budesonide--formoterol-fumarate-drug-combination and Asthma

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

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

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases that remain uncontrolled in many patients, despite the wide range of therapeutic options available. This review analyzes the available clinical evidence on 3 budesonide/formoterol DPI devices, Spiromax. The effectiveness of dry powder inhalers (DPI) depends largely on the device and the patient's inhaler technique. Equally important are the patient's perception of the inhaler and adherence. Given the high burden of these diseases, it is important that efforts be made to select the best DPI for each patient and to analyze the impact of these variables to help improve the health and quality of life of our patients. This review provides a comprehensive overview of the present knowledge about PROs, inhaler handling errors, and asthma and COPD control achieved by Spiromax

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Dry Powder Inhalers; Humans; Patient Reported Outcome Measures; Pulmonary Disease, Chronic Obstructive; Quality of Life

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

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

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Ambulatory Care; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Chronic Disease; Drug Combinations; Humans

The goal of asthma management is to achieve optimal asthma control, defined by the absence of daytime symptoms, nighttime waking, reliever use, functional limitation, and lung function stability, and to also reduce the future risks of asthma exacerbations, deterioration in lung function, and the medication's adverse effects. The most widely used maintenance therapy is inhaled corticosteroids (ICSs). This review considered the evidence in which the combination of the ICS budesonide and the rapid-onset long-acting β-agonist (LABA) formoterol can be used as a standard of care for maintenance and reliever therapy in moderate to severe asthma.. The archival literature of peer-reviewed studies on the efficacy and safety of budesonide-formoterol as maintenance and reliever therapy in moderate to severe asthma.. The ICS-LABA combination containing budesonide-formoterol reduces future risk of severe asthma exacerbations and provides similar levels of day-to-day asthma control when compared with using high-dose ICS alone, or combination ICS-LABA therapy and short-acting β. Budesonide-formoterol as a single combination maintenance and reliever inhaler is effective in reducing asthma exacerbation risk, requires a lower maintenance dose of ICS, and results in a simplified approach to asthma management.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Humans; Nebulizers and Vaporizers; Standard of Care

Topics: Asthma; Budesonide, Formoterol Fumarate Drug Combination; Eosinophils; Humans; Mometasone Furoate; Sputum; Tiotropium Bromide

The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations.. A systematic literature review was undertaken to identify randomised controlled trials (RCTs) in which randomised treatments included either i) budesonide/formoterol reliever monotherapy versus budesonide/formoterol fixed dose maintenance with short acting beta agonist (SABA) reliever therapy, or ii) budesonide/formoterol reliever therapy in addition to budesonide/formoterol maintenance versus higher fixed dose maintenance budesonide/formoterol with SABA as reliever therapy. Eligible studies were reviewed to allow determination of the relative potency and efficacy of the comparator regimens to reduce the risk of a severe exacerbation.. The one RCT of budesonide/formoterol reliever monotherapy showed a 4.6-fold (95% CI 2.9 to 7.3) greater potency than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of severe exacerbations. In the one RCT that compared budesonide/formoterol maintenance and reliever therapy with higher fixed dose maintenance budesonide/formoterol plus SABA reliever therapy, there was an additional 26% (95% CI 4 to 42%) reduction in severe exacerbation risk with the addition of budesonide/formoterol reliever therapy to maintenance budesonide/formoterol, despite a 25% lower total budesonide/formoterol dose.. The limited available evidence suggests that budesonide/formoterol reliever therapy has greater potency and efficacy than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of a severe exacerbation. This is an important concept which has the potential to guide clinical practice in asthma, although the small number of studies available highlights the need for further research to better define these pharmacological properties.

Topics: Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Dose-Response Relationship, Drug; Drug Combinations; Humans; Randomized Controlled Trials as Topic; Retrospective Studies

Asthma has been demonstrated to be as common in the elderly as in younger age groups. Although no specific recommendations exist to manage the disease differently in older individuals, functional features and clinical presentations may be affected by age per se, and by age-related conditions, such as comorbidities and polypharmacy. In this review article, we aimed to explore the efficacy and safety in elderly asthmatic patients of one of the most currently used inhaled treatments for asthma, that is, the fixed-dose combination of budesonide/formoterol. We attempted to address some practical questions that are relevant to the daily practice of clinicians. We focused on the efficacy and real-world effectiveness of inhaled corticosteroids and long-acting β-adrenergic bronchodilators (ICS/LABA) as treatment in the elderly population, since data are extrapolated from younger populations. We investigated whether a maintenance and reliever therapy approach is more effective in the elderly as opposed to maintenance regimens, from both the general practitioner's and the pulmonologist's perspective. To address these questions, we scanned electronic databases (PubMed, MEDLINE, Embase, Scopus and Google Scholar) from the date of inception up to October 2016 with a cross-search using the following keywords: 'asthma', 'elderly', 'SMART therapy', 'MART therapy', 'Turbuhaler', and 'budesonide/formoterol'. The available literature on the topic confirms that when the age-associated changes are properly managed in clinical practice, asthma in older populations can be optimally controlled with inhaled treatment including ICS/LABA. This also applies for the budesonide/formoterol fixed combination, thus allowing for the maintenance and reliever therapy approach.

Topics: Administration, Inhalation; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Databases, Factual; Drug Interactions; Humans; Middle Aged; Practice Guidelines as Topic; Treatment Outcome

In the treatment of chronic obstructive pulmonary disease (COPD), bronchodilators such as long acting muscarinic antagonist (LAMA) and long acting β agonist(LABA) play key roles for improving respiratory function and symptoms, and reducing risk of exacerbation. However, inhaled corticosteroid (ICS), a key medicine for bronchial asthma, is limitedly used in COPD treatment. Japanese Respiratory Society recommends to use ICS for severe COPD patients who have been frequently exacerbated, because previous clinical studies indicated that ICS reduces exacerbation in moderate to severe COPD patients. Asthma sometimes overlaps with COPD, and symptoms of those patients are not well controlled by the bronchodilation therapy alone. Therefore, ICS/LABA or ICS/LAMA should be prescribed to those overlapped patients. Concentration of exhaled nitrogen oxide and percentage of peripheral eosinophil may be good biomarkers for discriminating the COPD patients who have good response to ICS treatment.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Delayed-Action Preparations; Disease Progression; Drug Combinations; Drug Therapy, Combination; Eosinophils; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Muscarinic Antagonists; Nitrogen Oxides; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Severity of Illness Index; Tiotropium Bromide

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

An as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a pragmatic randomised controlled trial of budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild asthma, we recently reported that about two-thirds preferred as-needed combination preventer and reliever therapy. The aim of this study was to determine the relative importance of attributes associated with these two asthma therapies in this subgroup of participants who indicated their preferred treatment in the PRACTICAL study.. At their final study visit, a subgroup of participants indicated their preferred treatment and completed a discrete choice experiment using the Potentially All Pairwise RanKings of all possible Alternatives method and 1000minds software. Treatment attributes and their levels were selected from measurable study outcomes, and included: treatment regimen, shortness of breath, steroid dose and likelihood of asthma flare-up.. The final analysis dataset included 288 participants, 64% of whom preferred as-needed combination preventer and reliever. Of the attributes, no shortness of breath and lowest risk of asthma flare-up were ranked highest and second highest, respectively. However, the relative importance of the other two attributes varied by preferred therapy: treatment regimen was ranked higher by participants who preferred as-needed treatment than by participants who preferred maintenance treatment.. Knowledge of patient preferences for treatment attributes together with regimen characteristics can be used in shared decision-making regarding choice of treatment for patients with mild-moderate asthma.. ACTRN12616000377437.

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Decision Making, Shared; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Patient Participation; Patient Preference; Terbutaline

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

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

Dry powder inhalers containing the budesonide/formoterol combination have currently a well-established position among other inhaled products. Even though their efficacy mainly depends on the local concentrations of the drug they deliver within the lungs, their safety profile is directly related to their total systemic exposure. The aim of the present investigation was to explore the absorption and disposition kinetics of the budesonide/formoterol combination delivered via two different dry powder inhalers in asthma patients. Plasma concentration-time data were obtained from a single-dose, crossover bioequivalence study in asthma patients. Non-compartmental and population compartmental approaches were applied to the available datasets. The non-compartmental analysis allowed for an initial characterization of the primary pharmacokinetic (PK) parameters of the two inhaled drugs and subsequently the bioequivalence assessment of the two different dry powder inhalers. The population pharmacokinetic analysis further explored the complex absorption and disposition characteristics of the two drugs. In case of inhaled FOR, a five-compartment PK model including an enterohepatic re-circulation process was developed. For inhaled BUD, the incorporation of two parallel first-order absorption rate constants (fast and slow) for lung absorption in a two-compartment PK model emphasized the importance of pulmonary anatomical features and underlying physiological processes during model development. The role of potential covariates on the variability of the PK parameters was also investigated.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Drug Delivery Systems; Dry Powder Inhalers; Humans; Lung; Middle Aged; Models, Biological; Therapeutic Equivalency; 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

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

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94(0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen.. In asthma, overuse of beta-agonist reliever medication and delay in seeking medical review in an exacerbation are linked to asthma deaths. Janine Pilcher at the Medical Research Institute of New Zealand, and co-workers, conducted a review of data from a study of 303 adult patients with severe asthma, followed over 24 weeks. The patients were allocated to either a budesonide/formoterol, or a salbutamol inhaler to take for symptom relief, in addition to their maintenance treatment. Inhalers were fitted with electronic monitors, to accurately document every use. In both groups, on 90% of days when an exacerbation requiring excess use of an inhaler occurred, patients did not follow-up with medical professionals within 48 h as advised. Further, in both groups, 'extreme' reliever inhaler use was recorded at least once in around one in four patients.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Therapy, Combination; Female; Humans; Male; Nebulizers and Vaporizers; Prescription Drug Overuse; Treatment Outcome

To assess the level of asthma control achieved with budesonide/formoterol in Chinese patients with asthma, based on the Global Initiative for Asthma (GINA) definition and Asthma Control Test (ACT) score.. This multicenter, cross-sectional study (NCT01785901) evaluated asthma control levels in Chinese patients receiving physician-prescribed budesonide/formoterol treatment. Adults with a diagnosis of asthma ≥6 months and receiving budesonide/formoterol treatment ≥3 months before screening were consecutively enrolled. Data including medical and medication history were collected using face-to-face questionnaires and physical examinations during a single visit.. A total of 1483 asthma out-patients from 27 medical centers were enrolled; 217 (14.6%) were treated with budesonide/formoterol using a fixed-dose strategy and 1266 (85.4%) with the SMART (Symbicort. This study demonstrated high levels of asthma control (GINA: controlled and partly controlled and ACT: completely and well controlled) in Chinese patients with asthma treated with budesonide/formoterol. Greater age and a longer disease history were associated with lower levels of asthma control.. ClinicalTrials.govNCT01785901. Registered February 5, 2013.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; China; Cross-Sectional Studies; Female; Glucocorticoids; Humans; Male; Middle Aged

If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, addition of a long-acting β2 agonist (LABA) is the preferred treatment. Currently, there are several combinations of ICS/LABA that are available, each of which has a different property. Here, we aimed to compare the early effects of budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) with a fixed dose of fluticasone furoate/vilanterol (FF/VI; Relvar(®)).. Inadequately controlled asthma patients (defined as having an Asthma Control Questionnaire, 5-item version [ACQ5] score≥1.5) with a fractional exhaled nitric oxide (FeNO) value > 35 ppb, who had been treated with a medium dose of ICS alone, were enrolled. Patients were randomized into two groups and treated with two inhalations twice-daily of BUD/FM 160/4.5 μg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation once-daily of FF/VI 100/25 μg plus as-needed procaterol (FF/VI group, n = 15) for 4 weeks. Outcomes including FeNO, impulse oscillometry (IOS) parameters and ACQ5 scores were measured at 0, 2 and 4 weeks.. Both groups showed improvement in airway inflammation, pulmonary function and symptoms from baseline to 2 weeks. From 2 to 4 weeks, the SMART group exhibited continuous improvement in most measured parameters, whereas improvement in the FF/VI group seemed to reach a plateau transiently. Consequently, the SMART group showed significant improvement in the FeNO, IOS parameters (resonance frequency and integrated area of low frequency reactance) and ACQ5 score as compared with the FF/VI group at 4 weeks.. As compared with the FF/VI group, the SMART group achieved a greater improvement in FeNO, small airway parameters regarding IOS and ACQ score, in patients with airway inflammation and uncontrolled symptoms treated with a medium dose of ICS alone. In this 4-week study, these two ICS/LABA combination therapies showed different treatment outcomes; they must be investigated further to clarify suitable patient characters and the long term efficacies for each combination.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Drug Combinations; Female; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Surveys and Questionnaires; Time Factors; Treatment Outcome

Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count.. We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per μL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT01854047, and with the EU Clinical Trials Register, EudraCT number 2013-000856-16.. 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per μL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L [SE 0·05]; mean difference 0·21 [95% CI 0·06-0·36; p=0·0063]) and in the 200 mg group (mean change 0·43 L [SE 0·05]; mean difference 0·26 [0·11-0·40; p=0·0008]) compared with placebo (0·18 L [SE 0·05]). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per μL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per μL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70-70·5%), the subgroup with at least 300 eosinophils per μL (71·2-80·7%), and the subgroup with fewer than 300 eosinophils per μL (59·9-67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33-41% vs 35%) and injection-site reactions (13-26% vs 13%).. Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting β2-agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone.. Sanofi-Genzyme and Regeneron Pharmaceuticals.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Breath Tests; Budesonide, Formoterol Fumarate Drug Combination; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Injections, Subcutaneous; Male; Middle Aged; Mometasone Furoate, Formoterol Fumarate Drug Combination; Nitric Oxide; Treatment Outcome

Therapeutic equivalence of Budesonide/formoterol Easyhaler compared to Symbicort Turbuhaler has been previously demonstrated with in vitro and pharmacokinetic studies. This study was performed to confirm equivalent bronchodilator efficacy of the products in asthmatic patients.. A randomised, single-dose, 4-period crossover study was carried out in a double-blind, double-dummy manner in 11 study sites. The studied doses were 320/9 μg and 1280/36 μg of budesonide/formoterol delivered by Easyhaler and Turbuhaler. Spirometry was performed before and 10 min, 20 min and 1, 2, 3, 4, 6, 8, 10 and 12 h after administration of the study treatments. The primary efficacy endpoint was average 12-h forced expiratory volume in 1 s (FEV. 72 asthma patients with reversible airway obstruction were randomised to receive study treatments. 53 patients completed all study periods according to the protocol and had sufficient data available to calculate the primary endpoint. They were included in the per-protocol analyses. The assay sensitivity of the study was shown as the common slope of average 12-h FEV. The results confirm equivalent bronchodilator efficacy of Budesonide/formoterol Easyhaler compared to Symbicort Turbuhaler.. This trial was registered on ClinicalTrials.gov, Identifier: NCT02308098.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Bulgaria; Cross-Over Studies; Double-Blind Method; Dry Powder Inhalers; Ethanolamines; Female; Forced Expiratory Volume; Humans; Hungary; Male; Middle Aged; Nebulizers and Vaporizers; Spirometry; Treatment Outcome; Young Adult

A combination of the inhaled corticosteroid budesonide and the long-acting β2-agonist formoterol has been formulated in a novel dry powder inhaler, Spiromax(®). The objective was to compare lower leg growth in children with asthma treated with inhaled budesonide+formoterol (BF) delivered from the Spiromax inhaler with BF from the Symbicort Turbohaler(®).. Prepubescent children with persistent asthma (n=75, aged 6-11 years) were included in a randomized, double-blind, double-dummy, placebo-controlled, three-way crossover study with active treatment and placebo periods of 2 weeks duration. Lower leg length was measured every second week. As a secondary outcome parameter, 24-hr urine was collected for assessment of free cortisol. Interventions were dry powder BF 160+9 μg twice daily (b.i.d.; delivered dose) from the Spiromax inhaler and dry powder BF 200+12 μg b.i.d. (metered dose) from the Symbicort Turbohaler.. The least squares mean difference in lower leg growth rates (LLGR) between BF Spiromax and Symbicort Turbohaler was -0.086 mm/week [95% confidence interval (CI) -0.203, 0.032]. The pre-specified non-inferiority margin was -0.200 mm/week, so the lower limit of the 95% CI was just outside this margin. The difference between BF Spiromax and placebo was -0.20 mm/week (95% CI: -0.322, 0.086); p<0.001), between Symbicort Turbohaler and placebo -0.118 mm/week (95% CI: -0.236, -0.001; p=0.048). No statistically significant differences were seen in urine free cortisol assessments.. As the lower limit of the CI of LLGR was marginally outside of the pre-specified non-inferiority margin between BF Spiromax 160+9 μg b.i.d. and Symbicort Turbohaler 200+12 μg b.i.d., non-inferiority could not be demonstrated. Further studies may be needed for comparison of systemic activity of BF Spiromax and Symbicort Turbohaler in children before firm conclusions about their comparability may be drawn.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Glands; Adrenergic beta-2 Receptor Agonists; Age Factors; Anthropometry; Asthma; Biomarkers; Budesonide, Formoterol Fumarate Drug Combination; Child; Cross-Over Studies; Denmark; Double-Blind Method; Dry Powder Inhalers; Female; Humans; Hydrocortisone; Least-Squares Analysis; Leg; Lung; Male; Risk Factors; Sexual Development; Time Factors; Treatment Outcome

Asthma is a chronic inflammatory airway disease of the whole bronchial tree. In this exploratory study we investigated the effects of beclomethasone/formoterol (becl/form) and budesonide/formoterol (bud/form) fixed combinations on lung function and airway inflammation in patients with mild to moderate asthma.. 22 adult patients with asthma (mean FEV1 91.6% pred.) were recruited to this prospective phase IV, double-blind, double-dummy, two-way cross-over, single-centre, randomised study. After a 7 days run-in period with bud 200 μg bid patients were randomised to receive 4 weeks of becl/form (100/6 μg) bid in a pressurised metered dose inhaler or bud/form (160/4.5 μg) bid administered via dry powder inhaler. We measured spirometry, bodyplethysmography, impulse oscillometry, nitric oxide (NO) and its alveolar fraction (CAlv), and assessed sputum cellularity.. CAlv significantly decreased after 4 weeks of treatment in each treatment period. The adjusted geometric mean (log transformed data, end of treatment vs. baseline) was 0.942 ppb (95% CI: 0.778-1.141 ppb) for becl/form and 0.903 ppb (95% CI: 0.741-1.099 ppb) for bud/form. Impulse oscillometry revealed a significant decrease in mean Delta R5-R20 of -0.033 kPa * L(-1) * sec(-1) for becl/form (95% CI: -0.064 to -0.002) and of -0.048 033 kPa * L(-1) * sec(-1) for bud/form (95% CI: -0.079 to -0.017). Other parameters of lung function and NO showed numerically small and in most cases statistically non-significant changes.. In patients with mild to moderate asthma pre-treated with inhaled corticosteroids, the use of ICS/LABA formulations led to improvements of CAlv and Delta R5-R20 indicating that these parameters might be helpful to further assess the effects of inhaled ICS/LABA combinations on lung function and airway inflammation.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide, Formoterol Fumarate Drug Combination; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Formoterol Fumarate; Humans; Inflammation; Male; Patient Compliance; Prospective Studies; Respiratory Function Tests; Severity of Illness Index; Sputum

The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real-life effectiveness are seldom reported.. This multicenter trial enrolled steroid-naïve, symptomatic asthmatics with baseline exhaled nitric oxide (eNO) of ≥ 40 ppb. There were 120 eligible patients who were randomized and received a dose of inhaled budesonide/formoterol 320/9 μg (lower dose budesonide/formoterol), 640/18 μg (higher dose budesonide/formoterol (HDBF)), or terbutaline (TERB) 1 mg. Inflammatory cells and mediators in induced sputum, eNO and lung function were measured at baseline and 6 h (acute phase). Subsequently, all patients used BFMRT as real-life practice for 24 weeks (maintenance phase).. In the acute phase, the degree of post-treatment reduction in total eosinophil counts, interleukin-8 and matrix metalloproteinase-9 in induced sputum were significantly greater in group HDBF (vs TERB, P < 0.05). The increase in forced expiratory volume in first second (FEV1 ) in group HDBF was significantly higher (vs LDBF and TERB, P < 0.05) 3 h after dosing. In the maintenance phase, significant improvement of asthma control (presented by eNO, FEV1 and a five-item asthma control questionnaire) in real-life settings was observed at 4 weeks and sustained to the end of study. The rate of patients who followed scheduled visits declined over time (87% at week 4 and 42% at week 24).. Budesonide/formoterol as reliever exerts acute, dose-related anti-inflammatory effects and FEV1 improvement in symptomatic asthmatics. BFMRT is effective in asthma control. However, the decrease in long-term follow-up rate remains an issue to overcome in real-life settings.

Topics: Administration, Inhalation; Adult; Asthma; Breath Tests; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Cell Count; Drug Combinations; Eosinophils; Ethanolamines; Exhalation; Female; Forced Expiratory Volume; Humans; Interleukin-8; Maintenance Chemotherapy; Male; Matrix Metalloproteinase 9; Middle Aged; Nitric Oxide; Sputum; Terbutaline; Vital Capacity; Young Adult

Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting β2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma.. In this non-inferiority randomised clinical trial, we recruited adult patients (18-65 years of age) with stable moderate persistent asthma, according to 2006 Global Initiative for Asthma guidelines. Patients were recruited from outpatient clinics of secondary and tertiary referral hospitals and university centres. After a 6-week run-in period of inhaled regular budesonide and formoterol plus as-needed terbutaline, the patients were randomly assigned in a 1:1 ratio to receive placebo twice daily plus as-needed treatment with inhaled 160 μg budesonide and 4·5 μg formoterol (as-needed budesonide and formoterol therapy) or twice-daily 160 μg budesonide and 4·5 μg formoterol combination plus symptom-driven 500 μg terbutaline (regular budesonide/formoterol therapy) for 1 year. Randomisation was done according to a list prepared with the use of a random number generator and a balanced-block design stratified by centre. Patients and investigators were masked to treatment assignment. The primary outcome was time to first treatment failure measured after 1 year of treatment using Kaplan-Meier estimates, and the power of the study was calculated based on the rate of treatment failure. Analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00849095.. Between April 20, 2009, and March 31, 2012, we screened 1010 patients with moderate asthma and randomly assigned 866 eligible patients to the two treatment groups (424 to as-needed budesonide and formoterol therapy and 442 to regular budenoside and formoterol therapy). Compared with regular budesonide and formoterol therapy, as-needed budesonide and formoterol treatment was associated with a lower probability of patients having no treatment failure at 1 year (Kaplan-Meier estimates 53·6% for as-needed treatment vs 64·0% for regular treatment; difference 10·3% [95% CI 3·2-17·4], at a predefined non-inferiority limit of 9%). Patients in the as-needed budesonide and formoterol group had shorter time to first treatment failure than those in the regular therapy group (11·86 weeks vs 28·00 weeks for the first quartile [ie, the time until the first 25% of patients experienced treatment failure]). The difference in treatment failures was largely attributable to nocturnal awakenings (82 patients in the as-needed treatment group vs 44 in the regular treatment group). Both treatment regimens were well tolerated.. In patients with moderate stable asthma, as-needed budesonide and formoterol therapy is less effective than is the guideline-recommended regular budesonide and formoterol treatment, even though the differences are small.. Italian Medicines Agency.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Terbutaline; Treatment Failure; Young Adult

Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation.. This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device.. After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training.. The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Child; Cross-Over Studies; Dry Powder Inhalers; Equipment Design; Female; Healthy Volunteers; Humans; Inhalation; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Young Adult

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

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

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In June 2020, the New Zealand (NZ) adolescent and adult asthma guidelines recommended budesonide/formoterol, taken as maintenance and/or reliever therapy, as the preferred therapeutic approach.. To investigate whether these recommendations were associated with changes in clinical practice indicated by asthma medication use trends.. NZ national dispensing data for inhaler medications from January 2010 to December 2021 were reviewed. Monthly "dispensings" of inhaled budesonide/formoterol, inhaled corticosteroid (ICS), other ICS/long-acting β. Budesonide/formoterol dispensing increased markedly after July 1, 2020 (regression coefficient 41.1 inhalers dispensed/100,000 population per month [95% confidence interval (CI): 36.3-45.6, P < .0001]; 64.7% increase in the number of dispensings between July-December 2019 and July-December 2021), in contrast to "other ICS/LABA" (regression coefficient: -15.9 [95% CI: -22.2 to -9.6, P < .0001]; -1.7% decrease) and SABA (regression coefficient: -14.7 [95% CI: -29.7 to 0.3, P = .055]; -10.6% decrease), respectively.. In NZ, a progressive increase in budesonide/formoterol dispensing, accompanied by a reduction in SABA and "other ICS/LABA" dispensing, occurred after publication of the 2020 NZ asthma guidelines. While acknowledging the limitations in the interpretation of temporal associations, these findings suggest that the transition to ICS/formoterol reliever-based therapy can be achieved if recommended and promoted as the preferred therapeutic approach in national guidelines.

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

The Global Initiative for Asthma and National Asthma Education and Prevention Program recently made paradigm-shifting recommendations regarding inhaler management in asthma. The Global Initiative for Asthma now recommends that combination inhaled corticosteroid (ICS)-formoterol inhalers replace short-acting β-agonists as the preferred reliever therapy at all steps of asthma management. Although the most recent guidelines of the National Asthma Education and Prevention Program did not review reliever ICS-formoterol usage in mild asthma, they similarly recommended single maintenance and reliever therapy (SMART) at steps 3 and 4 of asthma management. Despite these recommendations, many clinicians-particularly in the United States-are not prescribing new inhaler paradigms. Clinician-level reasons for this implementation gap remain largely unexplored.. To gain an in-depth understanding of the facilitators and barriers to prescribing reliever ICS-formoterol inhalers and SMART in the United States.. Community and academic primary care providers, pulmonologists, and allergists who reported regularly caring for adults with asthma were interviewed. Interviews were recorded, transcribed, qualitatively coded, and analyzed using the Consolidated Framework for Implementation Research. Interviews were continued until theme saturation.. Among 20 interviewed clinicians, only 6 clinicians described regularly prescribing ICS-formoterol inhalers as a reliever inhaler (either alone or within SMART). Significant barriers to new inhaler approaches included concerns surrounding a lack of Food and Drug Administration labeling for ICS-formoterol as a reliever therapy, a lack of awareness regarding a patient's formulary-preferred ICS-long-acting β-agonist choices, the high cost of combination inhalers, and time constraints. Facilitators to using new inhaler approaches included clinicians' beliefs that the latest inhaler recommendations are simpler and more congruent with real-world patients' behavior, and that a potential change in management strategy would offer a valuable opportunity for shared decision making.. Although new guidelines exist in asthma, many clinicians described significant barriers to using them including medicolegal issues, pharmaceutical formulary confusion, and high drug costs. Nonetheless, most clinicians believed that the latest inhaler approaches would be more intuitive for their patients and would offer an opportunity for patient-centered collaboration and care. Stakeholders may find these results useful in future attempts to increase the real-world adoption of recent asthma recommendations.

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

Recent data indicate that overuse of short-acting beta2-agonists (SABAs) results in an increased risk of asthma exacerbations and mortality. The use of inhaled corticosteroid-formoterol as both maintenance and reliever therapy has become a preferred regimen for asthma management. Clinicians should be aware of the pharmacology, dosing, and prescribing considerations regarding the use of budesonide-formoterol as the available combination in the United States.

Topics: Asthma; Budesonide, Formoterol Fumarate Drug Combination; Formoterol Fumarate; Humans; Patients

The study aims to compare the real-world effectiveness and economy of the budesonide/formoterol reliever and maintenance therapy (SMART) with fixed-dose inhaled corticosteroids (ICS)/long-acting b-agonist (LABA) or ICS alone plus as-needed, short-acting β2 agonists (SABA) in pediatric patients.. The outpatient data warehouse of a hospital in China was used. A total of 103 patients under 18 years old in the SMART group and 63 patients in the control group were included from January 1, 2020 to December 31, 2021. The effectiveness was assessed using asthma attacks and lung function at baseline, 6 months and 12 months follow-up. Cost-effectiveness analysis was performed with a three-state Markov model from the healthcare system perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to check the robustness of the results.. The SMART regimen was more effective than other strategies in reducing the risk of mild and severe attacks in the real-life management of childhood asthma. Patients in both groups showed significant improvement in lung function at 6 and 12 months in contrast to baseline. Compared with other strategies, the forced expiratory volume in 1 s (FEV. Collectively, our findings indicate that the real-world effectiveness and economy of the SMART regimen are superior to the traditional strategies in pediatric asthma patients.

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

A heavy financial burden is imposed on patients suffering from chronic diseases due to medicine out-of-pocket payments.. This study focuses on assessing the affordability of medications used for chronic respiratory diseases (CRDs) such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) in Iran, specifically on the category R medicines listed in the 2017 Iran drug list (IDL) that are used for the treatment of these diseases, based on the anatomical therapeutic chemical (ATC) drug code.. The affordability of medicines in mono and combination therapy approaches was assessed in CRDs using the World Health Organization/Health Action International (WHO/HAI) methodology. Accordingly, if out-of-pocket payment for 30-days of pharmacotherapy exceeds one day for the lowest-paid unskilled government worker (LPGW), it's considered non-affordable.. Based on the monotherapy approach, our finding demonstrates that all generic medicines of category R were affordable. However, branded drugs such as Symbicort®, Pulmicort Respules®, Flusalmex®, Seretide®, Fluticort Plus®, Seroflo®, and Salmeflo® cost between 1.2 and 2.5 days' wage of LPGW and considered unaffordable despite 70% insurance coverage. Moreover, based on the affordability ratio in the combination therapy approach, all medicines used in asthma, COPD, and CF patients with mild respiratory problems are affordable except omalizumab (inj), which is non-affordable due to its high price and no insurance coverage.. Results showed that the existing insurance coverage does not protect households from hardship, so more considerations are needed such as different insurance schedules and patient support programs.

Topics: Asthma; Budesonide, Formoterol Fumarate Drug Combination; Costs and Cost Analysis; Cystic Fibrosis; Health Services Accessibility; Humans; Pulmonary Disease, Chronic Obstructive

Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.. To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.. Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations.. Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications.. Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Humans; National Health Programs

To determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.. Retrospective observational study conducted by review of electronic medical records (database: Fundación RediSS).. Retrospective cohort study. The follow-up period was 1 year.. The study included patients aged ≥18 years who started treatment with ICS/LABA and met the inclusion/exclusion criteria.. The study groups were fluticasone propionate/salmeterol (FP/SAL), beclomethasone/formoterol (BDP/FORM), budesonide/formoterol (BUD/FORM), fluticasone furoate/vilanterol (FF/VI) and fluticasone propionate/formoterol (FP/FORM). The main measurements were persistence, medication possession ratio (MPR) and exacerbations. Statistical significance was established as p<0.05.. In total, 3203 patients were recruited for the study. By groups, 31.1% FP/SAL, 28.6% BDP/FORM, 25.0% BUD/FORM, 8.2% FF/VI and 7.0% FP/FORM. The mean age was 52.2 years, 60.8% were female and 44.9% had persistent-moderate asthma. Treatment persistence was 61.7% (95% CI 60.0% to 63.4%) and by study group it was FP/SAL: 60.7%, BDP/FORM: 61.2%, BUD/FORM: 60.3%, FF/VI: 66.7% and FP/FORM: 67.6% (p=0.046). MPR by study group was FP/SAL: 74.3%, BDP/FORM: 73.8%, BUD/FORM: 74.6%, FF/VI: 79.4% and FP/FORM: 80.6% (p=0.028). The mortality rate was 2.9%. By treatment group, exacerbations were FP/SAL: 21.9% (95% CI 19.3% to 24.5%), BDP/FORM: 22.2% (95% CI 19.5% to 24.9%), BUD/FORM: 22.8% (95% CI 19.9% to 25.7%), FF/VI: 17.9% (95% CI 14.9% to 20.7%) and FP/FORM: 16.0% (95% CI 12.2% to 19.3%), p=0.036.. Patients undergoing treatment with FP/FORM and FF/VI versus FP/SAL, BDP/FORM and BUD/FORM were associated with greater treatment adherence (persistence, MPR) and lower rates of exacerbations. However, further studies will be needed to strengthen the consistency of the results.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Retrospective Studies

Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important.. We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up.. Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups.. Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence.. 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).

Topics: Adult; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Prospective Studies; Quality of Life; Treatment Outcome

In randomised controlled trials, as-needed inhaled corticosteroid (ICS)-formoterol reliever therapy reduces severe exacerbation risk compared with maintenance ICS plus short-acting beta. To assess the levels and changes in asthma control for as-needed budesonide-formoterol versus maintenance budesonide plus SABA in post hoc analyses from the Novel START and PRACTICAL clinical trials.. The number and proportion of participants at study end in each ACQ-5 category ('well-controlled', 'partly controlled' or 'inadequately controlled' symptoms), and in each responder category based on the minimal clinically important difference for ACQ-5 of 0.5 (improved, no change and worse) with as-needed budesonide-formoterol and maintenance budesonide plus SABA treatment were calculated.. With last observation carried forwards, 189/214 (88.3%) and 354/434 (81.6%) of patients in the budesonide-formoterol group had 'well-controlled' or 'partly controlled' symptoms at the end of the study, vs 183/214 (85.5%) and 358/431 (83.1%) in the budesonide maintenance group, for Novel START and PRACTICAL, respectively. The proportion of patients whose symptom control was either improved or unchanged from baseline was 190/214 (88.8%) and 368/434 (84.8%) for budesonide-formoterol, vs 185/214 (86.4%) and 376/431 (87.2%) for maintenance budesonide, in Novel START and PRACTICAL respectively.. There were no clinically important differences in the proportions of patients with 'well-controlled' or 'partly controlled' asthma symptoms, or proportions who improved or maintained their level of control, with as-needed budesonide-formoterol versus maintenance budesonide plus SABA.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic

This is a retrospective, descriptive study of linked primary and secondary healthcare data (Clinical Practice Research Datalink Aurum, Hospital Episode Statistics). Patients with COPD were indexed on first prescription of fixed-dose, single-device ICS/LABA (June 2015-December 2018). Demographics, clinical characteristics, prescribed treatments, healthcare resource use (HCRU) and direct healthcare costs were assessed over 12 months pre-index. Incident users (indexed on first ever prescription) could be non-triple users (no concomitant long-acting muscarinic antagonist at index); a subset were initial maintenance therapy (IMT) users (no history of pre-index maintenance therapy).. Overall, 13 451 incident users (non-triple users: 7448, 55.4%; IMT users: 5162, 38.4%) were indexed on beclomethasone dipropionate/formoterol (6122, 45.5%), budesonide/formoterol (2703, 20.1%) or Other ICS/LABA combinations (4626, 34.4%). Overall, 20.8% of incident users had comorbid asthma and 42.6% had ≥1 moderate-to-severe acute exacerbation of COPD pre-index. Baseline characteristics were similar across indexed therapies. At 3 months pre-index, 45.3% and 35.4% of non-triple and IMT users were receiving maintenance treatment. HCRU and direct healthcare costs were similar across indexed treatments. Prescribing patterns varied regionally.. Patient characteristics, prior treatments, prior COPD-related HCRU and direct healthcare costs were similar across single-device ICS/LABAs in primary care in England. A high proportion of patients were not receiving any respiratory medication pre-index, indicating that prescribing in primary care in England is more closely aligned with national guidelines than global treatment strategies. Comorbid asthma may have influenced prescribing decisions. Less than half of users had preindex exacerbations, suggesting that ICS/LABA is not being prescribed principally based on exacerbation history.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Beclomethasone; Budesonide, Formoterol Fumarate Drug Combination; Formoterol Fumarate; Humans; Muscarinic Antagonists; Primary Health Care; Pulmonary Disease, Chronic Obstructive; Retrospective Studies

To evaluate the budgetary impact of using budesonide + formoterol (Symbicort Turbuhaler) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma with the drug salmeterol + fluticasone and salbutamol on demand.. A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort Turbuhaler) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results.. Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort Turbuhaler) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort Turbuhaler) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort Turbuhaler) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years.. Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort Turbuhaler) will reduce the financial burden on both the healthcare system and the budgetary system.. Цель. Оценить влияние препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) на бюджет при его применении в качестве поддерживающей терапии в реальной клинической практике в сравнении со стандартной терапией при бронхиальной астме (БА) различной степени тяжести: для БА легкого течения с сальбутамолом по требованию, для БА среднетяжелого и тяжелого течения с препаратом салметерол + флутиказон и сальбутамолом по требованию. Материалы и методы. Построена статическая математическая модель для оценки влияния лекарственного препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) в лечении БА на бюджет при внедрении его в клиническую практику с точки зрения государства. Демографические данные взяты из официальных данных Федеральной службы государственной статистики. Прямые медицинские затраты включали расходы на лекарственные средства, затраты на госпитализацию пациентов, сопряженную с развитием обострений БА, и затраты на плановые амбулаторные визиты. Косвенные затраты учитывали потерю ВВП в связи с госпитализацией пациентов на фоне обострений БА. Односторонний анализ чувствительности провели для подтверждения надежности результатов исследования. Результаты. Оценка прямых затрат при лечении БА легкого, среднетяжелого и тяжелого течения показала, что постепенное увеличение доли пациентов, получающих препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), в 1, 2, 3-й год приема до 5,5, 7,7 и 9,7% соответственно, привело к возрастанию затрат на фармакотерапию за это время на 1,7 млрд руб., при том что прямые нелекарственные затраты, связанные с лечением осложнений, развившихся на фоне лечения БА, уменьшились на 8,3 млрд руб. Таким образом, снижение суммарных прямых затрат составило 6,7 млрд руб. Косвенные затраты при этом сократились на 6,0 млрд руб. Общее снижение всех затрат (прямых и косвенных) при переключении пациентов на будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) составило 12,5 млрд руб. Кроме того, препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) помог снизить число обострений: в 1-й год на 3137, во 2-й на 4393 и в 3-й на 5534 случая. Суммарно за 3 года было предотвращено 13 064 обострения БА. Заключение. Увеличение доли пациентов с БА различной степени тяжести, получающих терапию с препаратом будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), позволит снизить финансовую нагрузку как на систему здравоохранения, так и на бюджетную систему государства в

Topics: Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Delivery of Health Care; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans

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

In mild asthma, as-needed budesonide-formoterol offers similar protection from severe exacerbations as daily inhaled corticosteroids (ICS), with lower ICS exposure but slightly increased symptoms. We sought to develop an electronic decision aid to guide discussions about the pros and cons of these first-line options, while identifying and integrating user preferences.. Following International Patient Decision Aid Standards, we created a mild asthma decision aid prototype comparing convenience, clinical outcomes, cumulative ICS dose exposure, costs, and side-effects of each option. After face validation, the prototype was iteratively adapted through rapid-cycle development. Each cycle consisted of a patient focus group and a primary care physician interview. We made user preference-based improvements after each round, until reaching a pre-set stopping criterion (no new critical issues identified). We then performed a summative qualitative content analysis.. Over 5 cycles, we recruited 21 asthma patients (12/21 women, 10/21 ≥ 60 years old) and 5 physicians. Serial changes included simplification and reduction of text and reading level, inclusion of an ICS "myths" section and elaboration of patient-friendly infographics for numerical comparisons. User preferences fell within Content, Format, and tool use Process themes. In response to decision-making preferences, we created a complementary one-page conversation aid for patient-provider use at the point-of-care.. We present preference-based electronic patient decision and conversation aids for treatment of mild asthma. Our user preference analyses offer useful insights for development of such tools in other chronic diseases. These tools now require integration into point-of-care workflows for measurement of real-world uptake and impact.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Decision Support Techniques; Female; Humans; Middle Aged

Previously evidence has demonstrated that as-needed combination low-dose budesonide-formoterol reduced the risk of severe exacerbations compared with short-acting β2-agonist (SABA) reliever therapy in an adolescent with mild asthma. Concerns as if the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) reliever therapy in adolescents with mild asthma in Colombia.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. The model suggests a potential gain of 0.03 QALYs and per patient per year on low-dose budesonide-formoterol. The cost difference per person was US$-4 per patient per year in favor of budesonide- formoterol. The position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the one-way and probabilistic sensitivity analyses, our base-case results were robust to variations of all assumptions and parameters.. In conclusion, low-dose budesonide-formoterol as a reliever was found to be cost-effective when added to usual care in adolescents with mild asthma. This evidence should promote economic evaluations in developed and developing countries for the inclusion of new drugs in health insurance plans.

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

Topics: Adolescent; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Humans; Lung

Topics: Adolescent; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Humans; Lung

Recent asthma guidelines, such as the Global Initiative for Asthma (GINA), recommend in adult patients as-needed inhaled corticosteroids (ICS)-formoterol as an alternative to maintenance ICS in mild to moderate persistent asthma. The introduction of these recommendations concerns whether using as-needed budesonide-formoterol would be more cost-effective than to maintenance ICS. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) reliever therapy in patients with mild asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared to short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. The model suggests a potential gain of 0.37 QALYs and per patient per year on as-needed ICS-formoterol and a reduction in the discounted cost per person-year, of as-needed ICS-formoterol to maintenance ICS, of US$40. This position of dominance of as-needed ICS-formoterol negates the need to calculate an incremental cost-effectiveness ratio. In the deterministic and probabilistic sensitivity analysis, our base-case results were robust to variations in all assumptions and parameters.. Low-dose budesonide-formoterol as a reliever was cost-effective when added to usual care in patients with mild asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Colombia; Cost-Benefit Analysis; Humans; Markov Chains; Models, Econometric; Nebulizers and Vaporizers; Quality-Adjusted Life Years

Topics: Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Female; Humans; Male; Nebulizers and Vaporizers

Previous studies have found suboptimal control of symptom burden to be widespread among patients with asthma and chronic obstructive pulmonary disease (COPD). The Phase IV SPRINT study was conducted in 10 countries in Europe to assess asthma disease control and COPD symptom burden in patients treated with a fixed-dose combination (FDC) of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). SPRINT included 1101 patients with asthma and 560 with COPD; all were receiving treatment with an FDC of ICS/LABA, delivered via various inhalers. Data were obtained over a 3-month period, during a single routine physician's office visit. Asthma control was defined as Asthma Control Test (ACT) score >19. COPD symptom burden was assessed by COPD Assessment Test (CAT), with a CAT score <10 defining low COPD symptom burden. Among patients using any ICS/LABA FDC, 62% of patients with asthma had achieved disease control (ACT score >19) and 16% of patients with COPD had low symptom burden (CAT score <10).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dry Powder Inhalers; Europe; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Treatment Outcome

A retrospective new-user active comparator database study was conducted in the IQVIA Medical Research Database. Propensity score (PS) matching was performed for FF/VI versus BUD/FM, and FF/VI versus BDP/FM. The primary objective was to compare patient treatment persistence (time to discontinuation), while secondary objectives included assessing adherence (mean proportion of days covered [PDC] with medication in the study period) and the proportions of patients achieving ≥ 50% and ≥ 80% PDC.. New users of FF/VI (N = 966), BUD/FM (N = 5931) and BDP/FM (N = 9607) were identified and PS-matched: FF/VI (n = 945) versus BUD/FM (n = 3272), and FF/VI (n = 902) versus BDP/FM (n = 3465). At 12 months, treatment persistence was 69% (FF/VI), 53% (BUD/FM) and 57% (BDP/FM). The likelihood of treatment discontinuation within 12 months after initiation with FF/VI was 35% lower than with BUD/FM and 31% lower than for BDP/FM (both p < 0.001). Mean PDC was higher for FF/VI compared with BUD/FM (77.7 vs 72.4; p < 0.0001) and BDP/FM (78.2 vs 71.0; p < 0.0001). The odds of achieving ≥ 50% and ≥ 80% PDC were greater for FF/VI than for BUD/FM and BDP/FM.. In this study, patients who initiated FF/VI were less likely to discontinue treatment and showed greater treatment adherence versus patients who initiated BUD/FM or BDP/FM.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Benzyl Alcohols; Budesonide, Formoterol Fumarate Drug Combination; Child; Chlorobenzenes; Cohort Studies; Female; Humans; Male; Medication Adherence; Middle Aged; Retrospective Studies; United Kingdom; Young Adult

As-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting β2-agonist (SABA).. A probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 μg or twice-daily budesonide 200 μg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses.. On average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates.. From a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Child; Cost-Benefit Analysis; Female; Humans; Maintenance Chemotherapy; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; United Kingdom; Young Adult

Combination low-dose budesonide-formoterol, taken as-needed for symptom relief reduces exacerbation risk and is recommended for treatment of mild asthma. The NovelQ qualitative study explored patients' attitudes toward using this novel therapy.. Adults with mild asthma using reliever-only treatment were randomised to as-needed budesonide-formoterol Turbuhaler® in a multinational, 52-week open-label randomised controlled trial (NovelSTART-ACTRN12615000999538). A subgroup were interviewed to explore their attitudes to use of as-needed budesonide-formoterol after receiving it for ≥10 months. Semi-structured interviews were conducted until saturation, audio-recorded, and thematically analysed.. Analysis of 35 participants (66% female; mean age 43.5 [range 18-74]; mean Asthma Control Questionnaire score 1.09 ± SD0.55) interviews identified 5 themes, each including both barriers and facilitators to therapy use. Themes were: 'Treatment effectiveness' i.e. how well symptoms were relieved and/or prevented; 'Lifestyle fit of the regimen' e.g. the extent to which the treatment regimen integrated into the patient's daily life; 'Attitudes toward medication use and safety' e.g. openness for new reliever treatments, beliefs about treatment necessity or side effects; 'Device attributes' e.g. perceived ease of use; and 'Doctor-patient relationship' e.g. impact of health professional support on new treatment acceptance.. A wide range of factors seem to drive the opinions of mild asthma patients on as-needed budesonide-formoterol therapy. Many patients perceived both positive and negative treatment attributes, and their individual evaluation of these attributes determined their likelihood of using it after the study. Supportive patient-physician interactions appear key to addressing patient barriers. Recommendations for patient-centred discussions, developed from this research, are provided.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Attitude to Health; Budesonide, Formoterol Fumarate Drug Combination; Female; Humans; Male; Medication Adherence; Middle Aged; Nebulizers and Vaporizers; Patient Preference; Physician-Patient Relations; Qualitative Research; Randomized Controlled Trials as Topic; Severity of Illness Index; Young Adult

Topics: Administration, Inhalation; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dry Powder Inhalers; Europe; Female; Humans; Medication Adherence; Middle Aged; Patient Satisfaction; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment.. Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 μg twice daily + budesonide/formoterol 200/6 μg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction.. Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction.. Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

Topics: Adult; Airway Obstruction; Airway Remodeling; Anti-Asthmatic Agents; Asthma; Bronchi; Budesonide, Formoterol Fumarate Drug Combination; Female; Humans; Inflammation; Male; Middle Aged; Prednisone

Data on inhaler technique and its effects on maternal and fetal outcomes during pregnancy are seldom reported. The primary objective of this study was to evaluate inhaler technique and identify errors in inhaler use among pregnant women with asthma. Secondary objectives were to identify factors associated with poor inhaler technique and study the association between inhaler technique and maternal and fetal outcomes. This was a cross-sectional, face-to-face, prospective study of 80 pregnant women with physician-diagnosed asthma. Seventy-three and 41 asthmatic pregnant women reported using pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), respectively. Overall, wrong inhaler technique was observed in 47 (64.4%) subjects. Among pMDI users, correct inhaler use was observed in only 26/73 (35.6%) of the patients, with lack of coordination between inhalation and generation of the aerosol and failure to breathe out gently before using the inhaler, being the most common errors. Among DPI users, 21 (51.2%) demonstrated correct inhaler use, with failure to perform a breath-hold for 10 seconds after inhaling the powder and to exhale gently before using the inhaler being the most common errors. Significant associations between inhaler technique and patient's understanding of asthma medications and the kind of follow-up clinic (respiratory versus nonrespiratory clinic) were found. No significant associations between inhaler technique and various maternal and fetal outcomes or asthma control were found. In conclusion, improper inhalation technique is significantly prevalent in pregnant asthmatic women, particularly among those being followed in nonspecialized respiratory clinics. The lack of significant association between the inhaler technique and asthma control (and hence maternal and fetal outcomes) may simply reflect the high prevalence of uncontrolled asthma and significant contribution of other barriers to poor asthma control in the current patient's cohort. Multidisciplinary management of asthma during pregnancy with particular emphasis on patient's education is imperative.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cesarean Section; Congenital Abnormalities; Cross-Sectional Studies; Disease Progression; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Humans; Infant, Low Birth Weight; Infant, Newborn; Metered Dose Inhalers; Patient Medication Knowledge; Pregnancy; Pregnancy Complications; Prospective Studies; Qatar; Respiratory Distress Syndrome, Newborn

Fixed-dose combinations of inhaled corticosteroids and long-acting β. A model was developed to estimate the budget impact of reducing poor inhalation technique by switching asthma and COPD patients from BF Turbuhaler. In Scenario 1, per patient cost savings amounted to €60.10, €49.67, €94.14 and €38.20 in Germany, Italy, Sweden and the UK, respectively. Total cost savings in each country were €100.86 million, €19.42 million, €36.65 million and €15.44 million over three years, respectively, with an estimated 597,754, 151,480, 228,986 and 122,368 healthcare events avoided. In Scenario 2, cost savings totalled €8.07 million, €1.55 million, €2.93 million and €1.23 million over three years, respectively, with 47,850, 12,118, 18,319, and 9789 healthcare events avoided. Savings per patient were €4.81, €3.97, €7.53 and €3.06.. We demonstrated that reductions in poor inhalation technique by switching patients from BF Turbuhaler

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dry Powder Inhalers; Formoterol Fumarate; Germany; Glucocorticoids; Health Care Costs; Humans; Italy; Pulmonary Disease, Chronic Obstructive; Sweden

Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.. Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days' wages it would cost the least paid public servant were analysed.. The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for formoterol/budesonide inhalers and 27.8 days' wages for spirometry.. Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Diagnostic Techniques, Respiratory System; Drug Combinations; Drug Costs; Fluticasone-Salmeterol Drug Combination; Health Services Accessibility; Humans; Leukotriene Antagonists; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; Uganda

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Delayed-Action Preparations; Dose-Response Relationship, Drug; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Nebulizers and Vaporizers; Treatment Outcome

Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at -0 °C. Delivered dose (DD) and fine-particle dose (FPD) were tested in vitro before and after storage. BUD inhalers: Turbuhaler and Novolizer showed only small decreases (<15%) in FPD in 40 °C/75% RH, whereas FPD for Easyhaler decreased by >60% (P=0.01) after 1.5 months of storage. Easyhaler also decreased significantly after 6 months of storage in ambient/75%RH by 25% and 54% for DD and FPD, respectively, whereas only small decreases were seen for Turbuhaler and Novolizer (<15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 °C/75% RH, whereas Easyhaler showed a small decrease. FPD (budesonide) decreased for Turbuhaler, Spiromax and Easyhaler by 18%, 10% and 68% (all significant), respectively, at 40 °C/75% RH. In ambient/75%RH, DD was unchanged for all inhalers, whereas FPD (budesonide) decreased for Spiromax (7%, P=0.02) and Easyhaler (34%, (P<0.01)). There are significant differences in device performance after exposure to humid conditions. A clinically relevant decrease of more than half FPD was seen for one of the inhalers, a decrease that may affect patients' clinical outcomes. Prescriber and patient knowledge on device attributes are essential to ensure optimal drug delivery to the lungs.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Dry Powder Inhalers; Humans; Humidity; In Vitro Techniques; Pulmonary Disease, Chronic Obstructive

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Female; Humans; Male; Terbutaline

After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany.. Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses.. Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of "concomitant LABA and ICS users" increased from 52.0 to 57.6% within the study period, whereas for "LABA users without ICS" a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present.. Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Beclomethasone; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Drug Combinations; Drug Therapy, Combination; Drug Utilization Review; Female; Fluticasone-Salmeterol Drug Combination; Germany; Glucocorticoids; Guideline Adherence; Humans; Male; Middle Aged; Mometasone Furoate; Practice Guidelines as Topic; Practice Patterns, Physicians'; Salmeterol Xinafoate; Young Adult

Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is associated with rapid decline in lung function, poorer health-related quality-of-life outcomes, and frequent exacerbations, compared to COPD alone. Although the numbers of patients with ACOS have increased, there is little established evidence regarding diagnostic criteria and treatment options. Thus, the aim of our study was to clarify the clinical, physiological, and radiological features of patients with ACOS.. We examined a total of 100 patients with COPD and 40 patients with ACOS, who were selected based on clinical criteria. All patients underwent baseline testing, including a COPD assessment test, pulmonary function tests, and multidetector row computed tomography imaging. Percentage of low attenuation volume, percentage of wall area, and percentage of total cross-sectional area of pulmonary vessels less than 5 mm(2) (%CSA <5) were determined using multidetector row computed tomography. ACOS patients were administered a fixed dose of budesonide/formoterol (160/4.5 μg, two inhalations; twice daily) for 12 weeks, after which the ACOS patients underwent multidetector row computed tomography to measure the same parameters.. At baseline, the ACOS patients and COPD patients had a similar degree of airflow limitation, vital capacity, and residual volume. ACOS patients had higher COPD assessment test scores, percentage of wall area, and %CSA <5 than COPD patients. Compared to baseline, budesonide/formoterol treatment significantly increased the forced expiratory volume in 1 second and decreased the degree of airway wall thickness (percentage of wall area) as well as pulmonary microvascular density (%CSA <5) in ACOS patients.. Our results suggest that ACOS is characterized by an airway lesion-dominant phenotype, in contrast to COPD. Higher %CSA <5 might be a characteristic feature of ACOS.

Topics: Administration, Inhalation; Aged; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Drug Administration Schedule; Female; Humans; Lung; Male; Middle Aged; Multidetector Computed Tomography; Phenotype; Predictive Value of Tests; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Veins; Recovery of Function; Respiratory Function Tests; Syndrome; Time Factors; Treatment Outcome

This study aims at describing the epidemiological and clinical characteristics, severity, reversibility testing and response to treatment using simple spirometry in asthmatic patients attending a model specialized Asthma Care Center.. Eligible subjects must have a suggestive clinical picture and confirmed by spirometry to have a 12% plus 200ml absolute increase in FEV1 either by reversibility testing or after a therapeutic trial with inhaled and/or oral steroid therapy. Budesonide-Formoterol Turbohaler was used for reversibility testing and for maintenance therapy with or without the addition of oral prednisolone.. One hundred and nineteen patients were eligible for the study. Age ranged between 10 -70 years. One hundred and thirteen patients (95.0%) had an FEV1 less than 80% of predicted. One hundred and five patients (88.2%) had reversibility testing of whom 72 (68.6%) had a significant reversibility. Sixty two patients (52.1%) were prescribed Budesonide-Formoterol Turbohaler only whilst 57 were prescribed both Budesonide-Formoterol Turbohaler and oral prednisolone. Patients were reviewed after a mean of 14.9 days (range 6.0-28.0). Seventy two patients (60.5%) had increased their FEV1 to more than 80% of their predicted value. By logistic regression analysis, predicted FEV1 at baseline was a significant negative predictor of a complete response.. Most patients had abnormal spirometry with more than half having an FEV1 that is 60% or less of their predicted normal reading. Reversibility testing using Budesonide-Formoterol Turbohaler confirmed the fast onset of action of its Formoterol component and helped in cutting the cost of this test. The majority improved with treatment with 60% normalizing their spirometry highlighting the feasibility and applicability of specialized asthma care centers in resource-poor countries.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Child; Developing Countries; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prednisolone; Retrospective Studies; Spirometry; Treatment Outcome; Young Adult

The use of a combination inhaler containing budesonide and formoterol (BUD/FOR) to both maintenance and quick relief therapy has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist therapy. The aim of this study was to investigate the acute effects of BUD/FOR and testing the availability of BUD/FOR for early reversibility test in patients with airway obstruction.. The study was conducted on patients who were admitted to the Department of Pulmonary Medicine, Samsun Medical Park Hospital, Samsun, Turkey.. A total of 44 patients were included in the study. The mean age of patients was 48.5 ± 17.3 (range 10-75) years and the male-to-female ratio was 36:8. The pre-bronchodilator pulmonary function test results are as follows: the mean forced vital capacity, 3,025 ± 1,162 mL (76.3% ± 23.2%); mean forced expiratory volume in 1 second (FEV1), 1,898 ± 725 mL (59.2% ± 19.1%); mean FEV1/forced vital capacity, 62.8 ± 6.3% (range 42%-70%); mean peak expiratory flow, 3,859 ± 1,779 mL (48.0% ± 19.7%); and forced expiratory flow 25%-75%, 1,295 ± 486 mL (35.8% ± 12.3%). The reversibility was positive in 26 (59.1%) patients. The absolute change and percentage of change in FEV1 were 318 ± 228 mL and 17.7% ± 11.9%, respectively. The patients were divided into two groups according to reversibility (reversible and irreversible) and both groups were compared with changes according to spirometric results. FEV1 values were statistically different between the two groups.. The fixed combination of BUD/FOR has rapid bronchodilator effect, and they can be used for early reversibility test.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Child; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Spirometry; Time Factors; Treatment Outcome; Turkey; Vital Capacity; Young Adult

In practice it is logical that inhalers are prescribed only after patients have received training and demonstrated their ability to use the device. However, many patients are unable to use their pressurised metered-dose inhaler devices (pMDIs) correctly. We assessed the relationship between asthma control and patients' ability to use their prescribed pMDIs.. Evaluation of 3,981 (46% male) primary care asthma patient reviews, which included inhaler technique and asthma control, by specialist nurses in primary care in 2009. The paper focuses on people currently prescribed pMDI devices.. Accurate data on reliever and preventer inhaler prescriptions were available for 3,686 and 2,887 patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and 525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and with a spacer, respectively. Asthma was controlled in 50% of patients reviewed. The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001) and more short burst systemic steroid prescriptions in the last year (p=0.038). Of patients using beclometasone (the most frequently prescribed preventer drug in our sample), significantly more of those using a breath-actuated pMDI device (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs alone.. Patients who are able to use pMDIs correctly have better asthma control as defined by the GINA strategy document. Beclometasone via a spacer or breath-actuated device resulted in better asthma control than via a pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique and have their ability to use these devices tested; those unable to use the device should be prescribed a spacer or an alternative device such as one that is breath-actuated.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Patient Education as Topic; Pregnadienediols; Retrospective Studies; Self Administration; Treatment Outcome; Young Adult

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Humans; Male; Primary Health Care

Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary.. Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients.. 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs.. Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our conclusions.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cost Control; Costs and Cost Analysis; Dose-Response Relationship, Drug; Drug Combinations; Drug Substitution; Ethanolamines; Fees, Pharmaceutical; Female; Fluticasone-Salmeterol Drug Combination; Humans; Hungary; Linear Models; Male; Middle Aged; Patient Compliance; Reference Standards; Retrospective Studies; World Health Organization; Young Adult

Dysphonia is one of the most common side effects of patients who use corticosteroid inhalers. The aim of this study was to investigate, prospectively, the occurrence of dysphonia in patients who used corticosteroid inhalers.. Outpatients aged 18 years or older initially treated with inhaled corticosteroids were recruited. All patients were prescribed budesonide/formoterol. Questionnaires, perceptual studies, and acoustic analysis were performed five times during the study: at study entry and after 1, 4, 8, and 12 weeks. Videostroboscopy was performed at study entry and at 12 weeks. The data collected were analyzed by repeated-measures analysis of variance tests and Wilcoxon's signed rank test (P<0.01).. Sixty-two patients were enrolled and 29 patients (M:F=19:10) completed the study. Seven patients reported that they had problems with their voice; however, there were no statistically significant changes in the perceptual studies or the acoustic analysis. The videostroboscopy showed that "injection" and "increase of mucus" significantly increased by week 12. Vocal fold bowing was not noted in any of the patients.. The results of this study showed no significant voice changes in patients using corticosteroid inhalers over a period of 3 months. However, minor mucosal changes were found on videostroboscopy.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Dysphonia; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Mucous Membrane; Nebulizers and Vaporizers; Prospective Studies; Stroboscopy; Surveys and Questionnaires; Time Factors; Vocal Cords; Voice; Young Adult

The rapid action of the long acting beta agonist formoterol allows it to be used as both a preventer and reliever in the management of asthma. The Symbicort® SMART dosing regime has been shown to reduce the number of asthma exacerbations. The aim was to determine the current prescribing of Symbicort®, the prescribing of the SMART regimen and the co-prescribing of a short acting beta agonist with this regimen by means of an audit of prescriptions dispensed in a pharmacy multiple in the U.K. Anonymised data were collected on a standard form. Symbicort® prescribing data for six months were extracted from the pharmacy Patient Medication Record (PMR). Data were stratified by age and analysed to determine adherence with Symbicort® SMART prescribing as defined by the U.K. product license. Data were received from 51 of the 118 (43.2%) pharmacies contacted. Complete information from 2484 PMRs was included in the study. 2.81% (70/2484) of patients were prescribed SMART as defined by the U.K. summary of product characteristics. Of the 18-35 year age group 7.44% (27/363) were prescribed SMART correctly. However, Symbicort® was prescribed twice a day and when required, with either the co-prescription of a SABA, or at an unlicensed dose in 2.46% (61/2484) and 0.28% (7/2484) patients respectively. The incidence of Symbicort® SMART prescribing in this study is low but may be underestimated due to unclear dosing instructions.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Medical Audit; Middle Aged; Pharmacies; United Kingdom; Young Adult

Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood.. This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler(*)) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations.. The percentage of patients with Global Initiative for Asthma-defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting beta(2)-agonist (LABA), and higher dose ICS/LABA plus short-acting beta(2)-agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies.. The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (>or=80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy.. Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Child, Preschool; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Markov Chains; Middle Aged; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Surveys and Questionnaires; Young Adult

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Drug Recalls; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; United States; United States Food and Drug Administration

When an adequate standard of asthma control is not achieved with maintenance treatment of inhaled corticosteroids, the addition of a long-acting beta(2)-adrenergic receptor agonist (LABA) bronchodilator is recommended. Using a combination product, salmeterol/fluticasone propionate (Seretide or Advair) or budesonide/formoterol (Symbicort) is preferred for convenience and avoids any risk that LABA might be used as monotherapy. As formoterol has a rapid onset of bronchodilator effect, the budesonide/formoterol combination can be used for both the maintenance and reliever components of asthma treatment (Symbicort SMART) and this is endorsed as an effective treatment by the Global Initiative for Asthma. The efficacy of this approach has been evaluated in a series of well conducted, controlled studies. Current control of asthma symptoms is improved or achieved with reduced total dose administration with Symbicort SMART compared with any reasonable alternate option. In every study, the risk of severe exacerbations was lower with Symbicort SMART than comparator treatment. Patients who benefit to the greatest extent are those with evidence of more severe asthma and greater exacerbation risk. When initiated in suitable patients in conjunction with appropriate education, Symbicort SMART is dominant in pharmacoeconomic terms. Symbicort SMART delivers improved asthma outcomes with lower treatment and social costs than any alternative.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Controlled Clinical Trials as Topic; Drug Combinations; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Humans

The purpose of this study was to determine if empirically observed differences in patient perception of, and satisfaction with, onset of effect between an active maintenance treatment and placebo are clinically meaningful to practicing clinicians. A secondary objective was to determine the lowest threshold for a clinically meaningful difference in terms of both between-group differences and maximum acceptable placebo effect.. Twelve community-based healthcare professionals participated in a Delphi consensus panel. Panelists were provided with blinded results of two clinical trials showing statistically significant treatment effects for treatment A (budesonide/formoterol [Symbicort*]) over placebo in the proportion of patients who could perceive the medication working right away and the proportion of patients satisfied with this perception. Panelists were then asked to respond to a series of questions to identify a threshold for clinically important differences in patient-perceived onset of effect and satisfaction with speed of onset of effect. All expert panelists participated in two rounds of the Delphi process.. Panelists were unanimous in their conclusion that the statistically significant results from the two trials were clinically meaningful. According to these practitioners, the empirical results presented to them, showing that patients could feel a maintenance inhaler therapy work right away, were meaningful to clinical decision-making, and the attribute could potentially improve patient adherence with therapy. A group consensus was reached that a minimum active treatment response for these outcomes should range from 50% to 75% and be 2-3 times larger than the placebo response, with a maximum placebo effect of 26-40%.. A Delphi panel study of practitioners was used to establish a meaningful range of response and a minimal important difference for interpreting results of clinical trials in which patient perception of onset of effect and satisfaction with this perception are tested. While the views of this panel may not be generalized to the entire population of practitioners in the United States, results provide insight into how a typical practitioner is likely to view clinical trial results and how the information might be used in clinical practice.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Consensus; Drug Combinations; Ethanolamines; Expert Testimony; Humans; Patient Satisfaction; Perception; Placebos; Professional Competence; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Single-Blind Method; Surveys and Questionnaires; Time Factors; Treatment Outcome

In budesonide/formoterol (Symbicort(R) Turbuhaler(R), AstraZeneca, Lund, Sweden) maintenance and reliever therapy (SMART), patients with asthma take a daily maintenance dose of budesonide/formoterol, with the option of taking additional doses for symptom relief instead of a short-acting beta(2)-agonist (SABA). This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherlands from a societal perspective.. The study was linked to a randomized, active-controlled, open-label, multicenter, 12-month clinical trial, with a prospective collection of resource use. One hundred and two patients > or =18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids (ICS) prior to the trial were included. SMART was given as two inhalations of budesonide/formoterol (100/6 microg) once daily, plus additional doses as needed. The control group was treated according to guidelines, which prescribe medium daily doses of ICS plus an SABA if needed. A long-acting beta(2)-agonist (LABA) is added if necessary. Effectiveness was measured as the proportion of asthma-control days, Asthma Control Questionnaire (ACQ) scores, the net proportion of patients with relevant ACQ improvement, and the proportion of well-controlled patients. Costs included asthma medication, physician contacts, and absence from work.. Mean total costs for SMART were 134.81 lower (95% CI: -439.48; 44.85). Production losses were 94.10 (95% CI: -300.60; 0.29) lower for SMART (10.77 vs. 104.87). No significant differences in health outcomes were seen, with 3.81 fewer asthma-control days per patient-year for SMART (95% CI: -36.8; 30.8), a 0.049 better ACQ score (95% CI: -0.21; 0.29), a 5.8% larger net proportion of improved patients (95% CI: t15.6%; 27.3%), and a 2.1% (95% CI: -25.5; 20.8%) smaller increase in the proportion of well-controlled patients.. Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs; therefore, is likely to be an alternative for guideline-directed treatment, from a health and economic perspective.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Case-Control Studies; Cost of Illness; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Ethanolamines; Female; Health Care Costs; Humans; Male; Models, Econometric; Netherlands; Randomized Controlled Trials as Topic; Regression Analysis; Treatment Outcome

Asthma is not adequately controlled in many patients. A new approach in asthma treatment, known as Budesonide/Formoterol Maintenance and Reliever Therapy has shown improvement in asthma control compared to conventional therapy regimens. As Switzerland was the first European country to formally approve budesonide/formoterol maintenance and reliever therapy, a patient follow-up programme was commenced in January 2006 to investigate its efficacy and safety in a "real-life" environment.. A non randomized uncontrolled post-marketing survey involving 420 physicians in all language regions in Switzerland was carried out. 2035 patients with asthma were enrolled. Data on current asthma treatment, asthma control and unscheduled visits due to worsening asthma were recorded. Asthma control was assessed subjectively by both the patients and the physicians as well as by means of the validated 5-item Asthma Control Questionnaire (ACQ5). An ACQ score of 0.75 or less indicates well-controlled asthma.. Data from 2006 out of 2035 patients were analysed (mean age 44.9 +/- 19.6 years, 50.5% female). With budesonide/formoterol maintenance and reliever therapy the mean ACQ5 score improved by more than 3-fold the defined minimal important difference (MID). The percentage of patients with an ACQ score < or =0.75 increased from 4.8% at baseline to 58.0% at the end of the follow-up programme. Patient satisfaction with budesonide/formoterol for both maintenance and relief was high.. Budesonide/formoterol maintenance and reliever therapy improves asthma control in a non randomised real-life setting.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Drug Combinations; Ethanolamines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Satisfaction; Practice Guidelines as Topic; Surveys and Questionnaires; Switzerland; Time Factors

Budesonide/Formoterol (Symbicort) combination therapy as both maintenance and reliever treatment (SMART) is a novel approach in asthma management. We examined its 'real-life effectiveness' in treating Malaysian patients with moderate-to-severe asthma in whom despite on combined inhaled corticosteroids and long-acting beta2-agonist, were still inadequately controlled. In a retrospective study, 22 eligible adult patients on SMART [mean (range) age: 49 (36-65) years; FEV1: 41 (21-74)% predicted] were identified from medical records of an urban-based university hospital chest clinic, and their clinical outcomes studied at three months. Another 16 patients [50 (14-66) years; 48 (20-91)% predicted] of similar severity and treatment (i.e. Symbicort maintenance treatment plus short-acting beta2-agonist as reliever), but not on SMART, were used as comparator over the same assessment period. In addition, the patients were separately interviewed with standard questionnaire on their satisfaction and compliance to the SMART approach. In SMART group, rescue treatment requirement (p<0.001) and FEV1 [median difference = 2.5%, p=0.015; mean difference: 90 ml, p=0.013] showed significant improvement while in comparator, there was significant improvement only in the requirement for rescue treatment (p=0.023). Hospital admission rates were significantly reduced in SMART group compared to the other (p=0.039), but not in emergency treatment. Five patients asked to discontinue SMART while all others were satisfied, compliant and perceived improvement of their asthma with SMART. The maximum daily doses of inhaled budesonide and formoterol were 1400 microg and 31.5 microg respectively. Our preliminary findings suggest that SMART approach can be attempted as an effective and safe treatment option for patients with inadequately controlled moderate-to-severe asthma in Malaysian setting.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Cohort Studies; Drug Combinations; Ethanolamines; Female; Humans; Malaysia; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Young Adult

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

Angiogenesis and microvascular remodelling may play a vital role in the chronic inflammatory process within asthma. One of the most important factors involved in angiogenesis is vascular endothelial growth factor (VEGF). In this study we hypothesised that an increased expression of VEGF may be involved in airway remodelling in asthma patients. To this end, we compared the histology and expression levels of VEGF and one of its receptors (VEGFR1) in bronchial tissues of patients with asthma compared with control patients. We also investigated the effect of treatment with budesonide/formoterol (Symbicort; AstraZeneca, Lund, Sweden) in the relationship between VEGF and airway remodelling.. Bronchial tissues were obtained from patients attending the West China Hospital from April to November 2006. Thirteen patients were diagnosed with moderate asthma and 10 others were treated as control. Histological and immunohistochemical comparisons between asthmatic and control patients were made at baseline, and (for asthmatic subjects) following 6 months of treatment with budesonide/formoterol.. Compared with control patients, asthmatic patients had significantly decreased respiratory parameters, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) (% predictive). Furthermore, patients with asthma had submucosal gland hyperplasia, increased smooth muscle mass, increased subepithelial fibrosis and neovascularisation. Asthmatic patients also exhibited increased expression of VEGF and VEGFR1 within epithelial cells. The increased expression of VEGF and its receptor correlated well with airway remodelling, airflow obstruction and airway hyper-responsiveness. After treatment with budesonide/formoterol for 6 months, the expression of VEGF and VEGFR1 was decreased, with correlatory decreased airway remodelling in patients with asthma.. The increased expression of VEGF and VEGFR(1) in asthmatic patients is accompanied by an increased number and size of blood vessels in asthmatic airways, as well as airway remodelling. Budesonide/formoterol therapy for 6 months can decrease the expression of VEGF and VEGFR(1) alongside airway remodelling in asthma. The inhibition of VEGF and its receptor may be a good therapeutic strategy for asthma.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Bronchi; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic; Respiratory Function Tests; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Topics: Adrenal Cortex Hormones; Asthma; Bronchoscopy; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Controlled Clinical Trials as Topic; Drug Combinations; Ethanolamines; Humans; Patient Compliance; Patient Education as Topic; Quality of Life; Respiratory Therapy