morning PEF during the run-in phase was 271 L/min in patients randomized to once-daily treatment and 264 L/min in those randomized to twice-daily treatment. The mean change from baseline to the last 2 weeks of the treatment period in the two groups was -0.3 L/min (95% confidence limits -6.6 to +6.0) and 2.5 L/min (-4.3 to +9.3). The estimated difference between the groups was -2.8 L/min, with 90% confidence limits of -10.4 + 4.5; these were close to the limits regarded as indicative of equivalence (-10 to +10), and hence the difference was not regarded as clinically relevant. Similarly, there were no significant differences between the groups in regard to secondary efficacy measures such as spirometric tests and symptom scores. Both treatments were well tolerated. We conclude that once-daily administration of budesonide by Turbuhaler(R) is as effective as twice-daily treatment in the management of stable asthma in children treated with inhaled steroids at doses of 200-400 microg/day.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 micrograms daily via a Diskhaler inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 micrograms daily via a Turbuhaler inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma. FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0.02), the incidence of days free from rescue bronchodilator usage (P = 0.02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0.04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5-16, for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17-24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33.8 and 28.4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11.0 vs. 14.7 days; P = 0.035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18.5 vs. 23.6 days; P = 0.12), the time off work was reduced (4.2 vs. 7.6 days; P = 0.012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 l min-1; P = 0.07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses. The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Propionates; Treatment Outcome; Vital Capacity

To evaluate the efficacy of aerosolized budesonide therapy (with metered dose inhaler and spacer) early in the emergency room treatment of acute moderate exacerbations of bronchial asthma in children.. Randomized, double-blind, placebo-controlled trial.. Paediatric Emergency Service of an urban teaching hospital and a tertiary case referral centre.. Sixty children between 3 and 12 years of age with an acute moderate exacerbation of asthma.. All patients received humidified oxygen (5-8 L/min by Venturi(R) mask; Hudson Respiratory Care, Temecula, CA, USA), nebulized salbutamol (0.15 mg/kg in 3 mL saline) and were randomized to receive either budesonide (400 microg) or placebo inhalation (MDI and spacer) at half hourly intervals for three doses. If there was an inadequate response or no response to treatment at the end of 2 h, oxygen and salbutamol therapy were continued and the patient was given one of dose intravenous hydrocortisone and was started on an aminophylline infusion. If there was no response at the end of a further 4 h, the patient was hospitalized. INITIAL EVALUATION AND MONITORING: Colour, respiratory rate (RR), heart rate, accessory muscle usage, chest retraction, wheeze, oxygen saturation (by pulse oximetery) and peak expiratory flow rate (PEFR) was recorded at admission and thereafter at hourly intervals for 3 h or until till the child recovered. The need for oxygen therapy after 2 h and need for hospitalization were recorded.. Both groups showed a significant improvement in respiratory status at the end of 2 h. However, children in the intervention group showed greater improvements in RR and PEFR (P < 0. 05) and respiratory distress score (P < 0.1). A significantly lower proportion of the intervention group patients required oxygen therapy for more than 2 h (23% vs 50%; P < 0.05) and aminophylline infusion and systemic corticosteroid therapy (7% vs 27%; P < 0.05). None of the children in the budesonide group, in contrast to 23% of those in the placebo group, required hospitalization (P < 0.05). The length of hospital stay (i.e. time taken to recover from acute asthma) was significantly shorter in the intervention group (3.2 +/- 2.5 h) than in the placebo group (7.8 +/- 11.3 h; P < 0.01).. Aerosolized budesonide therapy (with MDI and spacer) together with nebulized salbutamol early in the emergency room treatment of acute moderate exacerbations of asthma helped in early recovery and decreased the need for hospitalization. It may be worthwhile calculating this regimen for home-based early treatment of acute exacerbations.

Topics: Acute Disease; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Heart Rate; Humans; Male; Oximetry; Severity of Illness Index; Treatment Outcome

The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting beta2-agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life. Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 microg budesonide, patients were randomized to either 200 microg (Bud200) or 800 microg budesonide (Bud800) in combination with either 24 microg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months. During the run-in, there was an improvement in AQLQ score (changes (delta) in overall score approximately 0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (delta=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51). Improvements in quality of life, which were greatest in the 800 microg budesonide plus 24 microg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience.

Topics: Adrenergic beta-Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Outcome Assessment, Health Care; Quality of Life; Surveys and Questionnaires; Time Factors

A total of 198 children aged 3 to 15 years inhaled a single dose of 200 micrograms budesonide from a Nebuhaler pressurized metered dose inhaler (pMDI) and a Turbuhaler dry powder inhaler in a randomized crossover study. The budesonide dose delivered to a patient was assessed by measuring the amount of drug deposited on a filter inserted between the inhaler outlet and the patient's mouth. The dose of budesonide deposited on the filter and the estimated dose of particles with a mass median aerodynamic diameter (MMAD) of 5 microns or less after inhalation from the Turbuhaler were both approximately twice the values inhaled from the pMDI Nebuhaler in children less than 5 years of age (P < 0.01). The variation in the dose delivered to the patient was similar for the two inhalers in children over 5 years old. In 3- to 4-year-old children, dose delivery to the patient was higher and/or more consistent from the pMDI Nebuhaler than from the Turbuhaler. Filter dose after Turbuhaler treatment varied significantly from peak inspiratory flow rate through the Turbuhaler (PIFTbh) (P < 0.01). The percentage of children producing a PIFTbh greater than 50 L/min decreased with age (89%, 45%, and 14% in 5-, 4-, and 3-year-old children, respectively). It is concluded that drug delivery to a child with asthma varies with age and inhalation device. Further studies are needed to assess the clinical importance of this finding.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Delivery Systems; Equipment Design; Female; Humans; Male; Nebulizers and Vaporizers; Particle Size; Pressure; Reference Values; Sensitivity and Specificity

Limited cooperation and low tidal volumes in infants make aerosol therapy difficult. We measured the amount of drug delivered from two baby spacer devices especially developed for use in infants. Designed as a randomized crossover study, aerolized budesonide from a pressurized metered dose inhaler (pMDI) was collected in the inspiratory filter interposed between the face mask and the spacer in 13 infants aged from 2 to 19 months old. The study was performed in connection with pulmonary function testing with a plethysmograph, and the children were sedated with cloral hydrate. Two small-volume baby spacer devices were used: a Babyhaler spacer (GlaxoWellcome, Hertfordshire, UK) made of polycarbonate with a volume of 350 mL and a built-in dead space of 40 mL and a NebuChamber spacer (AstraZeneca, Lund, Sweden) made of stainless steel with a volume of 250 mL and no dead space. Budesonide delivery from the NebuChamber was significantly higher than from the Babyhaler: 38.2% (range, 28.3%-47.5%) of the nominal dose versus 12% (range, 3.3%-21.25%) of the nominal dose of 400 micrograms of budesonide (P = 0.002). The inhaled mass of budesonide from the Babyhaler correlated significantly with skin surface area (r = 0.68, P = 0.018), weight (r = 0.66, P = 0.019), height (r = 0.69; P = 0.017), tidal volume (r = 0.82; P = 0.004), and minute volume (r = 0.67; P = 0.019). No correlations were found between these variables and the inhaled mass of budesonide from the NebuChamber. The results indicate that the design of the NebuChamber spacer affords stable drug delivery in infants and that a large variability in the inhaled mass of drug may be found when infants are inhaling from different baby spacers.

Topics: Administration, Inhalation; Anthropometry; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Equipment Design; Female; Humans; Infant; Infant, Newborn; Male; Nebulizers and Vaporizers; Plethysmography; Respiratory Function Tests; Sensitivity and Specificity; Statistics, Nonparametric

The aim of our study was to assess the effects of long-term treatment with inhaled budesonide (BUD) on total body bone mineral density (BMD), total body bone mineral capacity (BMC), total bone calcium (TBC), and body composition in children with asthma. Dual energy X-ray absorptiometry (DEXA scan) was performed in 157 asthmatic children treated with inhaled BUD at a mean daily dose of 504 microg (range, 189 to 1,322 microg) for 3 to 6 yr (mean, 4.5 yr). Measurements were compared with those of 111 age-matched children also suffering from asthma but who had never been treated with exogenous corticosteroids for more than 14 d (control group). There were no statistically significant differences between the two groups in BMD (BUD = 0.915 g/cm2, controls = 0.917 g/cm2), BMC (BUD = 1,378 g, controls = 1,367 g), TBC (BUD = 524 g, controls = 519 g), or body composition (lean body weight = 27,600 g [BUD] and 26,923 g [control], % body fat = 20.1% [BUD] and 20.3% [control]). Furthermore, there was no correlation between any of these parameters and duration of treatment, accumulated or current dose of budesonide. Three to six years of treatment with inhaled budesonide at an average daily dose of 504 microg has no adverse effect on total BMD, total BMC, TBC, or body composition in children with chronic asthma.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Asthma; Body Composition; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Calcium; Child; Cross-Sectional Studies; Drug Monitoring; Female; Humans; Male; Prospective Studies; Time Factors

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Case-Control Studies; Chemokine CCL3; Chemokine CCL4; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferon-gamma; Interleukin-10; Macrophage Inflammatory Proteins; Macrophages, Alveolar; Male

The aim of this study was to evaluate the steady-state effects of once-daily inhaled fluticasone propionate (FP) and budesonide (BUD) on adrenocortical activity in asthmatic patients.. Ten asthmatic patients with a mean age of 31.2 years, a mean forced expiratory volume in 1 s (FEV1) of 91% predicted and a forced mid-expiratory flow (FEF25-75) of 62.3% predicted were studied in a single-blind randomised crossover design comparing placebo (PL), FP (375 microg per day and 750 microg per day) and BUD (400 microg per day and 800 microg per day) all given once daily for 4 days at each dose via a pressurised metered dose inhaler (pMDI) at 0800 hours. After 4 days of treatment, plasma cortisol was measured at 0800 hours (24 h after the last dose) and a 10-h overnight urine collection was taken, 14 h after the last dose (2200-0800 hours) for analysis of cortisol and creatinine excretion.. Plasma cortisol levels (nmol.l(-1), as geometric mean) at 0800 hours demonstrated a significant difference between the highest doses of FP and BUD (424.1 vs 510.3 nmol.l(-1), respectively) but not between the low doses (506.8 vs 514.9 nmol.l(-1); PL 532.2 nmol.l(-1)). For the highest dose FP (750 microg) this equated to 20% suppression of 0800 hours plasma cortisol. Likewise, for overnight urinary cortisol output (nmol.10 h(-1) as geometric mean), there was a significant difference at the high doses of FP and BUD (25.5 vs 38.2 nmol.10 h(-1)), but not at the low doses 31.3 vs 34.8 nmol.10 h(-1); PL 32.0 nmol.10 h(-1). For the overnight urinary cortisol/creatinine ratio (nmol.mmol(-1), as geometric mean) there was a similar trend; 4.5 vs 6.1 nmol.mmol(-1) for high dose and 5.6 vs 6.3 nmol.mmol(-1) for low dose; PL 5.9 nmol.mmol(-1).. Repeated doses of FP 750 microg once daily caused greater adrenal suppression than BUD 800 microg once daily, when comparing effects on plasma cortisol levels at 0800 hours, 24 h after the last dose, as well as effects on overnight urinary cortisol output. Neither FP 375 microg once daily nor BUD 400 microg once daily produced detectable adrenal suppression.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocortisone; Male; Single-Blind Method

There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.

Topics: Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Belgium; Bone Density; Bronchodilator Agents; Budesonide; Calcium; Cross-Over Studies; Double-Blind Method; Female; Femur Neck; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hydroxyproline; Male; Middle Aged; Osteocalcin; Peak Expiratory Flow Rate; Safety; Salmeterol Xinafoate; Spine

The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients. A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment. In actual fact, the apparent order of effect was: 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device. The adverse effects reported appeared to be related to the dose rather than delivery device. Accordingly, the effect was related to total mass output, rather than to the small particle fraction of the budesonide aerosol. These results attest to the efficiency of jet-nebulized budesonide suspension, and indicate nebulized budesonide to be equipotent to standard budesonide therapy delivered by pMDI with Nebuhaler, provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers

The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open-label, cross-over study of adult asthmatics. Patients received, in random order, either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD, or vice versa, with an intervening 4 week 'wash-out' period between treatments. Thirty patients completed the study, of whom 24 were evaluable. In terms of the primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l min-1) from baseline to the fourth week of each treatment period, FP was more effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)] and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger reductions in diurnal variation were observed during FP treatment [mean treatment difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)]. There was no significant difference between the treatments for the proportion of symptom-free 24 h periods. Of those expressing a preference, significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than nebulized budesonide. In addition, cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Costs and Cost Analysis; Cross-Over Studies; Drug Delivery Systems; Fluticasone; Humans; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate

To compare the clinical effect of nebulized budesonide with placebo in acute pediatric asthma.. A randomized, controlled, double-blind trial with parallel design was used in the ED of a tertiary care children's hospital. Children aged 6 months to 18 years with a moderate to severe exacerbation of asthma [Pulmonary Index Score (PIS) > or = 5 or < or = 11 after a salbutamol nebulization of 0.15 mg/kg] were eligible. All patients received prednisone 1 mg/kg orally and nebulized salbutamol (0.15 mg/kg) every 30 minutes for 3 doses and then every hour for 4 hours. The intervention was 2 mg (4 mL) of nebulized budesonide or 4 mL of nebulized normal saline.. Baseline characteristics were comparable in the budesonide group (n = 24) and in the placebo group (n = 20). There were no significant differences in the primary outcome measure (PIS) between the 2 groups. However, the PIS at 1 hour had a tendency to be lower in the budesonide group (median = 5) as compared with the placebo group (median = 6; p = 0.07). Survival analysis of release/discharge from the ED/hospital showed a more rapid rate in the budesonide group as compared with the placebo group (p = 0.02). No adverse effects were seen.. Although these preliminary results suggest that nebulized budesonide may be an effective adjunct to oral prednisone in the management of moderate to severe asthma exacerbations, a larger trial will be required before the widespread use of inhaled budesonide in acute asthma can be advocated.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Emergencies; Female; Hospitalization; Humans; Infant; Male; Nebulizers and Vaporizers; Prednisone; Respiratory Function Tests

As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects.. This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma.. Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin.. After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo).. In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.

Topics: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Cosyntropin; Double-Blind Method; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisone

To investigate growth and markers of collagen and bone metabolism in prepubertal children with asthma.. We measured growth velocity over 12 months and markers of collagen types I and III synthesis (PINP, PICP, PIIINP), collagen type I degradation (ICTP), and bone metabolism (bone-specific alkaline phosphatase and osteocalcin) on one occasion in 56 prepubertal children with stable asthma, 39 of whom were treated with inhaled budesonide or beclomethasone. Collagen data were compared with normal control values.. Children treated with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with control subjects (p = 0.038, p = 0.045), although PICP was increased (p = 0.05). Carboxyterminal telopeptide of type I collagen was reduced in patients treated with inhaled steroids (p < 0.0005) compared with nonsteroid-treated patients. Serum osteocalcin but not bone-specific alkaline phosphatase was significantly reduced in children treated with inhaled steroids (p < 0.02). Significant correlation was observed between PIIINP and ICTP and growth velocity.. Collagen turnover is reduced in children with asthma receiving long-term inhaled steroid treatment. Markers of collagen synthesis provide a more accurate reflection of growth disturbance than osteocalcin and bone-specific alkaline phosphatase.

Topics: Administration, Inhalation; Alkaline Phosphatase; Asthma; Beclomethasone; Bone and Bones; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Collagen; Female; Glucocorticoids; Growth; Humans; Male; Osteocalcin

Airway inflammation is a hallmark of asthma, therefore current treatment recommendations include the use of inhaled glucocorticosteroids (GCS). However, there is little evidence that the effects of inhaled GCS are dose dependent.. The objective of this study was to assess the efficacy and safety of a second-generation GCS, budesonide, delivered by Turbuhaler, in adults with chronic asthma.. In a 12-week, randomized, double-blind, multicenter, parallel-group study, 473 subjects 18 to 70 years of age received either placebo or budesonide (200, 400, 800, or 1600 microg total daily dose) administered twice daily. Primary efficacy end points were mean change from baseline for FEV1 and morning peak expiratory flow. Safety was assessed by reported adverse events and by a cosyntropin-stimulation test.. The mean baseline FEV1 was 63% to 66% of predicted normal value between groups. All doses of budesonide were more effective than placebo (p < 0.001). The mean changes in morning peak expiratory flow were 12, 22, 27, and 30 L/min in the 200, 400, 800, and 1600 microg budesonide total daily dose groups, respectively, and -27 L/min for the placebo group. A statistically significant dose-response effect for the mean change from baseline over the 12-week study was seen for both morning peak expiratory flow and FEV1. Budesonide-treated subjects also demonstrated significant reduction in asthma symptoms and bronchodilator use compared with placebo. There were no clinically significant differences in treatment-related adverse experiences among groups.. Budesonide administered by Turbuhaler exhibited a dose response and was effective at low doses. It was well tolerated and significantly more effective than placebo.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers

There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose.. In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test.. The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B (p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level.. The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Budesonide; Child, Preschool; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Male; Recurrence; Respiratory Sounds; Suspensions

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bone Density; Budesonide; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Pilot Projects

The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Rhinitis, Allergic, Perennial

Electrostatic charge in plastic spacer devices has been shown in vitro to reduce delivery of asthma medications intended for inhalation, but the effect of static charge on in vivo drug deposition is unknown. A six-way randomized crossover study was conducted in 10 mild asthmatic patients. Two plastic spacers (Nebuhaler and Volumatic) and one metal spacer (Nebuchamber) were tested. The spacers were used either "primed" or "unprimed". Priming was performed by firing 20 doses of placebo aerosol into a new spacer, hence coating the inner surface with surfactant and minimizing static charge. Unprimed spacers were new and were not treated. Pressurized aerosol canisters delivering budesonide (200 microg Pulmicort) were radiolabelled with the radionuclide 99mTc and lung deposition was measured by gamma scintigraphy. The radiolabel was shown to be a valid marker for the drug substance prior to the clinical phase of the study. Priming significantly increased mean whole lung deposition following inhalation from plastic spacers (Nebuhaler primed 37.7% and unprimed 26.7%, p=0.01; Volumatic primed 32.0% and unprimed 22.1%, p=0.02). Priming had no effect on the mean whole lung deposition following inhalation from the Nebuchamber (primed 33.5% and unprimed 32.9%). Lung deposition in vivo from plastic spacer devices will vary according to the electrostatic charge on the spacer walls. Priming reduces retention of drug on plastic spacer devices and increases lung deposition. Metal spacers are not susceptible to static charge, which should result in more predictable lung deposition.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Female; Glucocorticoids; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Plastics; Radionuclide Imaging; Static Electricity; Steel; Technetium

To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma.. Double-blind, randomized, and placebo-controlled study, with parallel groups.. Multicenter study in outpatient setting.. Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg.. After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals.. Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects.. Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Prednisone; Respiratory Function Tests

Regular inhaled beta 2 agonist therapy is associated with loss of bronchoprotection to indirect bronchial provocation challenges such as allergen or adenosine monophosphate (AMP), while directly acting challenge is less affected, implying preferential mast cell tolerance. Glucocorticosteroids may reverse such beta 2 adrenoreceptor tolerance and upregulate mast cell beta 2 adrenoceptor function.. The effect of single high dose glucocorticosteroids on terbutaline induced loss of bronchoprotection was studied in a placebo controlled, double blind, cross-over study. Fifteen asthmatic subjects who were not taking inhaled glucocorticosteroids underwent two 10-day treatment periods with terbutaline (500 micrograms four times daily via Turbohaler), each followed by a single dose of inhaled budesonide (800 micrograms via Turbohaler) or identical placebo.. Regular treatment with terbutaline resulted in significant loss of bronchoprotection to AMP (mean difference (95% CI) -1.7 (-3.0 to 0.4) doubling dilutions) but not to methacholine (mean difference -0.1 (-1.0 to 0.8) doubling dilutions). Single high dose budesonide increased the protective effect of terbutaline more to AMP than to methacholine challenge (+0.76 (0.3) doubling dilutions compared with +0.13 (0.4) doubling dilutions, respectively). The mean (SE) difference between budesonide and placebo for methacholine challenge was 0.08 (0.14) whereas that for AMP was 0.075 (0.15); p = NS. The difference in PC20 was not statistically significant when compared with placebo for either challenge agent.. Inhaled glucocorticosteroids in a single dose had no significant effect in restoring terbutaline induced loss of bronchoprotection, implying that mast cell beta 2 adrenoceptor sensitivity is not restored by a single dose of an inhaled glucocorticosteroid in asthma.

Topics: Adenosine Monophosphate; Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Glucocorticoids; Humans; Lung; Male; Mast Cells; Methacholine Chloride; Middle Aged; Muscle, Smooth; Terbutaline

To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma.. In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value.. Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups.. Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders

New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive patients with asthma. The study had a 13-wk randomized, double-blind, parallel design: 1-mo treatment with 400 microg budesonide twice a day, or 100 microg budesonide twice a day by dry powder inhaler, and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients. Forty patients started with 400 microg budesonide twice daily, 44 with 100 microg budesonide twice daily. Mean age was 32 yr, baseline FEV1 value 84% predicted, reversibility 9% from baseline, and mean bronchodilator use 1.6 inhalations/d in the run-in period. After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow (PEF) increased 27 L/min (SD 50), and 38 L/ min (SD 53), respectively (p = 0.30); mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5. These effects were maintained in the 2 mo follow-up. This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Primary Health Care; Respiratory Function Tests; Spirometry; Treatment Outcome

The effectiveness of inhaled corticosteroids in the control of daytime symptoms in asthma is well established, but the specific use against nocturnal asthma has not been systematically studied in Asian patients. This study examined the effect of treatment with inhaled budesonide on the nocturnal variation in measurements of airway calibre, bronchial hyperresponsiveness to inhaled histamine and circulating neutrophil chemotactic activity in Asian patients with nocturnal asthma. Thirty patients, with nocturnal asthma, were randomized into a 2-month, double-blind, parallel group study. Twice as many subjects were allocated to the group who received two consecutive months of inhaled budesonide 1600 microg daily as to the group who received placebo followed by budesonide. Spirometry, lung mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor (NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4 weeks apart before and after either placebo or budesonide. The combined measurements for the two groups at 04.00 h before and after treatment with budesonide were: forced expiratory volume in 1 s (FEV1) mean (SEM) litres 1.34 (0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32) before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)(-1) 0.39 (0.07) before, 1.16 (0.17) after; PD20 microg geometric mean 1.16 before, 44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and intermediate term high dose inhaled budesonide is an effective specific treatment for nocturnal asthma in Asian patients, resulting in marked improvements in symptoms and in lung mechanics, and reductions in the diurnal variations in bronchial hyperresponsiveness, before any change could be demonstrated in a circulating marker of airway inflammation.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Chemotactic Factors; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neutrophils; Respiratory Function Tests; Singapore

Inhaled steroid therapy is the most important treatment in the management of chronic asthma and currently twice-daily administration is recommended in mild to moderate asthma. Compliance is often a problem in asymptomatic patients and may lead to reduced disease control. Our aim was to investigate whether budesonide 0.2 mg once daily administered via the Turbuhaler is as effective as 0.1 mg twice daily. A randomized, double-blind, parallel group study was carried out in which 76 adult patients with mild to moderate asthma (FEV1 86% of predicted) were allocated to budesonide once or twice daily. After a run-in period of 2 weeks on present inhaled steroid treatment (0.2-0.5 mg day-1) there was an 8 week treatment period, followed by a washout period in which patients received no steroid for 4 weeks unless a drop in morning peak flow of at least 20% occurred or the use of beta 2-agonists increased by 50%. Both treatment groups improved minimally in peak flow (1.7 and 4.31 min-1 in the once-daily and twice-daily groups respectively) but the differences between the two groups were not significant. Testing the reverse hypothesis revealed clinical equivalence. The 90% confidence interval of the difference in the change of peak flow from run-in was between +30 and -30 l min-1, the limits deemed to be clinically relevant. There were no differences in symptom scores, beta 2-agonist use or spirometry measurements between the two groups. In the washout period there was a significant deterioration in peak flow and symptoms. This study shows that 0.2 mg budesonide given once a day is as affective as 0.1 mg given twice daily in patients with mild to moderate asthma.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

The effects of budesonide, nedocromil sodium and salmeterol on bronchial hyperresponsiveness were determined over a period of 3 weeks.. Forty-three asymptomatic children (22 male, 21 female, aged 7-17 years) with mild-to-moderate asthma were evaluated. The study was placebo-controlled and double-blind. At the beginning the forced expiratory volume in 1 second (FEV1) was measured and a methacholine challenge was performed to determine PC20 (provocative concentration of inhaled methacholine required to reduce FEV1 by 20%). The patients in group I (n = 12), group II (n = 10), group III (n = 11), and group IV (n = 10) inhaled 200 micrograms of budesonide, 2 mg of nedocromil sodium, 25 micrograms of salmeterol and a placebo, respectively, twice a day over the period of 3 weeks. Then the methacholine PC20 values of all patients were measured again and the results were compared statistically with their previous values.. The statistical data revealed that the methacholine doses in PC20 before and after treatment were different in group I (P < 0.01). However, these differences were not statistically significant in the other groups (P > 0.05).. The short term usage of budesonide decreases bronchial hyperresponsiveness, but nedocromil sodium and salmeterol in the given dises do not affect bronchial hyperresponsiveness.

Topics: Adolescent; Albuterol; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Humans; Male; Matched-Pair Analysis; Nedocromil; Salmeterol Xinafoate; Statistics, Nonparametric

Peroxynitrite is a potent oxidant formed by the rapid reaction of the free radicals nitric oxide (NO) and superoxide. It causes airway hyperresponsiveness and airway epithelial damage, enhances inflammatory cell recruitment, and inhibits pulmonary surfactant. Asthma is characterized by increased airway hyperresponsiveness, airway epithelial shedding, and inflammation. We examined the production of peroxynitrite and the expression of inducible nitric oxide synthase (iNOS) in airways of asthmatic patients compared to normal control subjects. We also performed a double-blind, crossover randomized-order, placebo-controlled study on 10 asthmatic patients to study the effects of inhaled glucocorticoid treatment (Budesonide) on the formation of peroxynitrite and NO. Fiberoptic bronchial biopsies were examined by immunohistochemistry with antiserum to nitrotyrosine, a marker of protein nitration by peroxynitrite. We also examined the expression of iNOS by immunohistochemistry and in situ hybridization, and measured exhaled NO by chemiluminescence. We correlated the airway production of peroxynitrite with pulmonary functions and airway responsiveness. In airway passages of control subjects, there was weak or no nitrotyrosine immunoreactivity. In contrast, there was strong immunoreactivity for nitrotyrosine in the airway epithelium and inflammatory cells in the airways of persons with asthma. Budesonide treatment resulted in a significant reduction in nitrotyrosine immunoreactivity. Expression of iNOS was evident in the airway pithelium of controls and asthmatic patients, but was significantly more abundant in asthmatic patients. The presence of nitrotyrosine in the airway epithelium (r=-0.841, P<0.0001; r=-0.771, P=0.0004) and inflammatory cells (r=-0.727, P=0014; r=-0.681, P=0.004) correlated inversely with methacholine PC20 and forced expiratory volume in 1 s, respectively. Asthma is associated with increased peroxynitrite formation in the airways, which is reduced after Budesonide treatment. The potent oxidant peroxynitrite may contribute to airway obstruction and hyperresponsiveness and epithelial damage in asthma.

Topics: Administration, Inhalation; Adult; Asthma; Bronchi; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Enzyme Induction; Female; Glucocorticoids; Humans; Male; Nitrates; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidants

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from suppressed bone formation may therefore contribute to glucocorticoid-associated bone loss in asthma. Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG. Although the effects of high-dose IG on BMD are associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Beclomethasone; Biomarkers; Bone Density; Budesonide; Dehydroepiandrosterone Sulfate; Female; Femur; Glucocorticoids; Humans; Hydrocortisone; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Ribs

We investigated the 1-year outcome of children hospitalized for wheezing, paying special attention to the effect of early anti-inflammatory therapy. In addition, we identified risk factors for recurrent wheezing and asthma. Eighty-eight children under 2 years old treated in the hospital for wheezing were followed for 1 year. Nebulized anti-inflammatory therapy was given for 16 weeks: 31 patients received budesonide, 29 patients cromolyn sodium, and 28 control patients received no therapy. The number of subsequent physician-diagnosed wheezing episodes was recorded. Four months of anti-inflammatory therapy did not significantly decrease the occurrence of asthma 1 year later; 45% of patients in the cromolyn group, 42% in the budesonide group, and 61% in the control group had asthma, defined as at least two bronchial obstruction episodes during the 1-year period after the original hospitalization for wheezing. An age over 12 months at the time of the initial bronchial obstructing episode [P=0.009, risk ratio (RR)=5.4, 95% confidence interval (CI)=1.53-19.31], failure to identify a viral cause (P=0.0003, RR=12.0, CI=3.16-45.40), history of wheezing (P=0.02, RR=14.6, CI=1.59-132.10), the presence of atopy (P=0.01, RR=5.3, CI=1.47-19.21), a family history of atopy (P=0.03, RR=3.6, CI =1.15-11.12), and serum eosinophil cationic protein (ECP) > or = 16 microg/L (P=0.005) were significant risk factors for asthma. We conclude that early anti-inflammatory therapy for 4 months does not significantly decrease the occurrence of asthma during the period of 1 year following hospitalization for the original episode of wheezing. Young children requiring hospital admission for wheezing during a respiratory tract infection are at increased risk of having subsequent asthma if they have wheezed previously, if they have atopy or a family history of atopy, if they have elevated serum ECP, if they are over 12 months of age at the original bronchial obstructive episode, and especially when viral studies are negative.

Topics: Administration, Inhalation; Administration, Oral; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchi; Budesonide; Chi-Square Distribution; Child, Preschool; Cromolyn Sodium; Dermatitis, Atopic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypersensitivity; Infant; Infant, Newborn; Logistic Models; Male; Prospective Studies; Recurrence; Respiratory Sounds; Risk Factors; Theophylline; Time Factors

Standardization of conditions for peak expiratory flow (PEF) monitoring is much more difficult in practice than for laboratory spirometry. Patients are usually asked to record PEF before medication. The aim of this study was to determine the effect of prior bronchodilator use on PEF outcome measures in a clinical trial. Electronic PEF records from 43 subjects with poorly controlled asthma were examined to determine the frequency with which beta2-agonist was inhaled <4 h before PEF measurement, as such PEF are potentially "postbronchodilator". The effect of inclusion of such PEF values on improvement in PEF outcome measures after 8 weeks of inhaled budesonide was calculated. Subjects were asked to record PEF before medication. During run-in, the median frequency of postbronchodilator PEF was 29%, falling to 0% after 8 weeks of budesonide. Inclusion of postbronchodilator PEF led to an overestimation of average morning, evening and daily PEF during run-in (p<0.001). Improvement in these indices with treatment was, therefore, underestimated. Minimum morning PEF expressed as per cent personal best was unaffected. Subjects may not be able to withhold beta2-agonist for 4 h before every peak flow reading. This may change as the level of asthma control changes, leading to a systematic bias in clinical trial end-points or inaccuracy in individual treatment decisions. Simple changes to peak expiratory flow instructions and analysis are proposed.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Bias; Bronchodilator Agents; Budesonide; Female; Humans; Male; Peak Expiratory Flow Rate; Spirometry; Time Factors

We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Bronchial Provocation Tests; Bronchitis; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Disease Progression; Eosinophil Granule Proteins; Eosinophils; Female; Glucocorticoids; Humans; Inflammation Mediators; Leukocyte Count; Male; Methacholine Chloride; Middle Aged; Peak Expiratory Flow Rate; Placebos; Ribonucleases; Salmeterol Xinafoate; Spirometry; Sputum

To study the impact of both audiovisual information and nurse-training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler.. A single-blind, randomized, parallel-group trial studied 72 children aged 3-5 y. All children and their parents were shown an instructional video and given written instruction. After this, peak inspiratory flow (PIF1) through Turbuhaler was measured. Children in group A (n = 36) then received individual training by a nurse while those in Group B (n = 36) did not and PIF2 was measured. Afterwards, Group B received similar individual training while Group A received no additional training, and PIF3 was measured. Group A was given a placebo Turbuhaler and encouraged to practice at home. Two weeks later, both groups returned to the clinic where PIF4 was measured.. The number of children who were able to correctly perform PIF1, PIF2 and PIF4 in Group A was 27, 34 and 36, respectively. The corresponding numbers for Group B were 30, 29, and 29. No effect of training was seen in 3-y-old children. Individual training by a nurse was associated with a statistically significant increase in PIF2 (10 l/min; p = 0.014). Moreover, 2 weeks of home training was associated with an additional increase in PIF of 8 l/min compared with Group B (p < 0.015). After individual instruction and home training, mean PIF in children aged 4 and 5 was 56 (42-72) and 55 (41-66) l/min, respectively.. After individual instruction and training at home, the vast majority of children aged 4 and 5 y can use Turbuhaler correctly. Audiovisual information and individual instruction is not sufficient in the majority of these children. Few 3-y-old children can learn the correct use of Turbuhaler.

Topics: Analysis of Variance; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Female; Humans; Male; Nebulizers and Vaporizers; Patient Education as Topic; Peak Expiratory Flow Rate; Prospective Studies; Single-Blind Method

One hundred and sixty seven children on 0-200 microgram/day of inhaled steroid with asthma symptoms and sub-optimal peak flow values (less than 90% of that predicted for their height) were randomly allocated either 400 microgram once daily (nocte with placebo o.m.) or 200 mircrogram twice daily of budesonide Turbohaler for 8 weeks. Bronchdilator usage and symptoms were reduced in both groups at 4 and 8 weeks compared with baseline. There was a significant increase within both groups in morning and evening PEF after 4 and 8 weeks. The increase in evening PEF after 8 weeks was greater in the once-daily group than in the twice-daily group but there were no other significant differences between the groups (morning: +24.6 l/min vs 15.2 l/min, p = 0.059; evening: + 19.7 l/min vs +8.31 l/min; p = 0.013). Budesonide Turbohaler 400 microgram once daily is therefore as effective as 200 microgram twice daily in achieving asthma control in children.

Topics: Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Treatment Outcome; Vital Capacity

A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response.. Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC20 was measured before and after 6 days of treatment, and allergen PC15 was measured after 7 days of treatment.. The allergen PC15 (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics.. A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hypersensitivity, Immediate; Male; Methacholine Chloride; Middle Aged; Placebos

Because nebulized budesonide may be used as an alternative to maintenance oral prednisolone in the treatment of severe chronic asthma, it is important to compare these two drugs to determine their relative systemic bioactivity profiles in terms of effects on adrenal, bone, and hematologic markers.. Twelve asthmatic patients (mean age; 34.7 years; mean FEV1; 88.3% predicted; mean forced expiratory flow between 25% and 75% of FVC, 54.8% predicted) were studied in a double-blind, double-dummy, randomized crossover design to compare placebo, low, medium, and high doses of nebulized budesonide given bid (1, 2, and 4 mg/d, respectively), and oral prednisolone given qd (5, 10, and 20 mg/d). All treatments and both placebos were given for 4 days at each dose level with a 7-day washout period between each treatment block with budesonide or prednisolone. All measurements were made at 8 AM after the last dose of each dose increment for plasma cortisol, serum osteocalcin, and blood eosinophil count.. Regression analysis showed significant dose-related suppression with prednisolone for 8 AM plasma cortisol (p<0.0001), osteocalcin (p<0.05), and blood eosinophil count (p<0.0005), but not with budesonide. Compared with placebo, there were significant differences only with prednisolone, at the medium- and high-dose levels for all three markers.. For all three systemic bioactivity markers (8 AM plasma cortisol, serum osteocalcin, and blood eosinophils), there was significant dose-related suppression with prednisolone but not with budesonide. Further long-term studies are required in more severe asthmatics in order to evaluate the therapeutic index.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Asthma; Biomarkers; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Follow-Up Studies; Humans; Hydrocortisone; Leukocyte Count; Male; Nebulizers and Vaporizers; Osteocalcin; Prednisolone; Respiratory Function Tests; Treatment Outcome

Topics: Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Bone Remodeling; Budesonide; Child; Female; Humans; Male; Osteocalcin; Prednisone; Time Factors

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogenous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 microg budesonide was given once in the morning, in the other 400 microg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 microg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P = 0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P = 0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Bone and Bones; Budesonide; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Osteocalcin; Radioimmunoassay; Statistics as Topic

Electronic spirometers offer the prospect of paperless home monitoring, but data quality is not automatically better than from conventional monitoring. The aim of this study was to determine the extent to which the quality and processing of self-recorded spirometric data from patients with asthma complied with international guidelines for spirometry. Data were from 33 subjects with poorly controlled asthma who had completed the first 9 weeks of a clinical budesonide trial. MicroMedical DiaryCard electronic spirometers were used to record three spirometric manoeuvres in twice-daily sessions. Confounding events were recorded in a paper diary. Within-session reproducibility was calculated for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) during the first week of run-in and week 9 of budesonide treatment. Geometric means of within-session reproducibility (mean difference between highest and second-highest value from each session over a one-week period) for FEV1, FVC and PEF were 76 mL, 116 mL and 18 L x min(-1), respectively, during run-in. Times of spirometric sessions varied widely, with some overlap between morning and evening session times. Manoeuvre-induced falls in PEF and FEV1 occurred only as often as expected by chance. Nonasthma events including equipment faults and painful conditions caused changes in spirometric results. Home spirometric monitoring can be carried out with excellent reproducibility in patients with asthma. However, quality-control issues are complex and an accompanying paper diary remains essential.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Electronics, Medical; Female; Home Nursing; Humans; Male; Middle Aged; Monitoring, Physiologic; Peak Expiratory Flow Rate; Reproducibility of Results; Self Care; Sensitivity and Specificity; Spirometry

Budesonide (BUD) has recently been licensed for treatment of asthma in the United States, whereas triamcinolone acetonide (TAA) has been used for many years.. We sought to evaluate the dose-response effect of inhaled BUD and TAA in terms of adrenal, bone, and blood markers.. Twelve asthmatic subjects (mean age, 32 years; mean FEV1, 91% of predicted value) were studied in a randomized design comparing 3 days of treatment with placebo and low (200 micrograms twice daily), medium (400 micrograms twice daily), and high (800 micrograms twice daily) doses of BUD (Pulmicort Turbuhaler, 100 micrograms) and TAA (Azmacort integrated actuator/spacer, 100 micrograms) with a 7-day period at crossover, when patients received their usual inhaled corticosteroid therapy. Measurements were made at 8 am for serum cortisol, osteocalcin, and blood eosinophils. Measurements were also made for overnight urinary cortisol/creatinine excretion.. For all measurements there were no significant differences between the 2 treatments at any dose level. Ratios between BUD and TAA (95% CI) at the highest dose levels were as follows: 8 am serum cortisol, 1.08-fold (0.63 to 1. 85); urinary cortisol, 1.09-fold (0.63 to 1.86); eosinophils, 0. 98-fold (0.69 to 1.38); and osteocalcin 1.05-fold (0.78 to 1.41). There was no evidence of a significant overall dose-response effect for any parameter of hypothalamo-pituitary-adrenocortical axis activity, with neither drug being significantly different from placebo at any dose. For the 3 dose levels of both drugs, total abnormal low values for 8 am serum cortisol (ie, <5.4 micrograms/dL [<150 nmol/L]) showed 2 of 36 for BUD and 2 of 36 for TAA. There was also no significant overall dose-response effect for eosinophils or osteocalcin, although both drugs were significantly (P <.05) different from placebo at the highest dose: eosinophils (x10(9)/L), placebo: 0.36, TAA: 0.24, and BUD: 0.23; and osteocalcin (nmol/L), placebo: 1.04, TAA: 0.73, and BUD: 0.77.. There were no significant differences in the systemic bioactivity profiles, in terms of adrenal, blood, and bone markers, between BUD administered by means of Turbuhaler and TAA administered by means of an integrated actuator/spacer in a dose range of 400 micrograms to 1600 micrograms/day. Both drugs exhibited a significant degree of detectable systemic bioactivity but only at the highest dose of 1600 micrograms/day for effects on eosinophil count and osteocalcin.

Topics: Adult; Asthma; Biological Availability; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Eosinophils; Female; Humans; Hypothalamo-Hypophyseal System; Male; Osteocalcin; Pituitary-Adrenal System; Placebos; Single-Blind Method; Triamcinolone Acetonide

Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers.. We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children.. This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients.. Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P

Topics: Administration, Inhalation; Asthma; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Time Factors

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Body Height; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Dwarfism; Female; Humans; Male; Survival Rate

Twice-daily administration of inhaled budesonide (400 micrograms) suppresses short-term growth in children with asthma.. To compare short-term growth and markers of collagen turnover during treatment with 800 micrograms of inhaled budesonide administered once daily in the morning and 400 micrograms administered twice daily.. Twenty-four children with asthma aged 5.6 to 12.5 years.. An outpatient secondary referral center.. A randomized, double-blind, crossover trial with 2 treatment periods of 4 weeks was conducted, and growth was assessed with a knemometer. The carboxy terminal propeptide of type I procollagen, the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen, the amino terminal propeptide of type III procollagen (PIIINP), and urinary pyridinoline and deoxypyridinoline were evaluated.. Mean lower leg growth rate (P = .04), PINP (P = .03), and PIIINP (P < .01) were suppressed during twice-daily administration of budesonide, 400 micrograms. Otherwise, no statistically significant differences were detected.. As compared with 400 micrograms of inhaled budesonide administered twice daily, 800 micrograms administered once daily in the morning has a sparing effect on short-term growth and collagen turnover.

Topics: Administration, Inhalation; Anthropometry; Anti-Inflammatory Agents; Asthma; Body Height; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Collagen; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV1) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 microg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV1 was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutaline Turbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV1 from baseline to day 7 was 17.3% in the budesonide Turbuhaler group and 17.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Medical Records; Middle Aged; Prednisolone; Spirometry

Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchial Provocation Tests; Budesonide; Cross-Over Studies; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Leukocyte Count; Male; Ribonucleases; Sputum; Tumor Necrosis Factor-alpha

The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Exercise; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Pulmonary Ventilation

This double-blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort Turbohaler) at a loading dose (LD) (400 micrograms b.d.) for 6 weeks, followed by step down to 400 micrograms nocte for 12 weeks, compared with a static dose (SD) (400 micrograms nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 l/min), who demonstrated > or = 15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 l/min, both groups), symptom score (LD -0.57, SD -0.49, on a scale of 0-3), sleep disturbance (LD -1.21 nights/week, SD -1.06 nights/week) and beta 2-agonist use (LD -1.36 puffs/day, SD -1.06 puffs/day), within both groups (each p = 0.0001). At 18 weeks, 82% (LD) and 84% (SD) of patients benefited from no nocturnal wakening in the previous 7 days. Overall, at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LD +36 l/min, SD +26 l/min) and beta 2-agonist use (LD -1.10 puffs/day, SD -0.94 puffs/day) were greater in the loading dose than in the static dose group (each p < 0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p < 0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 micrograms b.d.).

Topics: Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Thirty asthmatic patients were evaluated to assess the association of therapy with inhalatory corticosteroids and an educational program, EDUCASMA. Spirometric evaluation with Flow-Volume loop (MEDICAL GRAPHIC CPF-S), ambulatory FEP (mini WRIGHT meters) was performed. In regard of initial symptoms patients were qualified as moderate or severe. After two weeks of a screening period, they were randomized into 2 groups: a) beclomethasone; b) budesonide; respective doses in according to the initial status. During the study period (8 wks) they visited the medical Staff six or more times. In each visit the patients received clinical evaluation (i.e. clinical scoring), spirometry (i.e. FEV1), and FEP ambulatory revision. FEP x (mean), FEP delta, FEV1, and clinical scores values were matched at the start and at the end of the follow-up period. Non-parametric statistics were applied (Wilcoxon test) and significative changes were defined (p < 0.05).. 1) inhalatory corticosteroids therapy associated with a previous educational program could achieve early improvements of clinical scores; 2) in moderate asthma ambulatory FEP showed objective changes both in beclomethasone and budesonide treatments. It appears to indicate increasing changes very close to the clinical improvement; 3) the short period of our observation and the inflammatory condition of airways in severe asthma, could be explained as probable factors for the minor differences in the FEV1 evaluation; 4) no differences between budesonide and beclomethasone treatment were found.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Follow-Up Studies; Glucocorticoids; Health Education; Humans; Male; Middle Aged; Patient Education as Topic; Severity of Illness Index; Spirometry

The role of glucocorticoids in the treatment of chronic obstructive pulmonary disease (COPD) is controversial. We have previously described high numbers of neutrophils and high concentrations of the inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), and of the cell activation markers eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO), and human neutrophil lipocalin (HNL) in COPD patients as compared with controls, and have postulated that the cytokines TNF-alpha and IL-8 play a role in propagating the inflammatory response in COPD. We have now studied the effects of inhaled and oral glucocorticoids on these inflammatory indices in induced sputum. Initially, we studied the effect of a 2-wk course of inhaled budesonide (800 mg twice daily for 2 wk) in 13 patients with severe COPD (mean FDV1: 35% predicted). There was no clinical benefit in either lung function or symptom scores, and no significant change in the inflammatory indices as measured by total and differential cell counts and concentrations of TNF-alpha eosinophil activation markers ECP and EPO, and neutrophil activation markers MPO and HNL. Because the lack of anti-inflammatory effect might have been due to poor drug delivery as a result of severe airflow limitation, we undertook a study examining the antiinflammatory effect of oral prednisolone (30 mg daily for 2 wk) in patients with COPD and undertook the same measurements in 10 patients with atopic asthma. Sputum eosinophil numbers, ECP, and EPO were significantly reduced in the asthmatic patients but were not modified in COPD. This confirms the clinical impression that inhaled steroids have little antiinflammatory effect, at least in the short term in this group of patients, and suggests that the inflammatory process in COPD is resistant to the antiinflammatory effect of glucocorticoids.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Cytokines; Female; Glucocorticoids; Humans; Inflammation; Lung Diseases, Obstructive; Male; Middle Aged; Prednisolone; Pregnenediones; Respiratory Function Tests; Sputum

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Child; Circadian Rhythm; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Histamine H1 Antagonists; Humans; Ketotifen; Lung; Male; Methacholine Chloride; Peak Expiratory Flow Rate; Placebos; Pregnenediones

In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms. The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate (FP) and budesonide (B) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients.. Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second (FEV1) 89.0% predicted and mid forced expiratory flow (FEF25-75) 58.9% predicted, on 400 micrograms/day or less of inhaled corticosteroid, were studied in a double blind, placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms, 500 micrograms, and 1000 micrograms twice daily. Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing. Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours, 10 hours after the eighth dose.. The plasma cortisol levels (nmol/ l) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels: F500 333.8, B500 415.2 (95% CI 28.9 to 134.0); F1000 308.3, B1000 380.3 (95% CI 10.5 to 133.5); F2000 207.3, B2000 318.5 (95% CI 5.8 to 216.7); placebo 399.9. Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio (nmol/mmol) at all three dose levels: F500 3.12, B500 5.55 (95% CI 0.16 to 3.79); F1000 2.54, B1000 6.12 (95% CI 1.25 to 5.91); F2000 2.07, B2000 6.09 (95% CI 0.88 to 7.18); placebo 5.23.. With repeated dosing across a dose range of 250-1000 micrograms twice daily, fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol. It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients. Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency, prolonged receptor residency time, greater tissue retention, and a longer elimination half life.

Topics: Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Creatinine; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pregnenediones

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expiratory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteocalcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0007. analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p > or = 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Candidiasis, Oral; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Delivery Systems; Eosinophils; Female; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Osteocalcin; Pregnenediones; Respiratory Function Tests

Patients with asthma who have moderate to severe airway hyperresponsiveness often demonstrate progressive, unlimited airway narrowing in response to inhaled bronchoconstrictor stimuli, which is likely to be due to inflammatory changes within the airway wall. It is unknown whether regular therapy with inhaled steroids can limit this excessive response.. We investigated the effect of inhaled budesonide on the development of a plateau on the dose-response curve to methacholine in patients with asthma who did not show such a plateau before the study.. Thirty-one atopic patients with asthma (age, 19 to 31 years; FEV1 > 70% of predicted value; PC20 < 8 mg/ml) with documented absence of a maximal-response plateau to methacholine on two occasions during the run-in period, participated in a double-blind, placebo-controlled, parallel study. Standardized methacholine challenges were performed at -1, 0, 4, 8, and 12 weeks of treatment with inhaled budesonide, 800 microg two times a day, or corresponding placebo, and after a 2-week washout period. Airway response was measured by FEV1 (percent fall from baseline). A maximal-response plateau was considered if three or more consecutive data points fell within a 5% response range.. Thirty patients completed the study. There was a steady increase in the number of budesonide-treated patients exhibiting a maximal-response plateau on the dose-response curve from zero of 15 patients at run-in to nine of 14 patients at week 12, as compared with four of 16 patients in the placebo group (p = 0.03, chi square test). This was accompanied by a significant improvement in PC20 in the budesonide group as compared with the placebo group (p < 0.01 at week 12), whereas the changes in FEV1 were not significantly different between the groups (p = 0.77 at week 12).. Regular treatment with the inhaled corticosteroid budesonide limits maximal airway narrowing in response to methacholine by introducing a plateau on the dose-response curve in patients with asthma, who were initially characterized by the absence of a plateau. This indicates that inhaled steroids are likely to reduce the hazard of unlimited airway narrowing in asthma.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Pregnenediones

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos and Pari LL in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind, randomized, cross-over, dose titration study. After a 1-week run-in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos or a Pari LL nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2-week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2-week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period #1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos was twice as large as that delivered by the Pari LL: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos and 1.2 mg for Pari LL) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing.

Topics: Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Pregnenediones; Research Design; Single-Blind Method

In dermatological practice, allergy to topical corticosteroids used to treat eczema is a recognized and common event. The typical presentation is of an eczema which fails to improve or deteriorates with treatment. Topical corticosteroids are also used to treat mucosal disease. This study assesses allergy to inhaled corticosteroids in asthmatics. In the patient group selected, there was no evidence of relevant corticosteroid allergy.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Hypersensitivity; Female; Glucocorticoids; Humans; Immunoglobulin G; Intradermal Tests; Male; Methylprednisolone; Middle Aged; Pregnenediones

New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed.. This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma.. Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated.. No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period.. Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Aerosols; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Medical Records; Patient Compliance; Pregnenediones

Increased concentrations of exhaled nitric oxide (NO) occur in patients with asthma, and exhaled NO may be useful for assessing the effect of drug therapy on airway inflammation. Beta2-agonists have been proposed to have both proinflammatory and anti-inflammatory effects. We therefore assessed exhaled NO after beta2-agonists in asthmatic patients. Two randomized, double-blind, placebo-controlled studies were conducted. Firstly, exhaled NO was measured in 18 asthmatics (9 taking inhaled glucocorticosteroids (GCS)) before and after nebulized salbutamol (5 mg), or identical placebo (0.9% saline). Exhaled NO and forced expiratory volume in one second (FEV1) were measured at 15 min intervals for 1 h (Study 1). Secondly, the effect of 1 week of treatment with the long-acting beta2-agonist, salmeterol (50 microg b.i.d.), added to either budesonide (800 microg b.i.d.) or placebo, was studied in eight mild asthmatic subjects (Study 2). Exhaled NO was measured by a chemiluminescence analyser, adapted for on-line recording. In Study 1, exhaled NO showed no significant change at any time-point in patients not taking inhaled GCS. In asthmatics on inhaled GCS, exhaled NO increased compared to placebo at 15 and 30 min, but this did not reach statistical significance. In Study 2, treatment with salmeterol increased FEV1, but exhaled NO levels were not significantly changed, either after budesonide treatment (143+/-35 to 179+/-67 ppb), or after placebo (201+/-68 to 211+/-65 ppb). Our results confirm that single high dose salbutamol does not increase exhaled nitric oxide in asthmatics not taking inhaled glucocorticosteroids. Salbutamol may increase exhaled nitric oxide in asthmatics taking inhaled glucocorticosteroids. However, regular use of salmeterol resulted in no change in exhaled nitric oxide, either used alone or in combination with inhaled glucocorticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aerosols; Albuterol; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Nitric Oxide; Pregnenediones; Salmeterol Xinafoate; Time Factors

Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available. The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone propionate, budesonide and placebo were administered for 2 weeks in a randomized, double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged 6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder inhalers were used. Lower leg length was measured by knemometry twice a week during all three treatment periods, and 24 h cortisol excretion in the urine was measured at the end of each period. In the low-dose group, lower leg growth rate was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No significant difference (p=0.39) in lower leg growth rate was found between treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400 microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during treatment with budesonide, 400 microg x day(-1), was significantly lower than during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine during treatment with 200 microg x day(-1) fluticasone propionate was significantly reduced as compared with placebo (p=0.006), but not when compared with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1) was not significantly different from placebo. Fluticasone propionate and budesonide, both at 400 microg x day(-1), resulted in a significant reduction in cortisol excretion in the urine as compared with placebo (p=0.001). It is concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects.

Topics: Administration, Inhalation; Administration, Topical; Aerosols; Androstadienes; Anthropometry; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Growth; Humans; Hydrocortisone; Leg; Male; Pregnenediones

There is evidence that downregulation and desensitization of airway beta 2-adrenoceptors (beta 2-AR) develops after continuous exposure to long-acting beta 2-agonists such as formoterol and salmeterol. To investigate the facilitatory effects of acute administration of systemic corticosteroid on bronchodilator subsensitivity, as might occur in the setting of acute asthma, 12 subjects with moderately severe asthma, with a mean FEV1 of 66% predicted, of whom were all receiving inhaled corticosteriod, were randomized to receive either inhaled placebo (PL) or inhaled formoterol (FM) 24 micrograms twice daily for 4 wk in a double-blind crossover study. Subjects were also genotyped in terms of beta 2-Ar polymorphism at loci 16 and 27. A dose-response curve (DRC) and duration-time profile for FM (12 to 108 micrograms) was produced 1 h after administration of placebo tablets and after injection at 3 wk, and 1 h after administration of oral prednisolone, 50 mg, and intravenous hydrocortisone, 200 mg, at 4 wk. Comparisons between treatments were made with area-under-curve (AUC) measurements as the change from baseline. There was a significant rightward shift in the DRC after FM as opposed to placebo for delta FEV1 (as AUC, L.h): 2.51 versus 4.22 (95% CI: 0.54 to 2.89; p = 0.01) and delta FEF25-75 (as AUC, L x 10(3)): 11.30 versus 19.94 (95% CI: 2.12 to 15.12; p = 0.01). This was significantly reversed by steroid (S) for FEV1 (FM versus FM+5): 2.51 versus 3.57 (95% CI: 0.11 to 2.27; p = 0.03) and for FEF25-75: 11.30 versus 18.47 (95% CI: 2.52 to 11.70; p = 0.005). Lymphocyte beta 2-AR density (log Bmax; fmol/10(6) cells) showed significant upregulation 3 h after steroid (FM+5 versus FM): 0.34 versus 0.24 (95% CI: 0.02 to 0.18; p = 0.01). For heart-rate response (as AUC, beats), there was subsensitivity with FM versus PL: 2,700 versus 5,200 (95% CI: 40 to 5,000; p < 0.001), and this was reversed by steroid (FM+5 versus FM): 9,600 versus 2,700 (95% CI: 4,900 to 8,800; p < 0.001). This reversal by systemic corticosteroid appears to be generally independent of beta 2-AR polymorphism at loci 16 and 27. In conclusion, we have demonstrated that bronchodilator subsensitivity occurs after regular inhaled FM in asthmatic patients, and is rapidly reversed by systemic corticosteroid. Thus, in acute asthma, systemic corticosteroid should be administered a soon as possible, in order to restore normal airway beta 2-AR sensitivity, particularly in patients who are receiving regular

Topics: Adrenergic beta-Agonists; Adult; Area Under Curve; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Tolerance; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Pulmonary Ventilation

Inhaled corticosteroids are the most commonly used antiinflammatory agents for asthma. There is no simple way to compare objectively the relative potency of inhaled corticosteroids. The allergen-induced late asthmatic response (LAR) can be suppressed by a single dose of inhaled corticosteroid.. This study was undertaken to evaluate LAR as a model for the determination of the relative potency of single doses of inhaled corticosteroids.. We compared doses of 200 and 800 microg of a highly active inhaled corticosteroid (budesonide) with placebo and a marginally active investigational inhaled corticosteroid (D5159). Ten atopic patients with asthma completed a randomized, double-blind, double-dummy, multicenter, four-way, crossover trial. A standardized allergen challenge with the identical dose of allergen was performed 10 minutes after each of four blinded, single-dose treatments: 200 microg of budesonide, 800 microg of budesonide, 8 mg of D5159, and placebo, all administered from Turbuhaler. The LAR was recorded as the maximum percent fall in FEV1 between 4 and 7 hours, and the allergen-induced increase in methacholine airway responsiveness at 24 hours was recorded as the A log PC20 from the day before to the day after allergen challenge.. There were no significant differences in the early asthmatic responses during the 4 days; the mean maximum percent in FEV1 fall ranged between 19.5% and 22%. D5159 produced a slight inhibition of the LAR with maximum percent fall in FEV1 recorded as 28.8% +/- 5.0% for D5159 versus 34.1% +/- 4.8% for placebo (p < 0.05). There was a greater reduction recorded after administration of the two doses of budesonide. The mean LAR was 15.1% +/- 3.8% for 200 microg of budesonide and 11.2% +/- 2.3% for 800 microg of budesonide (p < 0.01 compared with placebo and D5159). The two doses of budesonide were not statistically different. Airway responsiveness to methacholine increased by 1.07 doubling doses 24 hours after allergen challenge. This increased airway responsiveness was slightly, but not significantly, reduced by the three active treatments (0.6 to 0.91 doubling doses).. The allergen-induced LAR model was able to differentiate a single dose of an active inhaled corticosteroid from placebo and a highly potent inhaled corticosteroid from a weak inhaled corticosteroid. The model did not differentiate between 2 fourfold doses of the highly active inhaled corticosteroid (at the doses used in this study), neither for the fall in FEV1 nor for the increase in airway hyperresponsiveness.

Topics: Administration, Inhalation; Administration, Topical; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hypersensitivity, Immediate; Male; Methacholine Chloride; Pregnenediones

Tenascin and fibronectin are extracellular matrix glycoproteins expressed during morphogenesis and tissue repair. In the present study bronchial biopsies were studied by the morphometric method of immunocytochemistry to reveal the distribution of different tenascin and fibronectin isoforms as well as the presence of inflammatory cells in the airway mucosa of patients with chronic asthma (n = 32) and those with seasonal birch-pollen-sensitive asthma out of season (n = 17), both in comparison with healthy control subjects (n = 12). The results showed an increase in tenascin immunoreactivity in the bronchial subepithelial reticular basement membrane layer in patients with chronic asthma (p < 0.0001) and in those with seasonal asthma (p < 0.01) compared with control subjects. The tenascin immunoreactivity, appearing as an intense wide subepithelial band in asthma, was seen only occasionally in the basement membrane of control specimens. Instead, a diffuse immunoreaction against both total fibronectin and locally produced extradomain A fibronectin was similarly visible in the airway mucosa of both patients and control subjects. Despite the significant increase in the airway mucosa of eosinophils and lymphocytes in patients with chronic asthma (p < 0.0001 and p < 0.0001, respectively) and of eosinophils in patients with seasonal asthma (p < 0.001), there was no correlation between the number of these cell types and level of tenascin expression. In patients with birch-pollen-sensitive asthma during the birch-pollen season, inhaled corticosteroid treatment, budesonide 400 micrograms twice daily, decreased tenascin immunoreactivity, in comparison with effects of placebo (p = 0.01). Our results suggest that the higher amount of tenascin reflects disease activity in asthma and may be an indicator of a remodeling process rather than of injury itself.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Basement Membrane; Biopsy; Bronchi; Budesonide; Case-Control Studies; Chronic Disease; Female; Fibronectins; Humans; Immunohistochemistry; Male; Middle Aged; Seasons; Tenascin

In a previous single dosing study in asthmatic school children fluticasone propionate produced significantly greater suppression of overnight urinary cortisol excretion than budesonide at high doses of 800 micrograms/day or greater. The aim of this study was to assess whether conventional lower doses of both drugs cause adrenal suppression when given at steady state twice daily by large volume spacer on a microgram equivalent basis in asthmatic school children.. Eight school children of mean age 12.1 years with stable asthma of mild to moderate severity (forced expiratory volume in one second (FEV1) 78.6% predicted, mid forced expiratory flow rate (FEF25-75) 72.5% predicted), on 400 micrograms/day or less of inhaled corticosteroid, were studied in a single blind (investigator blind), placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate 100 micrograms bid and 200 micrograms bid. Each dose was given at 08.00 hours and 20.00 hours for four days by metered dose inhaler via their respective large volume spacers with mouth rinsing. Measurements were made of overnight urinary cortisol and creatinine excretion after the eighth dose.. Neither drug produced significant suppression of overnight urinary cortisol or cortisol/creatinine excretion compared with pooled placebo and there were no differences between the drugs. Only one subject with each drug at 200 micrograms twice daily had abnormally low urinary cortisol excretion of < 10 nmol/12 hours. Ratios for the fold difference between active treatment versus placebo for urinary cortisol excretion were (as means and 95% confidence intervals for difference): budesonide 100 micrograms b.i.d 1.03 (95% CI 0.46 to 1.61), budesonide 200 micrograms b.i.d 1.04 (95% CI 0.62 to 1.46); fluticasone 100 micrograms b.i.d 1.11 (0.45 to 1.77), fluticasone 200 micrograms b.i.d 1.12 (0.78 to 1.47). Likewise, there were no significant differences in overnight urinary cortisol/creatinine excretion.. With repeated twice daily administration at steady state across a dose range of 200-400 micrograms/day no evidence of significant adrenal suppression was found using the sensitive marker of overnight urinary cortisol excretion for either fluticasone propionate or budesonide given via a large volume spacer. These results emphasise the good safety profile in children of these inhaled steroids at conventional dose levels, which have proven antiasthmatic efficacy.

Topics: Adrenal Cortex; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Creatinine; Cross-Over Studies; Drug Administration Schedule; Drug Delivery Systems; Fluticasone; Humans; Hydrocortisone; Nebulizers and Vaporizers; Single-Blind Method

Previous studies have shown that asthmatics have hyperinflation as defined by larger total lung capacity. The present study was set up in order to document changes in asthma clinic, airway calibre, airway reactivity and lung volumes after budesonide treatment. After a 2-week run-in period, 28 children with moderate persistent asthma were treated in a double-blind manner either with budesonide (0.4 mg/day) or placebo for 8 weeks and, thereafter, all patients were treated with open-label budesonide for a further 20 weeks. Symptoms, bronchodilator requirements and airway calibre improved significantly after 8 weeks of treatment (p < 0.05 for each) and prolonged treatment did not cause any further improvement. Reduction in hyperreactivity was apparent only after 20-28 weeks of treatment. Total lung capacity decreased along with budesonide treatment in both groups suggesting that early introduction of an inhaled corticosteroid may be useful in the prevention of asthma-related remodelling of the lung and thoracic cage.

Topics: Administration, Inhalation; Airway Resistance; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Total Lung Capacity; Treatment Outcome

The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.. After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.. The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.. In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Inhaled glucosteroids and oral theophylline are widely used to treat asthma. We compared the benefits of adding theophylline to inhaled glucosteroid with those of doubling the dose of inhaled glucosteroid in patients with persistent symptoms despite the use of inhaled glucosteroid.. In a double-blind, placebo-controlled trial, we randomly assigned 62 patients to receive either 400 microg of inhaled budesonide (low-dose budesonide) with 250 or 375 mg of theophylline (depending on body weight) or 800 microg of inhaled budesonide (high-dose budesonide). All doses were given twice daily for three months. Lung function was measured serially, and patients kept records of peak expiratory flow, symptoms, and albuterol use. The effects of treatment on endogenous cortisol levels were also assessed.. Both treatments resulted in improvements in lung function that were sustained throughout the study. As compared with treatment with high-dose budesonide, treatment with low-dose budesonide plus theophylline resulted in greater improvements in forced vital capacity (P=0.03) and forced expiratory volume in one second (P= 0.03). There were significant and similar reductions in beta2-agonist use and the variability of peak expiratory flow, a correlate of bronchial hyperresponsiveness and the severity of asthma. Serum cortisol concentrations were significantly reduced in the group given high-dose budesonide (from a mean [+/-SE] of 18.4+/-2.4 microg per deciliter to 15.9+/-2.1 microg per deciliter, P=0.02) but were unchanged in the other group. The median serum theophylline concentration was 8.7 microg per milliliter (therapeutic range, 10 to 20) among those who received theophylline. Both treatments were well tolerated.. For patients with moderate asthma and persistent symptoms, low-dose inhaled budesonide with theophylline and high-dose inhaled budesonide produced similar benefits. Effects were achieved at theophylline concentrations below the recommended therapeutic range. The addition of low-dose theophylline to inhaled glucosteroid may be preferable to and cheaper than increasing the dose of inhaled glucosteroid.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Theophylline; Vital Capacity

The aim of our study was to compare basal unstimulated levels of plasma cortisol and adrenocorticotropic hormone (ACTH) with stimulated levels produced by the corticotropin releasing factor (CRF) test in asthmatics taking high-dose inhaled steroid therapy. In theory, the CRF test would appear to be a suitable replacement for tetracosactrin (cosyntropin) (synthetic ACTH) as a test of hypothalamic-pituitary-adrenal (HPA) axis suppression.. Ten patients with stable asthma and a mean age of 28.8 years, FEV1 of 88.9% predicted, and forced expiratory flow between 25% and 75% of FVC of 57.0% predicted, were studied in a double-blind placebo-controlled crossover design comparing 4 days with budesonide, 1,000 microg bid, and placebo. Each dose was given at 8 AM and 10 PM for 4 days by metered-dose inhaler. Measurements were made at steady-state of basal 8 AM plasma cortisol and ACTH 10 h after the eighth dose, and CRF test (100-microg i.v. bolus) was then performed.. The results for 8 AM plasma cortisol (nmol/L, means and 95% confidence interval [CI] for difference) showed that budesonide produced significant suppression compared with placebo: budesonide (284.1) vs placebo (360.9) (95% CI, 9.3 to 144.3). Suppression also occurred for peak plasma cortisol in response to CRF: budesonide (375.9) vs placebo (470.2) (95% CI, 27.0 to 161.6). ACTH (ng/L, means and 95% CI for difference) demonstrated a similar nonsignificant trend to cortisol, with suppression in both basal and stimulated forms: 8 AM ACTH, budesonide (36.6) vs placebo (42.2) (95% CI, -2.6 to 13.8); CRF peak response, budesonide (49.9) vs placebo (62.8) (95% CI, -3.6 to 29.5).. In asthmatic patients receiving inhaled budesonide, 1,000 microg bid, the suppression of basal unstimulated 8 AM plasma cortisol was mirrored by the suppression of the CRF stimulation response. These results highlight the point that when basal 8 AM plasma cortisol levels are suppressed, a comparable degree of dynamic impairment of HPA axis response is also likely to be found with physiologic testing.

Topics: Administration, Inhalation; Administration, Topical; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents; Asthma; Biomarkers; Budesonide; Corticotropin-Releasing Hormone; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Flow Rates; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Predictive Value of Tests; Radioimmunoassay

Short-term lower leg growth, the insulin-like growth factor axis, and collagen turnover were assessed in 16 adolescents with asthma during treatment with inhaled budesonide, 800 micrograms/d, from a pressurized metered dose inhaler with a volume spacer. The design was a randomized double blind, placebo-controlled two-period crossover trial with treatment periods of 4 weeks and a 1-week wash-out. Lower leg growth was assessed by knemometry. Serum levels of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, and the following markers of collagen turnover were evaluated: Serum markers of type I collagen formation and degradation; the carboxy-terminal propeptide of type I procollagen and the carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen (ICTP), the serum marker of type III collagen formation; the amino-terminal propeptide of type III procollagen (PIIINP) and the urinary concentrations of the type I collagen degradation products pyridinoline (PYD) and deoxypyridinoline (DPD) cross-links. Mean lower leg growth velocity was suppressed from 0.51 mm/week during placebo to 0.18 mm/week during budesonide treatment (p < 0.001). No statistically significant effects on insulin-like growth factor-1, insulin-like growth faster-binding protein-3, or carboxy-terminal propeptide of type I procollagen were observed. ICTP and PIIINP were reduced with 2.3 and 2.5 micrograms/liter (p < 0.001 and p < 0.001, respectively) during budesonide treatment, urinary concentrations of PYD and DPD with 32.9 nmol/mmol creatinine (p < 0.005) and 6.8 nmol/mmol creatinine (p < 0.005), respectively. Significant correlations between lower leg growth velocity and ICTP, PIIINP, PYD, and DPD during placebo (p < 0.01, p < 0.05, p < 0.01, and p < 0.01) and budesonide (p < 0.05, p < 0.05, p < 0.05, and p < 0.05) periods were found. Short term lower leg growth suppression in adolescents treated with inhaled budesonide, 800 micrograms/d, reflects suppression of type I and III collagen turnover.

Topics: Administration, Topical; Adolescent; Amino Acids; Anti-Inflammatory Agents; Asthma; Bone Development; Budesonide; Child; Collagen; Collagen Type I; Female; Glucocorticoids; Growth Disorders; Humans; Leg; Male; Peptide Fragments; Peptides; Procollagen

The aim of this study was to investigate whether treatment with a low daily dose of 400 microg inhaled budesonide (Pulmicort Turbuhaler) in newly diagnosed asthmatics could influence the course of asthma. Seventy five adult patients, mostly with mild asthma, diagnosed during the previous year and bronchial hyperresponsiveness, participated in a double-blind, randomized, parallel-group multicentre study. They were treated with budesonide 200 microg b.i.d. or placebo, delivered via Turbuhaler for 12 months and followed-up for another 6 months without inhaled steroid treatment. Airway function, symptom scores, reactivity to histamine and inflammatory indices in blood were assessed. The mean increase in morning peak expiratory flow (PEF) was 28 L x min(-1) after budesonide treatment compared with no increase in the placebo group (p=0.011). The provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) (geometric mean) increased in the budesonide group by approximately two doubling dose steps, but not in the placebo group (p=0.0003). The difference between groups with regard to improvement in asthma symptom scores and inflammatory indices did not reach statistical significance. During the 6 month follow-up, the PEF values of the patients who had previously been treated with budesonide decreased by 18 L x min(-1) while the PD20 decreased by approximately one doubling dose step. In conclusion, early treatment with a low dose of budesonide improves airway function and decreases bronchial responsiveness, but the improvements are short-lasting without continued treatment.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Asthma; Bias; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Selection; Prognosis; Respiratory Function Tests

In a group of 55 children in the age of 7-14 years with mild or severe asthma, the evaluation of inhaled budesonide (in pulmicort and horacort) effect on bronchial reactivity and adrenal cortex function was made. Budesonide in dose 640 mg or 800 mg daily was administered during 6 weeks. In addition fenoterol was administered in dose 2 x 200 mg daily. Lung function tests, a histamine provocation and cortisol level in serum were done before, after 2 weeks and after 6 weeks in the course of treatment. Effective control upon the disease was observed in 67.9% and 70.4% patients. The result of the treatment was significant decrease in bronchial reactivity toward a histamine. Decrease of FEV1-32% and -34% in the first study was improved after two weeks up to -24% and -17% and after six weeks it achieved-12%. The level of endogenous cortisol in serum didn't show significant decrease in the course of therapy. The ratio of benefits and risk of side effects in the course of budesonide in medium dose during six weeks indicates clearly the first ones.

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Child; Drug Therapy, Combination; Female; Fenoterol; Histamine; Humans; Male; Respiratory Function Tests

Budesonide, an inhaled corticosteroid and specific immunotherapy, are both routinely used in the treatment of bronchial asthma. However, there are as yet, no studies comparing the effects of budesonide vs immunotherapy.. The aim of this study is to compare the effects of budesonide with immunotherapy in patients having perennial asthma.. This study is an open, parallel, comparative trial, in which 51 young patients were administered either immunotherapy or budesonide for 1 year and their global symptom scores and FEV1 values assessed. Both treatments were abruptly discontinued after 12 months and the effects of cessation analysed.. The use of budesonide resulted in a faster and more striking improvement during the first few months as compared to immunotherapy, with an even more rapid decline in benefits on cessation of budesonide. Immunotherapy on the other hand, resulted in slow but steady improvement which did not decline as rapidly as budesonide on cessation.. Although this was an open trial, it could be concluded that relief with inhaled corticosteroids in bronchial asthma is more rapid than immunotherapy; however the decline in benefit on cessation of inhaled corticosteroid is even more rapid, a phenomenon not seen with immunotherapy.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Desensitization, Immunologic; Humans

Exhaled nitric oxide (NO) is elevated in untreated patients with asthma but not in patients treated with inhaled glucocorticoids. This may reflect an inhibitory effect of glucocorticoids on the induction of the enzyme NO synthase in the respiratory tract. We have now studied the effect of an inhaled glucocorticoid (budesonide 800 micrograms twice daily via a dry powder delivery system for 3 wk) on exhaled NO in 11 patients with mild asthma in a double-blind crossover randomized-order placebo-controlled study. Exhaled NO was reduced from a baseline value of 203 +/- 29 parts per billion (ppb) to 120 +/- 26 ppb after 3 wk of treatment (p < 0.01), whereas there was no change after a matched placebo (169 +/- 20 at baseline compared with 184 +/- 16 ppb after 3 wk). A significant and progressive fall in exhaled NO was found from 1 to 3 wk. There was no significant change in FEV1 after inhaled steroids (although mean FEV1 was 92% predicted normal at baseline), although there was a reduction in airway responsiveness to methacholine (approximately 2.5 doubling dilutions). These results add further support to the view that the elevated levels of exhaled NO in asthma may derive from induction of an inducible isoform of NO synthase and indicate that exhaled NO may be a useful way of monitoring the anti-inflammatory effects of glucocorticoids and other anti-inflammatory treatments in asthma.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosols; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Luminescent Measurements; Male; Monitoring, Physiologic; Nitric Oxide; Placebos; Powders; Pregnenediones

Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase of airway obstruction and increase of airway responsiveness after cessation of treatment. We investigated whether anti-inflammatory therapy may affect these rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and after cessation of 2 wk of regular treatment with placebo and low-dose (250 micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr, mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were studied. One group (n = 16) was randomized to budesonide treatment, 400 micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1 were measured 10, 14, 34, and 82 h after the last terbutaline or placebo inhalation. A different method of statistical analysis was used, in that measurements performed at 10, 14, and 34 h were expressed relative to 82 h values in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly change during placebo and budesonide treatment. Mean PC20 and morning and evening peak expiratory flow were significantly higher during budesonide treatment (p < 0.01). PC20 did not significantly change after cessation of terbutaline treatment in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation of treatment with both doses of terbutaline were significantly different from the 82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the last terbutaline and placebo inhalation in the placebo group compared with the budesonide treatment group (p = 0.02). We conclude that cessation of regular treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does not result in a significant rebound airway responsiveness in patients with mild asthma. However, the results suggest a small rebound bronchoconstriction that does not occur when asthmatic patients are also treated with budesonide.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aerosols; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Ipratropium; Male; Methacholine Chloride; Middle Aged; Placebos; Pregnenediones; Terbutaline; Time Factors

To compare the efficacy of self management of asthma with traditional treatment.. 12 month prospective randomised trial.. Outpatient clinics in Finland.. 115 patients with mild to moderately severe asthma.. Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements.. Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life.. The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare.. Self management reduces incidents caused by asthma and improves quality of life.

Topics: Adult; Aged; Ambulatory Care; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Beclomethasone; Budesonide; Female; Finland; Glucocorticoids; Hospitalization; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Patient Education as Topic; Peak Expiratory Flow Rate; Pregnenediones; Prospective Studies; Quality of Life; Risk Factors; Self Care; Single-Blind Method; Treatment Outcome

The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects. For this purpose 85 allergic and nonallergic asthmatic subjects were randomized into three groups, which were given high-dose (1,600 micrograms/d) inhaled budesonide, low-dose (400 micrograms/d) inhaled budesonide, and oral theophylline (600 mg/d), respectively, and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein (ECP), eosinophil protein x/eosinophil derived neurotoxin (EPX/EDN) as eosinophil markers, and myeloperoxidase (MPO) and lactoferrin (LF) as neutrophil markers. Lung functions (FEV1% predicted, and histamine PC20) and the eosinophil markers ECP and EPX/EDN were improved and reduced, respectively, by budesonide in a dose-dependent and temporally parallel fashion. Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment. The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects, since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide. MPO but not LF was reduced after several months of treatment in all three groups, but only in nonsmokers. We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids.

Topics: Adult; Aerosols; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Blood Proteins; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Inflammation Mediators; Lactoferrin; Lung; Male; Middle Aged; Neurotoxins; Neutrophils; Peroxidase; Pregnenediones; Ribonuclease, Pancreatic; Ribonucleases; Smoking; Theophylline

Twice-daily inhaled salmeterol produces rapid reduction in its acute bronchoprotective effect against methacholine in patients with mild asthma. This investigation examined this effect in patients with moderate asthma who were using inhaled corticosteroids.. Eight asthmatic volunteers who required inhaled corticosteroids for control of their symptoms and who were able to withhold treatment with beta 2-agonists for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 microg twice a day for seven doses, and placebo in similar fashion, with a 7-day or greater washout between these periods. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler, 10 min post-200 microg salbutamol.. Baseline FEV1 measurements before doses 3, 5, and 7 of salmeterol, ie, 12 h after salmeterol, were significantly higher than all other baseline values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) following the third dose of salmeterol (6.8 mg/mL) was significantly lower than after the first dose of salmeterol (12.0 mg/mL; p=0.031), and this reduction of bronchoprotection persisted following doses 5 and 7. The methacholine PC20 10 min postsalbutamol measured after the salmeterol period was significantly lower than after placebo (5.6 vs 13.3 mg/mL; p<0.001).. Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and persisted after the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was also significant after regular use of salmeterol for seven doses. These effects, in subjects using inhaled corticosteroids regularly, were similar to the those previously seen in patients with mild asthma using as-required beta 2-agonists only, indicating that tolerance is not prevented by use of inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Placebos; Pregnenediones; Salmeterol Xinafoate; Tachyphylaxis

Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids. In a blind parallel-group study for 18 weeks, 102 children, mean age 22 (5- 47) months, were randomized for treatment starting with 0.25 or 1 mg b.i.d. The patients were reviewed every 3 weeks, and if symptom control had been achieved the dose was reduced, otherwise it was kept. The clinical effect was very good with both dose regimens. The median time to 7 consecutive days without any asthma symptoms was about 1 month with both, highlighting the importance of the duration of therapy rather than the benefits of a high starting dose. In 18 of 24 children who attained the placebo stage, symptoms had reappeared at the last visit. Although an overall minimal effective maintenance dose could not be demonstrated, 47% achieved symptom control on 0.25 mg b.i.d., i.e. fulfilled criteria for further dose reduction. No significant side effects were seen. On average, 25% of the nominal dose reached the patients.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Infant; Nebulizers and Vaporizers; Pregnenediones; Severity of Illness Index; Treatment Outcome

An open, randomized, parallel-group study was conducted to investigate whether asthmatic patients, considered adequately treated with a corticosteroid and/or short-acting beta 2-agonist via pressurized metered-dose inhaler (pMDI), could be transferred to a corresponding nominal dose of budesonide and/or terbutaline via Turbuhaler, an inspiratory flow-driven multidose dry powder inhaler (Astra Draco; Lund, Sweden), without a decrease in the effect of treatment. One thousand four patients (555 women; mean age, 44 years; mean peak expiratory flow [PEF], 102% predicted normal value) were randomized and treated with either pMDI (current therapy) or Turbuhaler for 52 weeks. The variables studied were asthma-related events, morning PEF, and inhaler-induced clinical symptoms. Asthma-related events were defined in two ways: (1) sum of health-care contacts plus doublings or additions of steroids, and (2) number of 2 consecutive days with PEF less than 80% of baseline. Baseline was obtained from a 2-week run-in period while receiving previous therapy. No statistically significant difference was found in asthma-related events according to definition 1. According to definition 2, there was a statistically significant difference between the groups in favor of Turbuhaler (p = 0.008). The mean number of events was 1.7 with Turbuhaler and 2.2 with pMDI. The mean number of weeks per patient with a PEF less than 90% of baseline was 4.5 with Turbuhaler compared with 6.0 with pMDI (p = 0.002). The sum of inhaler-induced symptoms after 1 year of use was statistically significantly lower with Turbuhaler (0.40) than with pMDI (0.75) (p = 0.0001). In conclusion, budesonide and terbutaline in Turbuhaler offered a superior alternative to corticosteroids and bronchodilators delivered by pMDIs in the maintenance treatment of asthma.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Female; Glucocorticoids; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnenediones; Terbutaline

The aim of this open study was to observe linear growth in young children with asthma treated with nebulized budesonide. Infants and young children (< 3 years old) with severe uncontrolled asthma were studied. They were treated with nebulized budesonide (1-4 mg day-1) and treated for at least 6 months. Height standard deviation scores (HtSDS) were measured before ("pre-measurements") immediately prior to commencing nebulized budesonide therapy (baseline) and after at least 6 months of therapy ("post-measurements"). The mean HtSDS score at pretreatment was -0.21 and at baseline had fallen further to -0.46. The mean HtSDS increased to -0.17 when the post-measurements were made (p = 0.035) after at least 6 months of nebulized budesonide therapy. Treatment with nebulized budesonide for longer than 6 months in very young children with severe asthma was not associated with reduced linear growth.

Topics: Administration, Inhalation; Age Factors; Asthma; Body Height; Bronchodilator Agents; Budesonide; Child, Preschool; Growth Disorders; Humans; Infant; Nebulizers and Vaporizers; Pregnenediones; Prospective Studies; Time Factors

11 patients with severe bronchial asthma entered a randomized trial of glucocorticosteroid budesonide of Russian produce. Of them 6 patients received inhalations of budesonide (800 micrograms/day for 6 months), 5 control patients did not receive the drug. As shown by investigations of external respiration and bronchoalveolar lavage with estimation of cytogram, metacholine provocative tests, fiber bronchoscopy, budesonide inhalations relieved clinical symptoms of asthma, bronchial hyperreactivity and inflammation.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchitis; Bronchodilator Agents; Bronchoscopy; Budesonide; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

Treatments with inhaled corticosteroids yielded conflicting results in infants with severe asthma. The purpose of this study was to assess the efficacy of nebulized budesonide on the control of asthma in this age group.. In a double-blind, placebo-controlled study, 40 infants with severe asthma received either nebulized budesonide (1 mg) or placebo twice daily for 12 weeks, followed by a follow-up period of up to 12 weeks. A jet nebulizer driven by an air compressor was used to administer budesonide and placebo.. Fewer patients in the budesonide group had an exacerbation during the treatment period (40%) compared with the placebo group (83%, p < 0.01). The duration of oral steroid therapy was shorter in the budesonide group than in the placebo group (median number of days of exacerbation as a proportion of the total treatment time, 0% vs 14.5%; p < 0.05). The incidence of daytime (p < 0.05) and nighttime wheezing (p < 0.01) was lower in the budesonide group than in the placebo group during the treatment period. The proportion of patients without an exacerbation of asthma during the entire 24 weeks was 28% for those patients who had received budesonide and 0% for those patients who had received placebo. Asthma improved in more patients in the budesonide group (17 and 19, 89%) than in the placebo group (7 of 16, 44%; p < 0.005). These results should improve and modify the treatment of infants with severe asthma.. Nebulized budesonide (1 mg twice daily) is a well-tolerated and efficient treatment for severe infantile asthma.

Topics: Aerosols; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Pregnenediones

A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients.. Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later.. Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8).. Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Topics: Administration, Topical; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aerosols; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Pregnenediones

Our aim was to assess the efficacy of budesonide (Pulmicort Turbohaler Astra) used as part of a self-management plan in a group of patients with chronic asthma. One hundred and twenty five patients with nocturnal asthma symptoms, despite the use of inhaled prophylactic and beta 2-agonist therapy, were randomized to inhaled budesonide 200, 400 or 800 micrograms b.i.d. either with dose adjustments made by the physician, i.e. doctor-managed (DM; n = 64), or as part of a self-management plan (SM; n = 61). The SM group were allowed to adjust their dose according to written guidelines based on morning peak flow. At the end of the 6 month treatment period, there were no significant differences detected between the DM and the SM groups either from the clinic or diary card data. Both groups demonstrated a significant reduction in the number of sleep-disturbed nights, by 75% in the DM group and 77% in the SM group, at the end of the study. In conclusion, for patients with mild-to-moderate asthma, either a doctor-adjusted dose regimen or a peak flow based self-management plan involving budesonide is equally efficacious. For some patients, a simple regimen, adjusted by the physician at clinic visits, may be easier to follow.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Budesonide; Chi-Square Distribution; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Self Administration; Treatment Outcome

Topics: Administration, Topical; Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone and Bones; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Osteocalcin; Pregnenediones

A "survival" model offers certain ethical and practical advantages over alternative experimental designs if used to compare antiasthmatic inhaled steroid formulations. The model requires an objective daily measure of therapeutic effect (e.g., peak expiratory flow rate, which may be expressed as the lower of two daily measurements (LPF) or as diurnal variability (DVPF). The relative efficiency of these two measures is unknown.. This study was conducted to determine the relative efficiency of LPF and DVPF.. We analyzed data from a placebo-controlled comparison of an active inhaled formulation of budesonide versus an inactive oral formulation. The primary outcome measure in this design is the number of days from the time the test treatments start until a statistically significant deterioration occurs from an optimal asthma control value established at baseline.. DVPF proved less sensitive than LPF; that is, fewer patients relapsed during the 8-week trial period: 32 versus 41, respectively. Also, the median interval until relapse was longer: 24 versus 9 days. With LPF, inhaled budesonide proved more effective than placebo or oral budesonide (p = 0.03), whereas DVPF failed to discriminate among the test treatments (p = 0.38). LPF correlated with all three symptom indices (p > or = 0.003) and two of three spirometric indices measured concomitantly (p < or = 0.04). DVPF did not correlate with any index (p > or = 0.10).. In this experimental model, LPF proved more sensitive and valid than DVPF as an indicator of differences in antiasthmatic potency between two inhaled steroid formulations.

Topics: Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Circadian Rhythm; Double-Blind Method; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones; Retrospective Studies

The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2-28) mg.day-1, and the mean dose of inhaled steroids administered was 2.3 (1.6-3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg.day-1 during the last 2 placebo weeks but only 7.9 mg.day-1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aerosols; Analysis of Variance; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Folic Acid Antagonists; Forced Expiratory Volume; Humans; Male; Methotrexate; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones

The aim of this study was to assess the efficacy and safety of inhaled salmeterol 100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB), both via the Diskhaler, when added to concurrent treatment, in asthmatic patients who were not controlled on high doses of inhaled steroids (> or = 1,500 micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a multicentre, parallel group, double-blind study in which 190 patients with a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) of 30-75% predicted and 15% reversibility to inhaled bronchodilator were randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from 281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1 (p < 0.001). The SM group showed significantly better reduction in diurnal variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37 L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L). The SM group had significantly more symptom-free nights than the SB group (p < 0.001), and also more "rescue-free" nights (p = 0.04). The adverse event profile was similar in both groups. This study indicates that in asthmatic patients, not controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d. significantly improves lung function and reduces asthma symptoms.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Circadian Rhythm; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos; Pregnenediones; Salmeterol Xinafoate

The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.

Topics: Administration, Topical; Adolescent; Aerosols; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone and Bones; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hydroxyproline; Male; Nebulizers and Vaporizers; Osteocalcin; Patient Satisfaction; Peak Expiratory Flow Rate; Peptide Fragments; Pregnenediones; Procollagen; Surveys and Questionnaires

There is increasing evidence for the development of tolerance to the protective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli. Animal studies have suggested that glucocorticoids protect against the down-regulation of beta 2-receptors after chronic exposure to beta 2-agonists. In a double-blind placebo-controlled crossover study in 12 patients with mild asthma, we investigated the effect of inhaled budesonide or identical placebo on the protection conferred by albuterol (200 micrograms) against methacholine-induced bronchoconstriction before and after treatment with the long-acting beta 2-agonist salmeterol. Patients were randomized to be treated for 3 wk with inhaled budesonide (800 micrograms twice a day) or placebo; salmeterol (50 micrograms twice a day) was added during the third week. Airway responsiveness to methacholine was measured 15 min after albuterol, both before and exactly 12 h [corrected] after the last salmeterol dose. Mean FEV1 increased significantly after 2 wk of budesonide (p < 0.05) and increased further after salmeterol (p < 0.05) compared with placebo. After 2 wk, the bronchoprotective effect of albuterol against methacholine was significantly greater with budesonide than with placebo (3.4 versus 2.4 doubling dilutions; p < 0.05), consistent with an improvement in airway hyperresponsiveness with budesonide therapy. However, regular salmeterol treatment for 1 wk significantly diminished the protection conferred by albuterol against methacholine challenge, both with budesonide and with placebo (-1.1 +/- 0.42 and -1.41 +/- 0.30 doubling dilutions, respectively). There was no significant difference in the loss of bronchoprotection seen with salmeterol between budesonide and placebo treatment periods. Our study suggests that even a high dose of an inhaled glucocorticoid fails to prevent the loss of bronchoprotection produced by regular beta 2-agonist therapy.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Inflammatory Agents; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Pregnenediones; Salmeterol Xinafoate

The rebound increase in bronchial reactivity and fall in forced expiratory volume in one second (FEV1) following treatment with beta agonists seen in several studies has occurred regardless of concurrent steroid therapy. Little is known about the effect of adding beta agonists to corticosteroids, but in a recent study regular treatment with terbutaline appeared to reduce some of the beneficial effects of budesonide. The effects of budesonide alone and in combination with regular terbutaline treatment on lung function, symptom scores, and bronchial reactivity were therefore examined.. Sixteen subjects with mild stable asthma inhaled budesonide 800 micrograms twice daily for two periods of 14 days with terbutaline 1000 micrograms three times daily or placebo in a double blind crossover fashion. FEV1 and the dose of histamine or adenosine monophosphate (AMP) causing a 20% fall in FEV1 (PD20) were measured before and 12 hours after the final dose of treatment, and changes from baseline were compared. Seven day mean values for daily morning and evening peak expiratory flow (PEF) values, symptom scores, and rescue medication were compared before and during treatment.. Morning and evening PEF rose more with budesonide plus terbutaline than with budesonide alone, with a mean difference of 19 l/min occurring in the evening (95% confidence interval (CI) 2 to 36). There was no difference in symptom scores during treatment. Following treatment the mean increase in FEV1 was 150 ml higher with budesonide alone (95% CI-10 to 300). There was no difference between treatments in change in histamine and AMP PD20.. Evening PEF was greater when budesonide was combined with regular terbutaline. There was no evidence of a difference in bronchial reactivity following the two treatment regimens. The findings of a previous study were not confirmed as the reduction in FEV1 after budesonide and terbutaline was smaller and not statistically significant. Further work is needed to determine whether this disparity in findings in the two studies is due to a type 2 statistical error in this study or a spurious finding in the previous study.

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones; Terbutaline

Although corticosteroids are recognised as the most efficacious treatment for bronchial asthma, their mode of action remains unclear. A placebo controlled trial was undertaken of the effect of inhaled corticosteroids on physiological and immmunopathological parameters in asthmatic patients in whom the correlations between these indices were tested after treatment.. Sixteen patients (two women) with asthma entered a double blind, placebo controlled, parallel study during which they inhaled either budesonide 800 micrograms twice daily or matching placebo for six weeks. Spirometric parameters and bronchial reactivity to histamine and terbutaline were measured and endobronchial biopsy samples were taken before and after treatment. Patients recorded morning and evening flow rates during the treatment period. The biopsy samples were subjected to immunohistological analysis to determine the disposition of inflammatory cells within the bronchial wall.. Treatment with budesonide resulted in a significant improvement in the 25-75% forced expiratory flow (FEF25-75) from a mean of 133 l/min before treatment to 169 l/min after treatment, and in the morning peak expiratory flow rate (PEFR) from a mean of 384 l/min before treatment to 415 l/min after treatment. No changes were seen in the placebo group. Comparison between the changes in the immunopathological indices after six weeks of treatment with placebo or budesonide showed a significant reduction in the numbers of mast cells (0.5/unit area to 0.2/ unit area), activated eosinophils, and the expression of HLA-DR antigens (relative density -1.9 before to 1.02 after treatment) on inflammatory cells in response to treatment with budesonide. Although reductions in the numbers of other inflammatory cells within the bronchial wall were recorded using immunohistological analysis, these changes were not statistically significant. Significant correlations were found between changing immunological indices and lung physiology.. This controlled study shows that inhaled corticosteroids cause improvement in physiological and immunopathological parameters in patients with stable asthma that are not seen with placebo, and that cause and effect relationships may exist between these two measures of disease status.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Bronchi; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Cell Count; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; HLA-DR Antigens; Humans; Male; Mast Cells; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones