(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Asthma

The advent of inhaled corticosteroids (ICS) brought a revolution in the management of asthma, representing now the cornerstone in this pathological condition treatment. Indeed, these drugs have clearly shown to possess a high degree of both efficacy and safety. Beclomethasone dipropionate (BDP) is the first molecule tested in the early 1970s. When administered via nebulizers or pressurized metered-dose inhalers (pMDI), BDP was found to be effective in reducing the symptoms frequency and severity in asthmatic patients, even in those previously treated with low-dose oral corticosteroids. The drug was thus produced to be administered by nebulization or via pMDI. Nebulizers are a practical and efficient tool for administering inhaled drugs in patients of all degree of severity and belonging to all ages, but are especially useful for those unable to utilize other inhaler devices correctly. BDP aerosolization, when generated by modern pneumatic nebulizers, can deliver particles with a mass median aerodynamic diameter (MMAD) value of 2.9-3.7 µm. This ability allows the deposition of the drug in small caliber airways, and considerably reduces the amount of drug deposited in the oropharynx, thus improving this molecule pharmacokinetics. This review aims to analyze the factors influencing the efficacy and safety of ICS, evaluating in detail the characteristics of BDP administered by nebulization.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Humans

Airway inflammation in asthma involves not only the central airways but extends to peripheral airways. Lung deposition may be key for an appropriate treatment of asthma. We compared the clinical effects of extrafine hydrofluoroalkane (HFA)-beclomethasone-formoterol (BDP-F) versus equipotent doses of nonextrafine combination of an inhaled corticosteroid and a long acting β2-agonist (ICS-LABA) in asthma.. We identified eligible studies by a comprehensive literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Data analysis was performed with the Review Manager 5.3.5 software (Cochrane IMS, 2014).. A total of 2326 patients with asthma from ten published randomized controlled trials (RCTs) were enrolled for analysis. Change from baseline in morning pre-dose peak expiratory flow (PEF), evening pre-dose PEF and forced expiratory volume in one second (FEV1) were detected no significant differences between extrafine HFA-BDP-F and nonextrafine ICS-LABAs (p = 0.23, p = 0.99 and p = 0.23, respectively). Extrafine HFA-BDP-F did not show any greater benefit in forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%), the parameter concerning peripheral airways (MD 0.03L/s, p = 0.65; n = 877). There were no substantial differences between interventions in fractional exhaled nitric oxide (FeNO) levels or in its alveolar fraction. The overall analysis showed no significant benefit of extrafine HFA-BDP-F over nonextrafine ICS-LABA in improving Asthma Control Test (ACT) score (p = 0.30) or decreasing the number of puffs of rescue medication use (p = 0.16). Extrafine HFA-BDP-F did not lead to less exacerbations than nonextrafine ICS-LABA (RR 0.61, 95% CI: 0.31 to 1.20; I2 = 0; p = 0.15).. Enrolled RCTs of extrafine HFA-BDP-F have demonstrated no significant advantages over the equivalent combination of nonextrafine ICS-LABA in improving pulmonary function concerning central airways or peripheral airways, improving asthma symptom control or reducing exacerbation rate.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Asthma; Beclomethasone; Female; Formoterol Fumarate; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Outcome Assessment, Health Care; Publication Bias; Risk; Young Adult

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

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

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

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

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

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

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

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Respiratory Function Tests; Treatment Outcome

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

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

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Glucocorticoids; Humans; Nebulizers and Vaporizers

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchioles; Bronchodilator Agents; Disease Management; Drug Combinations; Dry Powder Inhalers; Equipment Design; Fluocinolone Acetonide; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Metered Dose Inhalers; Nebulizers and Vaporizers; Particle Size; Pregnenediones; Pressure; Pulmonary Disease, Chronic Obstructive

Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Dry Powder Inhalers; Formoterol Fumarate; Humans; Metered Dose Inhalers; Treatment Outcome

People with asthma may experience exacerbations or "attacks" during which their symptoms worsen and additional treatment is required. Written action plans may advocate doubling the dose of inhaled steroids in the early stages of an asthma exacerbation to reduce the severity of the attack and to prevent the need for oral steroids or hospital admission.. To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids (ICS) as part of a patient-initiated action plan for home management of exacerbations in children and adults with persistent asthma.. We searched the Cochrane Airways Group Specialised Register, which is derived from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to March 2016. We handsearched respiratory journals and meeting abstracts.. We included randomised controlled trials (RCTs) that compared increased versus stable doses of ICS for home management of asthma exacerbations. We included studies of children or adults with persistent asthma who were receiving daily maintenance ICS.. Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information.. This review update added three new studies including 419 participants to the review. In total, we identified eight RCTs, most of which were at low risk of bias, involving 1669 participants with mild to moderate asthma. We included three paediatric (n = 422) and five adult (n = 1247) studies; six were parallel-group trials and two had a cross-over design. All but one study followed participants for six months to one year. Allowed maintenance doses of ICS varied in adult and paediatric studies, as did use of concomitant medications and doses of ICS initiated during exacerbations. Investigators gave participants a study inhaler containing additional ICS or placebo to be started as part of an action plan for treatment of exacerbations.The odds of treatment failure, defined as the need for oral corticosteroids, were not significantly reduced among those randomised to increased ICS compared with those taking their usual stable maintenance dose (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.68 to 1.18; participants = 1520; studies = 7). When we analysed only people who actually took their study inhaler for an exacerbation, we found much variation between study results but the evidence did not show a significant benefit of increasing ICS dose (OR 0.84, 95% CI 0.54 to 1.30; participants = 766; studies = 7). The odds of having an unscheduled physician visit (OR 0.96, 95% CI 0.66 to 1.41; participants = 931; studies = 3) or acute visit (Peto OR 0.98, 95% CI 0.24 to 3.98; participants = 450; studies = 3) were not significantly reduced by an increased versus stable dose of ICS, and evidence was insufficient to permit assessment of impact on the duration of exacerbation; our ability to draw conclusions from these outcomes was limited by the number of studies reporting these events and by the number of events included in the analyses. The odds of serious events (OR 1.69, 95% CI 0.77 to 3.71; participants = 394; studies = 2) and non-serious events, such as oral irritation, headaches and changes in appetite (OR 2.15, 95% CI 0.68 to 6.73; participants = 142; studies = 2), were neither increased nor decreased significantly by increased versus stable doses of ICS during an exacerbation. Too few studies are available to allow firm conclusions on the basis of subgroup analyses conducted to investigate the impact of age, time to treatment initiation, doses used, smoking history and the fold increase of ICS on the magnitude of effect; yet, effect size appears similar in c. Current evidence does not support increasing the dose of ICS as part of a self initiated action plan to treat exacerbations in adults and children with mild to moderate asthma. Increased ICS dose is not associated with a statistically significant reduction in the odds of requiring rescue oral corticosteroids for the exacerbation, or of having adverse events, compared with a stable ICS dose. Wide confidence intervals for several outcomes mean we cannot rule out possible benefits of this approach.

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Humans; Randomized Controlled Trials as Topic

The high-strength formulation of extrafine beclometasone dipropionate/formoterol fumarate (BDP/Form) 200/6 µg has been developed to step up inhaled corticosteroid treatment, without increasing the dose of the bronchodilator, in patients who are not controlled with previous therapies. Two clinical studies have evaluated efficacy of high-strength BDP/Form as compared with another high-dose fixed combination and BDP monotherapy. Overall, data show that BDP/Form 200/6 μg improves lung function and has beneficial effects on symptoms, use of rescue medication and asthma control, with an acceptable safety profile comparable with that of high-dose fluticasone propionate/salmeterol. Therefore, BDP/Form 200/6 μg could be considered as an effective and safe treatment for patients with asthma who are not adequately controlled with high doses of inhaled corticosteroid monotherapy or medium doses of inhaled corticosteroid/long-acting β2-agonist combinations.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Combinations; Formoterol Fumarate; Humans

Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β2-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.. This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.. pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.

Topics: Albuterol; Androstadienes; Asthma; Beclomethasone; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Lung; Metered Dose Inhalers; Mometasone Furoate; Pregnadienediols

Long-acting muscarinic antagonists (LAMA), a class of drugs with proven effectiveness in chronic obstructive pulmonary disease (COPD), are being considered as an add-on option for adults with asthma whose condition is uncontrolled on inhaled corticosteroids (ICS). It is important to assess the safety and efficacy of LAMA add-on as an alternative to the prolonged use of higher doses of ICS, which are known to cause undesirable side effects in some people.. To compare the effects of adding a LAMA to any dose of ICS versus increasing the dose of ICS, for uncontrolled asthma in adults.. We searched the Cochrane Airways Group Specialised Register (CAGR) from its inception in 1995 to April 2015, imposing no restriction on language of publication. We also handsearched trial registries, reference lists of primary studies and existing reviews, as well as manufacturers' websites.. We looked for parallel or cross-over randomised controlled trials lasting at least 12 weeks, in which adults whose asthma was not well controlled on ICS alone were randomised to treatment with LAMA add-on to ICS or with an increased dose of ICS. Trials were excluded if patients were taking long-acting beta2-agonists during the study period.. Two review authors independently screened the searches and extracted data from studies meeting all the inclusion criteria. We used Covidence to manage duplicate screening, data extraction and risk of bias judgements, and to form a consensus where discrepancies arose. We used standard methods expected by The Cochrane Collaboration.The pre-specified primary outcomes were exacerbations requiring a course of oral corticosteroids (OCS), effects on quality of life and serious adverse events.. One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment periods.Compared with people taking a double dose of ICS, fewer people taking a LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence intervals for both outcomes did not exclude the possibility that double dose ICS was more effective. Serious adverse events and exacerbations requiring hospitalisation occurred in similarly low numbers of people taking each treatment, but confidence intervals were too wide to suggest that the two treatment options were equivalent.Asthma-related quality of life was similar in both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI - 0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale measuring asthma control than those increasing their ICS dose (MD in change from baseline - 0.18, 95% CI - 0.34 to - 0.02), although the difference was clinically small. Evidence was deemed low quality for both quality of life and asthma control.There was moderate-quality evidence that participants' trough forced expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to 0.17).. Only one randomised trial was found, comparing tiotropium add-on to increased dose beclomethasone. Differences between the treatments were too small or imprecise to understand whether adding a LAMA to ICS is safer or more effective than increasing the dose of ICS, and there is a possibility of carry-over effects due to the study's cross-over design. LAMA add-on may lead to more improvement in lung function (FEV1) than an increased dose of ICS.The results of this review, alongside pending results from related reviews assessing the use of LAMA against other treatments, will help to define the role of these drugs in asthma management, and this review should be updated as results from future trials emerge. Studies assessing the role of LAMA add-on should be longer and include a double-ICS treatment arm so that the results can be interpreted in the context of the guideline-recommended treatment options that are available to physicians.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Tiotropium Bromide

Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma.. To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration.. We searched the Cochrane Airways Group Asthma Trials Register until January 2015.. We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals.. Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible.. We included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events.A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials e. In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease.. The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs.. The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler DPI is easy to use.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Drug Delivery Systems; Dry Powder Inhalers; Ethanolamines; Formoterol Fumarate; Humans; Lung; Particle Size

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

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

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

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

Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies.. To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014).. Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only.. At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy.. We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.The eight included trials were assessed under seven separate comparisons. Pharmacological interventionsPrimary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions.. inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects. Non-pharmacological interventionsPrimary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions.. the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting β-agonists, and less frequent use of short-acting β-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed.. Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.

Topics: Adrenal Cortex Hormones; Algorithms; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Magnesium Sulfate; Muscle Relaxation; Nitric Oxide; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Theophylline

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Chemistry, Pharmaceutical; Ethanolamines; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Metered Dose Inhalers; Particle Size; Pressure; Pulmonary Disease, Chronic Obstructive

Inhaled corticosteroids (ICSs) are the mainstay of anti-inflammatory treatment in subjects with asthma and COPD. This review evaluates the role of nebulizers as an alternative to inhalers for delivering ICSs in asthma and COPD. I selected 16 randomized, placebo-controlled, blinded, long-term studies, mostly carried out in asthma (n = 14) and COPD. Nebulized budesonide has been demonstrated to be effective and safe in children ages 1-8 years, and, with less evidence, in infants and adults with asthma. Other investigations, with the addition of in vitro and in vivo comparison studies, have shown that nebulized beclomethasone, fluticasone, and flunisolide are effective alternatives to nebulized budesonide in asthma and COPD. Efficient delivery of nebulized ICSs requires that the nebulizer system, the nebulized drug formulation, and the inhaling subject interact properly. The practices of mixing nebulized ICSs with bronchodilators and using nebulized ICSs in acute settings are promising, but require further confirmations, and at present cannot be recommended. I conclude that nebulizers may be considered as an effective alternative to inhalers for delivering ICSs and can be recommended to asthmatic and COPD subjects who are unwilling or unable to use inhalers. Newer formulations could possibly offer a relevant advance for a more efficient nebulization of ICSs.

Topics: Administration, Inhalation; Androstadienes; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Equipment Design; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

Classifying disease activity in asthma relies on clinical and physiological variables, but these variables do not capture all aspects of asthma that distinguish levels of disease activity. We used data from two pivotal trials of montelukast in asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and airway obstruction lability. Then we performed discriminant analysis (DA) based on disease activity classification. PCA revealed 6 factors (daytime asthma control, nighttime-predominant asthma control, airway obstruction, exacerbations, clinical lability, airway obstruction lability) that explained 76% of the variance between outcome variables. Although airway obstruction lability (comprising both diurnal variability in peak expiratory flow and diurnal variability in β-agonist use) accounted for only 6% of the explained variance in PCA, in DA it was more accurate (canonical coefficient 0.75) than traditional measures of asthma severity such as obstruction (-0.54) and daytime control (-0.56) in distinguishing between high and low disease activity. We conclude that airway obstruction lability, a parameter not typically captured in clinical trials, may contribute to more complete assessment of asthma disease activity and may define an emerging clinical target of future therapy.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Circadian Rhythm; Clinical Trials, Phase III as Topic; Cyclopropanes; Drug Administration Schedule; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfides; Treatment Outcome; Young Adult

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

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

Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents for the management of chronic persistent asthma and are therefore recommended as first-line antiasthmatic therapy in children and adults. In various settings, the administration of ICS via nebulizer rather than hand-held inhaler (HHI) may have certain advantages, as many patients with HHI fail to use these devices properly or efficiently. In particular, young children, the elderly, the acutely ill, and those with restricted dexterity may be unable to coordinate inhalation with actuation of the device or to generate sufficient inspiratory flow to operate breath-actuated devices effectively. Compliance with nebulized therapy may also be better than that with a pressurized metered-dose inhaler (pMDI) plus spacer. Systematic reviews conclude that there is no significant difference in clinical effects between nebulizers and HHI. Performance and clinical effect of nebulization are influenced by several technical aspects such as the nebulizer-drug combination, nebulizer type, output and lung deposition. Among the currently available ICS, nebulized beclometasone dipropionate (BDP) has been in clinical use for more than 35 years, and has demonstrated marked clinical efficacy and a favorable tolerability profile in children and adults with chronic persistent asthma. The clinical efficacy of nebulized beclometasone is discussed in the present review using data from 13 published studies, which included a total of 1250 patients. Three multicenter, randomized, double-blind studies showed that nebulized BDP is as effective as BDP via pMDI plus spacer in a 2:1 dose ratio. Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. In all these trials, treatment-related adverse effects were generally uncommon, most were mild-to-moderate in severity, and most were associated with the respiratory system. Meta-analyses show that BDP, like other inhaled corticosteroids, has no major influence on patient height, urinary cortisol concentration, or bone metabolism, thus suggesting the absence of growth retardation or any marked effect on adrenal function or the hypothalamic-pituitary-adrenal axis when used in the approved dose range. Overall, nebulized BDP appears to have a particularly important place in asthma therapy: as a general alternative to HHIs (e.g. in patients with poor H

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Age Factors; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Patient Education as Topic; Patient Satisfaction; Practice Guidelines as Topic

Long-acting inhaled ss(2)-adrenergic agonists (LABAs) are recommended as 'add-on' medication to inhaled corticosteroids (ICS) in the maintenance therapy of asthmatic adults and children aged two years and above.. To quantify in asthmatic patients the safety and efficacy of the addition of LABAs to ICS in patients insufficiently controlled on ICS alone.. We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until May 2008.. We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults.. Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events.. Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 microg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and 38%. Studies recruiting adults dominated the analysis (6203 adult participants versus 605 children). The subgroup estimate for paediatric studies was not statistically significant (RR 0.89, 95% CI 0.58 to 1.39) and includes the possibility of the superiority of ICS alone in children.Higher than usual dose of LABA was associated with significantly less benefit. The difference in the relative risk of serious adverse events with LABA was not statistically significant from that of ICS alone (RR 1.06, 95% CI 0.87 to 1.30). The addition of LABA led to a significantly greater improvement in FEV(1) (0.11 litres, 95% 0.09 to 0.13) and in the proportion of symptom-free days (11.88%, 95% CI 8.25 to 15.50) compared to ICS monotherapy. It was also associated with a reduction in the use of rescue short-acting ss(2)-agonists (-0.58 puffs/day, 95% CI -0.80 to -0.35), fewer withdrawals due to poor asthma control (RR 0.50, 95% CI 0.41 to 0.61), and fewer withdrawals due to any reason (RR 0.80, 95% CI 0.75 to 0.87). There was no statistically significant group difference in the risk of overall adverse effects (RR 1.00, 95% 0.97 to 1.04), withdrawals due to adverse health events (RR 1.04, 95% CI 0.86 to 1.26) or any of the specific adverse health events.. In adults who are symptomatic on low to high doses of ICS monotherapy, the addition of a LABA at licensed doses reduces the rate of exacerbations requiring oral steroids, improves lung function and symptoms and modestly decreases use of rescue short-acting ss(2)-agonists. In children, the effects of this treatment option are much more uncertain. The absence of group difference in serious adverse health events and withdrawal rates in both groups provides some indirect evidence of the safety of LABAs at usual doses as add-on therapy to ICS in adults, although the width of the confidence interval precludes total reassurance.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

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

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

Written action plans providing guidance in the early treatment of asthma exacerbations have traditionally advocated doubling of inhaled corticosteroids (ICS) as one of the first steps in treatment.. To compare the clinical effectiveness of increasing the dose of ICS versus keeping the usual maintenance dose as part of a patient-initiated action plan at the onset of asthma exacerbations.. We searched the Cochrane Airways Group Specialised Register (last search October 2009) which is derived from searches of CENTRAL, MEDLINE, EMBASE and CINAHL, as well as handsearched respiratory journals and meeting abstracts.. Randomised controlled trials (RCTs) that compared the strategy of increasing the daily dose of ICS to continuing the same ICS dose in the home management of asthma exacerbations in children or adults with persistent asthma on daily maintenance ICS.. Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information.. Five RCTs (four parallel-group and one cross-over) involving a total of 1250 patients (28 children and 1222 adults) with mild to moderate asthma were included. The mean daily baseline ICS dose was 555 mcg (range 200 mcg to 795 mcg) and the mean daily ICS dose achieved following increase was 1520 mcg (range 1000 mcg to 2075 mcg), in CFC beclomethasone dipropionate equivalents. Three parallel-group studies in adults (two doubling and one quadrupling; mean achieved daily dose of 1695 mcg with a range of 1420 to 2075 mcg), involving 1080 patients contributed data to the primary outcome. There was no significant reduction in the need for rescue oral corticosteroids when patients were randomised to the increased ICS compared to stable maintenance dose groups (OR 0.85, 95% CI 0.58 to 1.26). There was no significant difference in the overall risk of non-serious adverse events associated with the increased ICS dose strategy, but the wide confidence interval prevents a firm conclusion. No serious adverse events were reported.. There is very little evidence from trials in children. In adults with asthma on daily maintenance ICS, a self-initiated ICS increase to 1000 to 2000 mcg/day at the onset of an exacerbation is not associated with a statistically significant reduction in the risk of exacerbations requiring rescue oral corticosteroids. More research is needed to assess the effectiveness of increased ICS doses at the onset of asthma exacerbations (particularly in children).

Topics: Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Disease Progression; Humans; Randomized Controlled Trials as Topic

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

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

Long-acting ss(2)- agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children.. To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma.. We searched the Cochrane Airways Group Asthma Trials Register (May 2008).. We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals.. Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible.. A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS:(1) The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV(1) at baseline was 80% of predicted or above in 10 studies; FEV(1) 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1 with the addition of LABA (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant group differences in symptom-free days, hospital admission, quality of life, use of reliever medication, and adverse events. Withdrawals occurred significantly less frequently with the addition of LABA.(2) A total of seven studies assessed the addition of LABA to ICS therapy compared with an increased dose of ICS randomising 1021 children. The mean age of participants was 8 years with 67% of males. The baseline mean FEV(1) was 80% of predicted or above in 2 of the 3 studies reporting this characteristic. All trials enrolled participants who were inadequately controlled on a baseline dose equivalent to 400 mcg/day of beclomethasone or less. There was no group significant difference in the risk of an exacerbation requiring oral steroids with the combination of LABA and ICS compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The increased risk of hospital admission with combination therapy was also not statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose ICS, use of LABA was associated with a significantly greater improvement in morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were insufficient data to aggregate data on FEV(1), symptoms, rescue reliever use, and quality of life. There was no s. In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but was superior for improving lung function compared to the same dose of ICS. Similarly, compared to a double dose ICS, the combination of LABA and ICS did not significantly increase the risk of exacerbations requiring oral steroids, but was associated with a significantly greater improvement in PEF and growth. The possibility of an increased risk of rescue oral steroids and hospital admission with LABA therapy needs to be further examined.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Salmeterol Xinafoate

The risk of cataracts associated with the long-term use of inhaled corticosteroids (ICS) is poorly recognized, yet may be of major public health importance. The aim of this study was to determine the dose-response relationship of ICS use and risk of cataracts in adults.. A systematic review and meta-analysis was performed of case-control studies of cataracts and ICS use, which included at least two doses of ICS and in which the number of cases and controls using each dose of ICS was reported. The primary outcome variable was risk of cataracts.. Four case-control studies were identified, with a total of 46 638 cases and 146 378 controls. There was a significant relationship between the risk of cataracts and ICS dose, with a random effects pooled odds ratio for risk of cataracts per 1000 microg increase in daily beclomethasone dipropionate dose of 1.25 (95% CI: 1.14-1.37).. The risk of cataracts was increased by approximately 25% for each 1000 microg per day increase in the dose of beclomethasone dipropionate or equivalent. These findings reinforce the importance of prescribing within the therapeutic dose-response range for ICS in asthma and the need to determine the dose-response relationship for the efficacy of ICS in COPD. Screening for the presence of cataracts could usefully be undertaken in older subjects with asthma and COPD, particularly current or ex-smokers.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Beclomethasone; Cataract; Dose-Response Relationship, Drug; Humans; Pulmonary Disease, Chronic Obstructive; Risk Factors

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

A question with respect to asthma therapy revolves around the issue of whether better efficacy occurs with an ultrafine-particle inhaled corticosteroid because of better lung deposition into the distal airways. This article reviews particle size and delivery devices of different steroids, clinical outcomes of small- versus large-particle steroids, and the issue of pharmacoeconomics.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Particle Size; Treatment Outcome

The combination of inhaled corticosteroids (ICS) and long acting Beta-2 agonists (LABA) represents the mainstay of current treatment of moderate to severe persistent asthma. Corticosteroids and LABA combine the main pillars of asthma therapy--inhibition of inflammation and bronchodilation--and they may potentiate each other when they simultaneously reach the pharmacological target. A new extra-fine formulation containing the combination of inhaled beclometasone (BDP) and formoterol (F) (with the non polluting HFA-Hydrofluoroalkane-134a as propellant) is now available on the market. The extra-fine formulation increases the deposition into the peripheral airways and a greater proportion of the inhaled compound reaches the pharmacological target. Thus, the dose of ICS can be decreased and the risk-benefit profile improves. The efficacy and tolerance of BDP/F extra-fine combination has been documented in randomized clinical trials into which patients with moderate to severe asthma were included. These trials confirmed that the new extra-fine combination is as effective as the other fixed combinations.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Forecasting; Formoterol Fumarate; Humans

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

To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non-vertebral fracture in adults.. A systematic review and meta-analysis of case-control studies of non-vertebral fractures in adults, in which at least two doses of ICS were reported as the dose of beclomethasone dipropionate (BDP) or equivalent.. Five case-control studies were identified, with a total of 43 783 cases and 259 936 controls. There was an association between the risk of non-vertebral fracture and increasing dose of BDP. The random-effects odds ratio of relative risk for a non-vertebral fracture was 1.12 (95% confidence interval 1.00-1.26) per 1000 microg increase in the daily dose of BDP or equivalent.. In older adults, the relative risk of non-vertebral fractures increases by about 12% for each 1000 microg/day increase in the dose of BDP or equivalent. The magnitude of this risk was considerably less than other common risk factors for fracture in the older adult.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Case-Control Studies; Dose-Response Relationship, Drug; Fractures, Bone; Humans; Risk

Combinations of a long-acting beta(2)-agonist (LABA) and an inhaled corticosteroid (ICS) are effective and safe options in asthma management.. To review available data on a recently developed combination of beclometasone dipropionate (BDP) and formoterol (F) given via a pressurized metered-dose inhaler.. Published data on preclinical and clinical studies were reviewed.. In the treatment of asthma, BDP/F was shown to be at least as effective and well-tolerated as other available combinations of ICS and LABA with the advantage of a better cost effectiveness, and more effective in improving asthma control than BDP and formoterol given via separate inhalers. The extra-fine BDP/F combination appears to be a valuable therapeutic option in the management of asthma.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans; Metered Dose Inhalers; Particle Size

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

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

The known efficacy of fluticasone propionate in adults, comparable at half-dosage of corticosteroids has been validated by the market authorization (MA) and by the national and international guidelines for beclomethasone. This could be partly explained by its pharmacological properties, affinity for glucocorticosteroid receptors, lung deposition and lipophilicity. The limited systemic adverse events is due to its low bioavailability, optimal hepatic clearance, high plasma protein binding. The efficacy in asthmatic children has been confirmed in clinical studies showing a "plateau" efficacy between 100 and 200 microg/d for the majority of children. Most children are controlled by such dosages: the added value of increasing posology on asthma control exists but is small. A high off-label posology does not allow more quickly asthma control and therefore is not justified. A twice daily dosing is more efficient, particularly for initiation of maintenance therapy, than a once daily dosing. A literature survey confirms that, at MA recommended daily doses in children (100-200 microg), fluticasone propionate has no clinically significant effect either on hypothalamic-pituitary-adrenal (HPA) axis (basal function or stimulation tests), bone or growth velocity. However, high daily doses (higher to 500 microg/day) for long periods expose to systemic adverse effects with measurable consequences on growth rate, bone density (decreasing biochemical makers of bone formation) and HPA function. Several cases of adrenal insufficiency that may have led to acute adrenal crisis have been reported in 4- to 10-year-old children receiving fluticasone propionate in doses between 500 to 2000 microg daily. In case of surgery or infection, a preventive treatment of adrenal insufficiency with hydrocortisone should be proposed for children treated for more than 6 months with such high daily doses. Such children need definitely an advice from paediatricians specialized in chest diseases as well as in endocrinology. It is important to recall that the clinical benefit of daily doses of inhaled corticosteroids higher than recommended is low and that the good use of inhaled corticosteroids particularly in children lays on the careful search of the minimal efficient daily doses.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Infant; Practice Guidelines as Topic

Inhaled corticosteroids remain the most important therapy for chronic asthma in both adults and children. As all inhaled corticosteroids act by binding to a common glucocorticoid receptor there is little evidence of any real difference in clinical efficacy between the different inhaled corticosteroids. The main potential differences are in their propensity to cause side effects. Local side effects such as a hoarse voice do occur in a proportion of adults and there is some limited evidence that ciclesonide may cause less local side effects. In adults there is little evidence for clinically important systemic side effects from doses of inhaled steroids below 800 mcg/day (beclomethasone equivalent). Above this dose a proportion of patients may show some adrenocortical suppression, though it is unlikely to be of clinical importance. Data on bone mineral density and fracture rates is discrepant, but an overview would suggest that below 800 mcg/day there is no increase in fracture risk whereas above this dose there might be an increased fracture risk. The properties of ciclesonide would suggest that it has less propensity for systemic side effects, but large long term studies are needed to confirm this. In children using inhaled steroids at above-licensed doses reductions in short-term growth can occur, but there is little evidence for reductions in long-term growth at normal doses. At above-licensed doses, biochemical adrenocortical suppression can occur with some unusual but documented cases of clinical Addisonian crisis. Limited evidence in paediatric age groups would suggest that ciclesonide may have some advantage although it is not as yet licensed in all countries for paediatric use. Data on differences in side effects between normal and asthmatic patients, and between asthmatic patients with near-normal lung function compared to those with impaired lung function, indicate that inhaled corticosteroids (particularly fluticasone) are absorbed more in those with normal lung function; this strongly supports stepping down the inhaled steroid dose when asthma is controlled - as is recommended in asthma guidelines.

Topics: Administration, Inhalation; Adrenal Glands; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone and Bones; Dose-Response Relationship, Drug; Glucocorticoids; Growth; Hoarseness; Humans; Nebulizers and Vaporizers; Practice Guidelines as Topic; Pregnenediones

The evidence for hypothalamic-pituitary-adrenal axis (HPA) suppression by inhaled corticosteroids (ICS) was found to be conflicting. Reviewers have not distinguished between gold standard and basal adrenal function tests. The utility of the latter is limited by physiological and pathological variability as well as by methodological concerns. The risk of HPA suppression in asthmatic children and adolescents treated with ICS, as determined by gold standard adrenal function tests, needs to be established. A systematic review of the literature from January 1973 to July 2005 was performed. The Medline and Cochrane databases were searched, the reference lists of retrieved articles were inspected and pharmaceutical companies were approached. Randomized-controlled trials, cohort and case-control studies designed to detect HPA suppression caused by ICS, diagnosed by the insulin tolerance test (ITT) or the metyrapone test, performed on asthmatics of all ages not on oral steroids, were included and assessed for methodological quality. Of the 22 identified studies only four met the criteria for inclusion. All of these were published before 1988 and only one was methodologically sound. The cohort study showed that the baseline risk for HPA suppression is 0% while the absolute risk is 100% in asthmatic children treated with a beclomethasone dipropionate metered dose inhaler at a dose of 250-600 mug/m(2)/day for 6-42 months. As suggested by other observations these results could be generalized to other ICS. They may be of clinical significance especially if children are subjected to stress. Further research is needed to establish the cumulative dose for all ICS at which HPA suppression will be precipitated. Guidelines for future trials are suggested.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenal Insufficiency; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Reproducibility of Results; Research Design; Risk Assessment; Treatment Outcome

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

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

The magnitude of improvement of respiratory symptoms (RS) and expiratory flows (EF) following corticosteroid treatment may vary from one asthmatic patient to another. The distribution of ratio of improvement of the above parameters was assessed in 937 patients with asthma of variable severity who took part in three clinical trials comparing the effects of chlorofluorocarbon-propelled beclomethasone dipropionate (CFC-BDP) with similar (n:316) or half-doses (n:581) of extrafine hydrofluoroalkane-propelled (HFA-BDP) on asthma control. We calculated the ratio of improvement of shortness of breath, wheezing, sleep disturbance, cough, and chest tightness over the following physiological parameters: forced expiratory volume in 1s (FEV1), FEF(25/75%), morning peak expiratory flow, and FVC, from the baseline value to the last set of measures in the study, while on the study medication. We hypothesized that the ratio of RS/EF would have a normal distribution and would be higher with extrafine HFA-BDP compared with CFC-BDP, which has a larger particle size, when FEV1 is used, as it mostly assesses large airways. Ratios of improvement were normally distributed for both drugs and no significant shift in its distribution curve was found for HFA-BDP. The ratio of changes in FEF(25/75%)/FEV1 was similar in the two groups. In conclusion, the ratio of improvement of RS/EF is normally distributed over a narrow range, showing a generally good correlation between improvements in EF and symptoms in asthma; it was, however, similar for the two BDP molecules tested. This may suggest that this ratio is not useful for evaluating the effect of corticosteroids on small airways, or that extrafine HFA-BDP acts at the level of large- to moderate-caliber airways to produce most of its beneficial effect.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Female; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiratory Function Tests

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

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

A reduced response to beta-adrenoceptor agonists has been reported in airways of asthmatic subjects. Mechanisms for beta-adrenoceptor dysfunction are (1) inactivation or downregulation of beta-adrenoceptors by specific agonists (homologous desensitization) or by inflammatory mediations (heterologous desensitization), (2) inactivation or downregulation of second messengers of beta-adrenoceptor pathway. Studies from our laboratory have shown that allergen challenge of passively sensitized human bronchi causes a beta-adrenoceptor dysfunction as a result of reduced activity of the receptor-coupled Gs protein. The dysfunction was prevented by leukotriene-receptor antagonists or a cell membrane stabilizer, but not by an antihistimine or indomethacin, suggesting a central role of leukotrienes released from resident inflammatory cells in its genesis. Furthermore, the beta-adrenoceptor response and Gs protein function after allergen exposure were restored by short-term (3 h) incubation with beclomethasone dipropionate, suggesting an effect independent of gene transcription. Restoration of the intracellular beta-adrenoceptor effector pathway may contribute to the efficacy of corticosteroids in the acute treatment of asthma.

Topics: Adrenergic beta-Agonists; Allergens; Asthma; Beclomethasone; Humans; In Vitro Techniques; Leukotriene Antagonists; Models, Biological; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Receptors, Adrenergic, beta

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

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

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of January 2006.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Eight studies (1260 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

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

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

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

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

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

As discussed above, pharmacogenetics offers the opportunity to ascertain associations between genetic variability and response (both salutary and adverse) to various asthma medications. Although there have been multiple asthma pharmacogenetic studies, the field of pharmacogenetics is still in its infancy. As this field advances, it is estimated that an increasing proportion of individual variation in responses to pharmacotherapy will be predictable based on associations with particular genetic polymorphisms or patterns of polymorphisms. These associations hold out the promise of being able to individualize pharmacotherapy by providing specific therapy to those most likely to respond, while avoiding therapy in those most likely to suffer adverse effects. Currently, only the pharmacogenetic effects of position 16 of the beta-adrenergic receptor appear to be of sufficient magnitude to affect asthma therapy, but further understanding of the mechanism of this association as well as prospective replication with long-acting beta-agonists is still required to bring pharmacogenetics into the clinical arena. Most other pharmacogenetic effects are likely to be of smaller magnitude or, as with 5-LO or CRHR1 polymorphisms, less common. Thus, ultimately, we most likely will use "panels" of polymorphisms to calculate the relative risk-benefit ratio of a particular therapeutic course for an individual patient. It is hoped that, within the next decade, pharmacogenetic information will allow us to treat those who can benefit most from particular asthma medications and to avoid toxicity by administering medications to those unlikely to experience toxicity. If pharmacogenetics fulfills its promise, then not only will we be able to administer corticosteroids and other therapies to pediatric patients with asthma who are most likely to respond or to those least likely to experience adverse effects but we also will be able to introduce or develop drugs for asthma that would otherwise have been held back due to potential toxicity in a subset of patients.

Topics: Acetates; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cyclopropanes; Genotype; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Quinolines; Receptors, Adrenergic, beta; Sulfides

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Biological Therapy; Child; Controlled Clinical Trials as Topic; Disease Models, Animal; Eosinophilia; Etanercept; Forecasting; Glucocorticoids; Haplorhini; Humans; Hypereosinophilic Syndrome; Immunoglobulin E; Immunoglobulin G; Immunosuppressive Agents; Interleukin-5; Omalizumab; Receptors, Tumor Necrosis Factor; Time Factors; Tumor Necrosis Factor-alpha

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

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

Inhaled beclomethasone dipropionate (BDP) has been, together with inhaled budesonide, the mainstay of anti-inflammatory therapy for asthma for many years. A range of new prophylactic therapies for asthma is becoming available and BDP has been reformulated using a hydrofluoroalkane-134a (HFA) propellant which is free from chlorofluorocarbon (CFC).. The objectives of this review were to: (1) Compare the efficacy of BDP with placebo with both CFC and HFA propellants in the treatment of chronic asthma. (2) Explore the possibility that a dose response relationship exists for BDP in the treatment of chronic asthma. (3) To provide the best estimate of the efficacy of BDP as a benchmark for evaluation of newer asthma therapies.. Electronic searches were current as of January 2003.. Randomised parallel group design trials for a minimum period of four weeks, in children and adults comparing CFC-BDP or HFA-BDP with placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. We analysed data with RevMan Analyses 1.0.2.. 60 studies recruiting 6542 participants met the inclusion criteria. CFC-BDP (57 studies): In non-oral steroid treated patients, at doses of 400 mcg/day or less CFC-BDP produced significant improvements from baseline in a number of efficacy measures compared with placebo, including forced expiratory volume in one second (FEV1) 360 ml (95% CI 260 to 460); FEV1 (% predicted) WMD 12.41% (95% CI 8.18 to 16.64) and morning peak expiratory flow rate (am PEF) WMD 35.95 L/min (95% CI 27.85 to 44.04). BDP also led to reductions in rescue beta-2 agonist use compared with placebo of -2.32 puffs/d (95% CI -2.55 to -2.09) and reduced the relative risk (RR) of trial withdrawal due to an asthma exacerbation 0.25 (95% CI 0.12 to 0.51). Subgroup analyses based on treatment duration provide support to the proposal that a treatment period of greater than four weeks is required to realise a fuller treatment effect. In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD -4.91 mg/d (95% CI -5.88 to -3.94 mg/d) and greater likelihood of withdrawing oral steroid treatment RR 8.02 (95% CI 3.23 to 19.92). HFA-BDP (3 studies): In non-oral steroid-treated patients, HFA-BDP was significantly more effective than placebo in improving FEV1, morning and evening PEF, FEF25 to 75%, reduced asthma symptoms and beta2-agonists daily consumption. Significant effects for such outcomes were apparent after six weeks of treatment. In oral steroid treated patients, HFA-BDP improved significantly FEV1 and am PEF. The summary estimates for these outcomes suggested a high level of heterogeneity, and divergent aims of the studies may contribute to the variation we observed. Limited data on adverse events were reported.. This review has quantified the efficacy of CFC-BDP and HFA-BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in people with severe asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic

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

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

Inhaled corticosteroids have a key role in the treatment of asthma and chronic obstructive pulmonary disease. In recent times, beclometasone dipropionate has been reformulated in pressurised metered dose inhalers (pMDIs), using hydrofluoroalkanes (HFAs) as a propellant. Extensive toxicological testing has shown that HFA-propellants are well tolerated. Among the reformulated beclometasone dipropionate-containing pMDIs, only the characteristics of the two Qvar formulations have been thoroughly explored. Compared to the reference beclometasone dipropionate formulation, the mass median aerodynamic diameter of the Qvar formulations are substantially smaller (1.1 vs 4.0 microm), whereas that of Modulite averages 2.6 microm. Scintigraphic and pharmacokinetic studies indicate a higher lung deposition for both the Qvar and the Beclazone formulations, compared with reference beclometasone dipropionate formulation. Since the 2- to 3-fold increase in pulmonary deposition results in a 2.6- to 3-fold difference in relative efficacy for Qvar, half the dose of the reference beclometasone dipropionate formulation has been currently recommended in adult patients with asthma, a recommendation that is supported by a large number of clinical trials. Conversely, the design of the studies conducted to compare the efficacy of Qvar with fluticasone propionate and budesonide does not allow establishing their equivalence on a milligram per milligram basis. Good studies on the bioequivalence between the reference beclometasone dipropionate formulation and the Modulite or Beclazone formulations are not available.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Therapeutic Equivalency

Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory disease or any known aetiology. In children with non-specific cough the possibility of asthma being the underlying disorder is often raised (so called cough variant asthma). The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma.. To determine the efficacy of inhaled corticosteroids in non-specific cough in children over the age of two years.. Searches were conducted on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Searches were current as of March 2004.. All randomised (randomised and quasi-randomised) controlled clinical trials in which an inhaled corticosteroid (beclomethasone (BDP), fluticasone (FP), triamcinalone (TAA) or any other corticosteroid) were given for cough in children over two years of age were included. Two review authors independently assessed articles for inclusion and methodological quality.. Data from trials was extracted by both review authors and entered into the Cochrane Collaboration software program RevMan Analyses 1.0.2.. Two trials met the inclusion criteria (123 participants). One compared inhaled beclomethasone dipropionate (400 micrograms per day) with placebo and the other compared fluticasone propionate (2 mg per day for 3 days followed by 1 mg per day for 11 days) with placebo. Both studies used metered dose inhalers via a spacer. With the lower dose of inhaled corticosteroid there was no significant difference between the beclomethasone and placebo groups. With the higher dose there was a significant improvement in nocturnal cough frequency after two weeks in children presenting with persistent nocturnal cough. However, a significant but smaller improvement was also seen with placebo.. In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial.

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

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

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

Most clinicians and patients would intuitively say that the inhaler device used influences the outcome achieved in asthma. However, it is important to have objective evidence to support or refute this view. Systematic reviews have suggested that there is no difference in clinical effectiveness between dry powder inhalers and metered-dose inhalers. However, the studies included in the review were randomised clinical trials and not studies based on real-life clinical practice. In the real world, the efficacy of products as determined in a specified and well-monitored population is only one aspect of product performance--patient characteristics and behaviour are critical. Observational studies in real-world primary care settings suggest that the choice of inhaler device has an important impact on asthma outcomes. The IMS Mediplus database has now been used to compare outcomes among patients receiving initial maintenance therapy with beclometasone dipropionate administered via different dry powder inhalers. Patients using the DISKHALER dry powder inhaler used significantly less short-acting beta(2)-agonist than those using the ROTAHALER dry powder inhaler. This suggests a difference in the level of asthma control with the different devices, even when the same chemical entity is delivered. Real-world studies suggest, therefore, that outcomes are not always the same with all dry powder inhalers. This indicates the need for further studies to investigate the impact of inhaler device choice and the impact of switching between devices.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchodilator Agents; Humans; Nebulizers and Vaporizers; Powders; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

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

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

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

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

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchial Diseases; Bronchial Hyperreactivity; Bronchitis; Constriction, Pathologic; Drug Therapy, Combination; Eosinophilia; Glucocorticoids; Humans; Salmeterol Xinafoate; Theophylline

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

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

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

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

In 1999, a robust dose-finding study showed that the chlorofluorocarbon (CFC) -free formulation of beclometasone dipropionate (BDP), QVAR (hydrofluoroalkane-134a BDP), produced equivalent asthma control to CFC-BDP at approximately half the daily dose in adults. Since then, a wealth of clinical and pharmaco-vigilance studies have been undertaken to confirm these results and establish dose-potency ratios with other inhaled corticosteroids (ICS). This review summarises the results of studies performed by the manufacturer that have been published since the last comprehensive review of the efficacy and safety of QVAR in 2000. Long-term comparisons with CFC-BDP have confirmed the durability of the 2:1 daily dosing ratio of CFC-BDP:QVAR in adults. Clinical comparisons with other ICS in both symptomatic and asymptomatic patients have established dose-potency ratios of 2: 1 for budesonide:QVAR and 1:1 for fluticasone:QVAR. Furthermore, QVAR has been associated with benefits on asthma symptomatology and quality of life, compared with other ICS that probably arises from its peripheral deposition in the lung.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome; Vital Capacity

Topics: Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Glucocorticoids; Humans; Inflammation Mediators; Leukotriene Antagonists; Leukotrienes; Membrane Proteins; Patient Compliance; Practice Guidelines as Topic; Receptors, Leukotriene; Severity of Illness Index

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

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

Long-term management of asthma includes identification and avoidance of precipitating factors of asthma, pharmacotherapy and home management plan. Common precipitating factors include viral upper respiratory infections, exposure to smoke, dust, cold food and cold air. Avoidance of common precipitating factors has been shown to help in better control of asthma. Pharmacotherapy is the main stay of treatment of asthma. Commonly used drugs for better control of asthma are long and short acting bronchodilators, mast cell stabilizers, inhaled steroids, theophylline and steroid sparing agents. After assessment of severity most appropriate medications are selected. For mild episodic asthma the medications are short acting beta agonists as and when required. For mild persistent asthma: as and when required bronchodilators along with a daily maintenance treatment in form of low dose inhaled steroids or cromolyn or oral theophylline or leukotriene antagonists are required. Moderate persistent asthma should be treated with inhaled steroids along with long acting beta agonists for symptom control. For severe persistent asthma the recommended treatment includes inhaled steroids, long acting beta agonists with or without theophylline. If symptoms are not well controlled, a minimal dose of oral prednisolone preferably on alternate days may be needed in few patients. Patients should be followed up every 8-12 weeks. On each follow up visit patients should be examined by a doctor, compliance to medications should be checked and actual inhalation technique is observed. Depending on the assessment, medications may be decreased or stepped up. For exercise induced bronchoconstriction: cromolyn, short or long acting beta agonists or leukotriene antagonists may be used. In children with seasonal asthma, maintenance treatment according to assessed severity should be started 2 weeks in advance and continued throughout the season. These patients should be reassessed after discontinuing the treatment. Parents should be given a written plan for management of acute exacerbation at home.

Topics: Administration, Inhalation; Albuterol; Allergens; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Cromolyn Sodium; Drug Therapy, Combination; Glucocorticoids; Humans; Immunotherapy; Patient Education as Topic

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

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

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

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

Fear of growth retardation may account for the underuse of inhaled corticosteroids in children with asthma, despite compelling evidence of their effectiveness. This fear may be reduced with newer agents with lower oral bioavailability if their theoretical advantage of fewer systemic adverse effects than the standard treatment of inhaled beclometasone is realized in practice. This review aims to determine if one of the newer agents, inhaled fluticasone, has less effect on the growth of pre-pubertal asthmatic children than inhaled beclometasone. The outcome measure was growth velocity. Two double blind, randomized controlled trials were identified. In one of the studies the mean growth velocity in the fluticasone group was 0.7 cm/year greater than in the beclometasone group. In the second, smaller study the mean growth velocity in the fluticasone group was 0.8 cm/year greater. There is therefore some evidence that fluticasone has less (if any) adverse effect on growth.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Fluticasone; Growth Disorders; Humans

When choosing a drug regimen, physicians can rely on two models: their own clinical experience and results from clinical trials. Both options have problems. Overall, patients with persistent asthma symptoms often have improved outcomes with the use of long-term controller medications on a daily basis to prevent exacerbations of symptoms. Inhaled corticosteroids (ICSs) are generally recognized as being the most effective treatment for the underlying inflammatory characteristics of asthma. However, despite adequate dosing, some patients with persistent asthma remain symptomatic while taking an ICS. Therefore, it may be beneficial to administer combination therapy with an ICS and a long-acting beta-agonist (LABA) in this subset of asthma patients. Another anti-inflammatory choice for persistent asthma is the leukotriene receptor antagonist (LTRA), either as monotherapy or in combination with an ICS. Regardless of what treatment regimen a physician chooses to prescribe, the choice of medication depends on many factors, including patient preference, physician comfort with the regimen, and cost.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

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

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

Beclomethasone dipropionate (BDP) is available in a wide range of daily doses for the treatment of long-term asthma.. To assess the evidence for a dose response relationship for BDP in the treatment of long-term asthma.. We searched the Cochrane Airways Group trial register, Cochrane Controlled Trials Register (The Cochrane Library issue 1 1999) and references lists of articles. Authors and Glaxo Wellcome UK were contacted to identify eligible studies. We also hand searched the proceeding from relevant respiratory society meetings, the British Journal of Clinical Research and the European Journal of Clinical Research for studies.. Prospective, randomised trials comparing two or more daily doses of BDP in patients over the age of two years with long-term asthma.. Trials were selected for inclusion and scored for quality by two reviewers. Data were extracted by one reviewer. Authors were contacted to clarify details of study design and retrieve missing data.. 11 trials involving 1614 subjects were included. Methodological quality was variable. Studies rarely gave a clear indication of the degree of asthma control at baseline. Less than two-fold to five-fold dose differences were assessed by different studies. The results are reported as weighted mean differences (WMD) with 95% confidence limits (95% CI). The number of trials (N) contributing to each outcome is stated. In non-oral steroid treated asthmatics a small advantage of BDP 800 mcg/d over 400 mcg/d was apparent for improvement in morning peak expiratory flow rate (PEFR) compared to baseline, WMD 11 L/min (95% CI 4 to 19 L/min) N=2; improvement in forced expired volume in one second (FEV1) compared to baseline, WMD 9 ml (95% CI 3 to 140) N=1; and reduction in night-time symptom score compared to baseline, WMD 0.13 (95% CI 0.04 to 0.22) N=1. Studies that assessed BDP 1000 v 500 mcg/d and BDP 1600 v 400 mcg/d demonstrated significant advantage of higher dose over lower dose for histamine bronchial hyper-responsiveness (BHR) and percentage improvement in FEV1 compared to baseline. No differences between higher and lower daily doses of BDP were apparent for daytime symptoms, withdrawals due to asthma exacerbation, oropharyngeal side effects or measures of hypothalamo-pituitary-adrenal (HPA) function. No difference in prednisolone sparing effect was apparent when comparing high dose and low dose BDP in oral corticosteroid (OCS) dependent patients.. BDP appears to demonstrate a shallow dose response effect in long-term asthma for a small number of efficacy outcomes over range of daily doses from 400 mcg/d to 1600 mcg/d, although the clinical significance of the improvements afforded by higher doses is questionable.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

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

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

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

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

To evaluate the efficacy and safety of changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate.. Data from 11 randomized, double-blind, parallel-group trials in adults (>= 12 years; n = 1453; % predicted FEV1 = 42% to 89%) and 4 trials in children (4-11 years; n = 161; % predicted FEV1 = 50% to 112%) with chronic asthma were retrospectively analyzed. Symptomatic adults (n = 1181) treated with low-to-medium doses of beclomethasone dipropionate (168-672 mcg/day), triamcinolone acetonide (400-1200 mcg/day), or flunisolide (>=1000 mcg/day) were switched to low-dose fluticasone propionate (176 or 200 mcg daily) for 6-26 weeks. Patients (n = 272) remaining on low-dose beclomethasone dipropionate (336 mcg daily) served as controls. Pediatric patients previously treated with low doses of triamcinolone acetonide (4-8 puffs/day), or low-to-medium doses of beclomethasone dipropionate (4-8 puffs/day) or flunisolide (2-6 puffs/day), were changed to low-dose fluticasone propionate (100 mcg daily) for 12-52 weeks.. Improvements in FEV1, morning and evening peak expiratory flow (PEF), rescue albuterol use, asthma symptom scores, and symptom-free days were significantly greater in adults who changed from low-to-medium doses of beclomethasone dipropionate or triamcinolone acetonide to low-dose fluticasone propionate (P <.001). Regardless of the degree of asthma severity, these improvements were 1.5- to 4-fold greater in adult patients changed to low-dose fluticasone propionate vs those remaining on low-dose beclomethasone dipropionate. Significant improvements in lung function, albuterol use, and asthma symptoms (P <=.002) were also seen in pediatric patients who changed from beclomethasone dipropionate, flunisolide, or triamcinolone acetonide to a much lower dose of an inhaled corticosteroid (100 mcg fluticasone propionate daily). Drug-related adverse events were low in adults and children, and were comparable among adults receiving low-dose fluticasone propionate or beclomethasone dipropionate.. Results indicate that patients with persistent asthma can change from other inhaled corticosteroids to a lower dose of fluticasone propionate and still maintain or improve asthma control.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

Topics: Adolescent; Age Factors; Albuterol; Androstadienes; Anticonvulsants; Asthma; Atovaquone; Attention Deficit Disorder with Hyperactivity; Beclomethasone; Carbamazepine; Child; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Approval; Drug Combinations; Drug Delivery Systems; Drug Therapy; Epilepsies, Partial; Fluticasone-Salmeterol Drug Combination; HIV Protease Inhibitors; Humans; Insulin; Insulin Glargine; Insulin, Long-Acting; Lopinavir; Methylphenidate; Naphthoquinones; Nebulizers and Vaporizers; Oxcarbazepine; Pediatrics; Proguanil; Pyrimidinones; Ritonavir; United States

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

To determine the clinical effectiveness of pressurised metered dose inhalers (with or without spacer) compared with other hand held inhaler devices for the delivery of corticosteroids in stable asthma.. Systematic review of randomised controlled trials.. Cochrane Airways Group trials database (Medline, Embase, Cochrane controlled clinical trials register, and hand searching of 18 relevant journals), pharmaceutical companies, and bibliographies of included trials.. All trials in children or adults with stable asthma that compared a pressurised metered dose inhaler with any other hand held inhaler device delivering the same inhaled corticosteroid.. 24 randomised controlled trials were included. Significant differences were found for forced expiratory volume in one second, morning peak expiratory flow rate, and use of drugs for additional relief with dry powder inhalers. However, either these were within clinically equivalent limits or the differences were not apparent once baseline characteristics had been taken into account. No significant differences were found between pressurised metered dose inhalers and any other hand held inhaler device for the following outcomes: lung function, symptoms, bronchial hyper-reactivity, systemic bioavailability, and use of additional relief bronchodilators.. No evidence was found that alternative inhaler devices (dry powder inhalers, breath actuated pressurised metered dose inhalers, or hydrofluoroalkane pressurised metered dose inhalers) are more effective than the pressurised metered dose inhalers for delivery of inhaled corticosteroids. Pressurised metered dose inhalers remain the most cost effective first line delivery devices.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Candidiasis, Oral; Child; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome

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

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

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

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

Asthma has been recognized as a chronic inflammatory disorder of the airway. The early use of antiinflammatory agents, one of which is inhaled corticosteroids, is advocated in the treatment of chronic asthma. Beclomethasone dipropionate (BDP) is effective in childhood asthma. CD4 T-cell activation correlate with the values of the coefficient variation (CV) of peak expiratory flow (PEF) in asthmatic patients, suggesting that CV of PEF is a good marker for assessing not only the variability of airway obstruction but also the degree of airway inflammation. PEF monitoring is useful for better controlling asthma, because some patients treated with inhaled corticosteroid may still remain undertreated.

Topics: Administration, Inhalation; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; CD4-Positive T-Lymphocytes; Child; Chronic Disease; Cromolyn Sodium; Humans; Lymphocyte Activation; Monitoring, Physiologic; Peak Expiratory Flow Rate

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Chronic Disease; Drug Therapy, Combination; Glucocorticoids; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Randomized Controlled Trials as Topic; Sulfonamides; Tosyl Compounds

The understanding of the damaging effect of chlorofluorocarbons (CFCs) on the stratospheric ozone has led to international agreements calling for the total phase-out of CFC production. The banning of CFCs in pressurized metered dose inhalers used in airways disorders has been postponed on a temporary basis until replacement propellants have been identified. Hydrofluoroalkanes HFA-134a and HFA-227 have been shown to have no ozone damaging potential and to be safe. However, HFAs cannot simply be substituted for CFCs in inhalers of identical design. Their use has required changes in many aspects of the drug formulation, inhaler design and manufacture. This, in turn, has provided at least to some pharmaceutical companies an opportunity to assess and enhance the performances of new inhalers. The new products are neither technically nor pharmacologically identical to their CFC-based counterparts. Some of them have now completed clinical trials and the transition has already started: by the end of 1998, 2 short acting beta-agonist HFA-based inhalers and a corticosteroid HFA-based inhaler have reached the marketplace in France.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aerosol Propellants; Animals; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chlorofluorocarbons; Humans; Hydrocarbons, Fluorinated; Respiratory Therapy

Inhaled steroids play a central role in the management of childhood asthma. There is concern about their side effects, especially on growth. However asthma may also cause growth retardation. Growth rates are not stable, so randomised controlled parallel group studies are needed to assess the impact of inhaled steroids on growth. This review is confine to one inhaled steroid, beclomethasone, that is known to have significant levels of systemic absorption.. To determine whether inhaled beclomethasone cause significant delay in the linear growth of children with asthma.. The Cochrane Airways Group asthma register was searched. Bibliographies from included studies, and known reviews were searched for additional citations. Personal contact with colleagues and researchers working in the field of asthma were made to identify potentially relevant trials.. Randomized, controlled trials comparing the effects of beclamethasone to non-steroidal medication (placebo or non-steroidal therapy) on the linear growth of children with asthma.. Data related to the clinical outcome "change in growth" were extracted by two reviewers working independently. One hundred and fifty-nine citations were identified by the search strategy and bibliography review. Three studies met the inclusion criteria. All used beclomethasone 200 mcg twice daily delivered by dry powder Diskhaler to treat children with mild-moderate asthma. Study duration was 7-12 months. In all three studies, a significant decrease in linear growth occurred in children treated with beclomethasone compared to those receiving placebo or non-steroidal asthma therapy. The average decrease, calculated through meta-analysis, was -1.54 cm per year (95% CI -1.15, -1.94).. In children with mild-moderate asthma, beclomethasone 200 mcg twice daily caused a decrease in linear growth of -1.54 cm per year. These studies lasted a maximum of 54 weeks, so it remains unclear whether the decrease in growth is sustained or whether it reverses with 'catch up' after therapy is discontinued. We are unable to comment on growth effects of other inhaled steroids that have potentially less systemic effects. If inhaled steroids are required to control a child's asthma, we recommend using the minimum dose that effectively controls the child's asthma and closely following growth.

Topics: Age Factors; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child Development; Growth; Humans

To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids.. Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses.. EMBASE, Medline, and GlaxoWellcome internal clinical study registers.. Efficacy and exacerbations.. Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of >/=12 weeks with 3685 symptomatic patients aged >/=12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids, in patients receiving salmeterol morning peak expiratory flow was greater at three months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min, P<0.001) and six months (27.7 (19.0 to 36.4) litre/min, P<0.001). Forced expiratory volume in one second (FEV(1)) was also increased at three months (0.10 (0.04 to 0.16) litres, P<0.001) and six months (0.08 (0.02 to 0.14) litres, P<0.01), as were mean percentage of days and nights without symptoms (three months: days-12% (9% to 15%), nights-5% (3% to 7%); six months: days-15% (12% to 18%), nights-5% (3% to 7%); all P<0.001) and mean percentage of days and nights without need for rescue treatment (three months: days-17% (14% to 20%), nights-9% (7% to 11%); six months: days-20% (17 to 23%), nights-8% (6% to 11%); all P<0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P=0. 02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P=0.03).. Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days and nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.

Topics: Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Drug Administration Schedule; Drug Therapy, Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

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

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

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

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

Topics: Administration, Topical; Aerosol Propellants; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Glucocorticoids; Humans; Hydrocarbons, Fluorinated

As has been discussed in the previous sections of the Supplement, the improved physical characteristics of HFA-BDP extrafine aerosol spray allow BDP to be delivered more efficiently into the large, medium and small airways. This improved delivery has allowed the dose of HFA-BDP to be reduced compared to CFC-BDP and budesonide, whilst maintaining equipotency with fluticasone. However, unlike fluticasone, HFA-BDP does not show a propensity for blood or tissue accumulation when administered with a 12-h dosing interval. Standard tests for assessing effects on the HPA-axis indicate that HFA-BDP extrafine aerosol has a favourable systemic bioactivity profile. Even up to the recommended dose of 800 microg day(-1) HFA-BDP (the highest recommended maximum dose), there appear to be no clinically relevant systemic side effects associated with HFA-BDP (Fig. 8). Thus, viewing the data as a whole, it would seem that, compared to CFC-BDP and alternative inhaled corticosteroids, HFA-BDP in a dose of up to 800 microg day(-1) exhibits a favourable therapeutic ratio.

Topics: Administration, Topical; Aerosol Propellants; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Risk Assessment

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

Topics: Administration, Topical; Aerosol Propellants; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchography; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Tomography, X-Ray Computed

Topics: Administration, Topical; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated

Inhaled beclomethasone diproprionate (BDP) has been, together with inhaled budesonide, the mainstay of anti-inflammatory therapy for asthma for many years. A range of new prophylactic therapies for asthma is becoming available and BDP is now frequently used as the reference treatment against which these newer agents are being compared.. The objectives of this review were to: a) Compare the efficacy of BDP with placebo in the treatment of chronic asthma. b) Explore the possibility that a dose response relationship exists for BDP in the treatment of chronic asthma. c) To provide the best estimate of the efficacy of BDP as a benchmark for evaluation of newer asthma therapies.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and Glaxo Wellcome for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing BDP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager (Revman) 4.0.3 with Metaview 3.1.. 52 studies were selected for inclusion (3459 subjects). The studies were generally of high methodological quality. In non-oral steroid treated patients, BDP produced significant improvements in a number of efficacy measures compared to placebo including FEV1 weighted mean difference (WMD) 340ml (95% CI 190-500ml); FEV1 (% predicted) WMD 6% (95% CI 0.4 to 11.5%) and morning PEFR WMD 50 L/min (95% CI 8 to 92 L/min). BDP also led to reductions in rescue beta2 agonist use compared to placebo WMD 1.75 puffs/d (95% CI 1.4 to 2.4 puffs/d) and reduced the likelihood of trial withdrawal due to asthma exacerbation relative risk (RR) 0.26 (95% CI 0.15 to 0.43). In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD 5 mg/d (95% CI 4 to 6 mg/d) and a higher likelihood of discontinuing oral prednisolone RR 0.54 (95% CI 0.43 to 0.67). There was little evidence for a clincially worthwhile dose response effect, but few studies recruited patients with more severe asthma.. This review has quantified the efficacy of BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in patients with severe disease.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic

BRONCHIAL INFLAMMATION AND GLUCOCORTICOIDS: Bronchial inflammation plays an important role in asthma and contributes to bronchoconstriction, hypersecretion and bronchial hyperreactivity. Glucocorticoids are the gold standard treatment in asthma affecting most of the components involved in bronchial inflammation. Inhaled steroids are recommended early in most countries.. The molecular and cellular mechanisms of glucocorticoids action are still better understood. However, it remains difficult to evaluate individual sensitivity when initiating treatment. Glucocorticoids have an effect on all inflammatory cells and bronchial structure cells. They bind to cytoplasmic receptors and then the complex links to DNA, inducing or inhibiting gene transcription in the target cell. DIFFERENT GLUCOCORTICOID SENSITIVITY: Very few patients are totally insensitive to the effect of glucocorticoids and require specific explorations for an identification. Although individual variability in corticosensitivity is similar in asthmatic patients and in the general population, the underlying mechanisms remain to be fully elucidated. The difference observed between responders and non-responders is not clearly identified and their definitions must be fully adapted.

Topics: Administration, Inhalation; Administration, Topical; Adrenal Cortex Hormones; Adult; Age Factors; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Child; Glucocorticoids; Humans; Maximal Expiratory Flow-Volume Curves; Receptors, Glucocorticoid

Chlorofluorocarbon (CFC)-containing inhalers are gradually being phased out and replaced with hydrofluoroalkane (HFA)-based alternatives. The reformulation provided the opportunity to improve the inhalation technology and physical characteristics of corticosteroid formulations. QVAR contains HFA-beclomethasone dipropionate (HFA-BDP) with the steroid in solution rather than suspension, which, in combination with improved inhaler technology, produces an extrafine aerosol with a mass median aerodynamic diameter of 1.1 microm (smaller than the 3.5-4.0 microm found with CFC-BDP). It was predicted and demonstrated that the smaller particle size of QVAR would be deposited in the lung to a greater extent than that found with CFC-BDP, particularly in the small airway, a major site of inflammation. Increased lung deposition of QVAR permits a reduction in dosage relative to CFC-BDP. Clinical evidence confirms that adult and elderly patients required approximately half the dose of QVAR to achieve the same degree of asthma control as with CFC-BDP. In long-term assessments, patients taking CFC-BDP could be switched to QVAR at half the daily dose without exacerbation of their asthma symptoms. QVAR was associated with a low overall incidence of side effects and, at the maximum recommended dose of 640 microg/d, caused no more adrenal suppression than 672 microg/d CFC-BDP.

Topics: Administration, Inhalation; Aerosol Propellants; Aerosols; Asthma; Beclomethasone; Humans; Hydrocarbons, Fluorinated; Therapeutic Equivalency

In 1997, the National Heart, Lung, and Blood Institute released the Second Expert Panel Report on the Guidelines for the Diagnosis and Management of Asthma as a follow-up to the first report issued in 1991. Implementation of the recommendations from this report could have a potentially huge impact on care and treatment of asthma in the United States. Even though the Guidelines are expansive, there are some areas related to the pharmacologic component that warrant further discussion and clarification. These are: (1) safety and efficacy of available asthma medications, (2) clinical efficacy comparisons of inhaled corticosteroids, (3) comparative risks among inhaled corticosteroids, and (4) expectations of different delivery systems used with inhaled corticosteroids.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Therapy, Combination; Humans; United States

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Steroids

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

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

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

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

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

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

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

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

Topics: Administration, Inhalation; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cromolyn Sodium; Delayed-Action Preparations; Humans; Monitoring, Physiologic; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Practice Guidelines as Topic; Theophylline

The reformulation of asthma medications with non-ozone depleting propellants such as hydrofluoroalkane-134a (HFA) has provided the opportunity to apply new knowledge and inhaler technology to improve significantly the delivery of aerosol drugs to the respiratory tract. Beclomethasone dipropionate (BDP), the most commonly prescribed inhaled corticosteroid for asthma therapy, is effective therapy; however currently available chlorofluorocarbon (CFC)-BDP metered dose inhalers typically deliver no more than 10% of the inhaled drug to the lungs with the remainder deposited in the oropharynx. Compared with an average particle size of 3.5-4.0 microns for CFC-BDP, the new HFA-BDP formulation has an average particle size of 1.1 microns and a respirable fraction of approximately 60%. The lung deposition of 99mTc-radiolabelled HFA-BDP has been investigated in healthy volunteers and patients with asthma. Results showed that the HFA-BDP formulation reverses the pattern of distribution seen with CFC-BDP products, delivering most of the dose of inhaled steroid directly to the lungs rather than to the oropharynx and gut where it may lead to unwanted side-effects. As such, HFA-BDP is likely to achieve equivalent efficacy to existing CFC-BDP formulations with lower doses and with reduced potential for local adverse effects.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Drug Delivery Systems; Humans; Hydrocarbons, Fluorinated; Lung; Nebulizers and Vaporizers; Particle Size; Pulmonary Alveoli; Radionuclide Imaging; Technetium

Reformulation of beclomethasone dipropionate (BDP) in the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane-134a (HFA) gave the opportunity to produce a solution formulation that provides a greater total mass of fine drug particles than the current CFC suspension metered dose inhaler (MDI). The HFA-BDP MDI was studied in three pharmacokinetic trials in asthmatic patients. Serum levels of BDP plus metabolites [total beclomethasone (total BOH) assay] were used to test whether the increased fine particle mass of HFA-BDP would result in improved intrapulmonary deposition and subsequent differences in serum profiles. Serum levels, maximum serum concentrations and area under the serum concentration-time curves of total BOH following both single and multiple doses of HFA-BDP were similar to those obtained with approximately twice the dose of CFC-BDP. The observed lower bioavailability of CFC-BDP compared with HFA-BDP could be explained if most of each inhaled dose from the CFC-BDP MDI was swallowed and absorbed from the gastrointestinal tract, while most of each inhaled dose from the HFA-BDP MDI was absorbed from the lungs. Deposition studies have confirmed this explanation. These results suggest that asthmatic patients can be treated with lower total daily doses of drug from HFA-BDP extrafine aerosol than from CFC-BDP.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Hydrocarbons, Fluorinated; Lung; Male; Middle Aged; Particle Size; Randomized Controlled Trials as Topic

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

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

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

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

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

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

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Infant; Severity of Illness Index

Asthma is a disease of the entire respiratory tract and successful asthma therapy requires drug delivery throughout the large and small airways. The most commonly prescribed inhaled corticosteroid for the treatment of asthma is beclomethasone dipropionate (BDP) delivered by a metered-dose inhaler (MDI) containing chlorofluorocarbons (CFCs). CFC-BDP MDIs produce relatively large particles and when used optimally deposit less than 10% of the dose in the lungs, primarily in the large airways, with more than 90% being deposited in the oropharynx. The new hydrofluoroalkane (HFA)-BDP inhaler developed by 3M Pharmaceuticals (Qvar) delivers a particle size of approximately 1.1 microns. Animal and mechanical models predict more than 50% lung deposition with this formulation. Clinical results, with radiolabelled Qvar in patients with asthma and volunteers, have demonstrated that 50-60% of the dose is deposited throughout the airways with approximately 30% being deposited in the oropharynx. 3M Pharmaceuticals have developed the breath-actuated Autohaler which provides the same lung deposition as an optimally used Qvar MDI by automatically delivering the drug very early in the inhalation. Neither device routinely requires the use of a spacer.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Humans; Nebulizers and Vaporizers; Steroids

The reformulation of beclomethasone dipropionate (BDP) in a chlorofluorocarbon (CFC)-free propellant, hydrofluoroalkane (HFA), has resulted in improved delivery of medication to the large and small airways, the target site of action of anti-asthmatic therapy. It is hypothesised that this improved delivery of BDP to the airways will translate into improved clinical efficacy in comparison with the previous CFC formulation. This paper reviews the results of three large-scale clinical trials that were designed to test this hypothesis by comparing the efficacy of various doses of Qvar (3M Pharmaceuticals' HFA-BDP formulation) with CFC-BDP in asthmatic patients. It was found that the dose-response relationship of Qvar is shifted to the left compared with CFC-BDP, such that equivalent improvements in asthma control are seen with half the daily dose of Qvar compared with the CFC formulation.

Topics: Administration, Inhalation; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Delivery Systems; Humans

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

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

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Administration Schedule; Humans; Practice Guidelines as Topic; Steroids

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

Topics: Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Beclomethasone; Betamethasone; Bronchodilator Agents; Humans; Isoproterenol; Peak Expiratory Flow Rate; Prednisolone; Theophylline

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Humans

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

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

Recently, bronchial asthma has been widely recognized as a chronic inflammatory disorder of the airways. In the course of inflammation, many kinds of inflammatory cells such as lymphocytes, especially Th2 lymphocytes, mast cells, eosinophills, bronchial epithelial cells interact each other by so-called cytokine network. Bronchial hyperreactivity, which is a characteristic phenomenon in bronchial asthma, is induced as a result of bronchial inflammation. According to the inflammation theory of pathogenesis of bronchial asthma, anti-inflammatory treatment using inhaled corticosteroid is recommended as the first choice of asthma therapy. Bronchial biopsy proved decrease of the number of infiltrating inflammatory cells such as T lymphocytes, eosinophils and mast cells in the bronchial submucosal tissue after inhaled steroid treatment. Improvement of bronchial reactivity after inhaled steroid therapy was also reported. Recently, a certain group of so-called steroid resistant asthma has been known and the mechanism of it is now under investigation.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchial Diseases; Bronchial Hyperreactivity; Cytokines; Eosinophils; Humans; Inflammation; Inflammation Mediators; Mast Cells; T-Lymphocytes

Bronchial asthma is no longer considered a condition with isolated, acute episodes of bronchoconstriction. Rather, asthma is now understood to be a chronic inflammatory disorder of the airways. Therefore anti-inflammatory agents and, more specifically, inhaled corticosteroids are at present the most effective controllers in long-term treatment and prevention of asthma. Asthma is highly variable, so precise classification of severity is needed for management. Asthma therapy recommended in guidelines follows a stepwise approach in which the level of therapy is increased (step up) as the severity of asthma increased and therapy decreased (step down) once control is achieved and sustained. In this stepwise approach, inhaled corticosteroid is a key drug and establishment of the dosage of inhaled corticosteroid is most important.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Japan; Practice Guidelines as Topic; Severity of Illness Index; Societies, Medical; World Health Organization

In 1988, we started to change our treatment policy, away from a polypharmaceutical approach including oral bronchodilators and oral anti-allergic agents available in Japan, toward an inhalation therapy including inhaled corticosteroids and inhaled beta-agonist. A marked decline in the number of asthma admission and death from asthma started coincidentally with the increased use of inhaled corticosteroid which were followed by the decreased use of inhaled beta-agonists and oral anti-asthma agents. The intensification of patient education mainly consisting of emphasizing on better understanding of benefits of inhalation therapy and a self-management is likely to play an important role in enhancing a protective effects of inhaled corticosteroids. Despite some limitations of inhaled corticosteroids, such as poorer dose response in elderly asthmatics and/or patients with severe disease, further introduction of guide-line treatment will result in a measurable improvement on asthma control.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Humans; Patient Education as Topic; Quality of Life; Self Administration

Inhaled steroid therapy has become a most popular anti-inflammatory medication in asthmatic children. However, overreliance on inhaled steroids should not mislead the treatment of asthma because the best way to prevent asthmatic symptoms is the identification and control of triggers such as allergens and non-specific irritants. We should weigh the merits against adverse effects and make a correct decision to use inhaled steroids in each asthmatic child. Since the effectiveness of inhaled steroids mainly depends on the correct performance of inhalation therapy, we must educate patients and their family to develop a good partnership in asthma management as emphasized in every guideline.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Family; Female; Humans; Male; Patient Education as Topic

Our data indicate that 1800 micrograms of per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe asthma in adults whose symptoms are not controlled with the combination of 800 approximately 900 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of inhaled steroid is more useful and should be promptly began to treat severe asthma. Oral steroid therapy for long-term management should be introduced to mostly severe case after high dose inhaled BDP therapy reveals to be failure.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate

Effects and actions of DSCG and corticosteroids in the airways could not essentially evaluated at the same situation, before the inhaled BDP had been used. Each of the drugs have been shown to reduce both immediate and late phase responses in experimentally induced asthma, exercise induced bronchospasm, and bronchial hypersensitivity to histamine especially after the prolonged pretreatment of BDP. DSCG probably targets nonspecifically the surfaces of relevant cells including mast cells and eosinophils, but BDP are known to act specifically and/or nonspecifically on the gene transcription in the various types of cells including eosinophils, lymphocytes, and resident cells. Many informations on the systemic side effects of BDP will be still required.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cromolyn Sodium; Eosinophils; Humans; Inflammation Mediators; Mast Cells; Transcription, Genetic

Inhalation of disodium clomoglycate (DSCG) is main therapy for childhood asthma in Japan. Regular inhalation of both DSCG and beta 2 stimulant is recommended for the treatment of severe asthma in the guideline which was made in 1993. Characteristic of childhood asthma such as retardation of growth and exercise-induced asthma is considered as an important view point in Japanese pediatric field. On the other hand inhalation of beclomethasone dipropionate (BDP) is used for the treatment of adult-hood asthma in Japan and WHO global storategy. In the future new treatment will be developed using both DSCG and BDP.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Age of Onset; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Child; Cromolyn Sodium; Drug Combinations; Humans

Treatment with inhaled steroid has become increasingly important in asthma. However there are also many patients with asthma whose symptoms are uncontrolled by beclomethasone dipropionate (BDP) alone. For these patients we have tried the regular use of inhaled procaterol or inhaled fenoterol with BDP, and some of these patients have got good control. Recent studies show that, in patients whose asthma is inadequately controlled with BDP, better control can be achieved by adding inhaled long-acting beta 2-agonist rather than by doubling the dose of BDP. In the near future inhaled long-acting beta 2-agonist will be possible for clinical use in our country, and the combined use of it and BDP as preventive therapy will be the mainstay of treatment for patients with moderate-to-severe asthma.

Topics: Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Fenoterol; Humans; Procaterol

Topics: Adrenergic beta-Agonists; Asthma; Beclomethasone; Bronchodilator Agents; Child; Clinical Trials as Topic; Cromolyn Sodium; Humans; Metaproterenol; Randomized Controlled Trials as Topic; Theophylline

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

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

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

This analysis summarizes studies comparing attained heights with expected heights of children with asthma treated with inhaled or oral corticosteroids. The possible moderating effects of treatment duration, and dosage and asthma severity are also examined. A preliminary database of 95 articles rendered 21 includable studies representing 810 patients with asthma, which yielded 29 tests of the corticosteroid-growth effect. Statistical integration of the results of these studies revealed a significant but small tendency for corticosteroid therapy in general to be associated with diminished final height (Z = 2.328, p = 0.01, mean r = -0.023). However, this effect varied for the specific drugs under consideration. As expected, significant weak growth impairment was observed for prednisone (Z = 2.137, p = 0.0164, mean r = -0.295) and "other oral corticosteroids" (Z = 9.107, p = 2.44E-18, mean r = -0.260). On the other hand, a significant moderate tendency was observed for inhaled beclomethansone dipropionate therapy to be associated with attaining normal stature (Z = 7.395, p = 2.17E-13, mean r = +0.432). There was no statistical evidence for beclomethasone dipropionate therapy to be associated with growth impairment at higher doses, for longer therapy durations, or among patients with more severe asthma. This meta-analytic integration indicates that available studies of inhaled beclomethasone dipropionate therapy do not show an association between its use and the adverse effect of diminished stature.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Age Factors; Asthma; Beclomethasone; Child; Growth; Humans

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

Corticosteroid inhibits airway inflammation associated with eosinophils and lymphocytes in bronchial asthma. Asthma severity is classified according to symptoms, airflow obstruction (PEF) and treatment requirement. Step 1: A patient has mild asthma. Inhaled corticosteroid, beclomethasone dipropionate (BDP), is used not to exceed 200 micrograms a day. Step 2: A patient has moderate asthma. The primary therapy is 200-400 micrograms of BDP a day. Step 3: If the patient experiences exacerbations, 400 to 1000 micrograms of BDP a day are required. Step 4: A patient has severe asthma. Oral corticosteroid and/or 800-1600 micrograms of BDP are available. Intravenous corticosteroid therapy for acute exacerbation of asthma is applied for patients who have moderate or severe exacerbation. Corticosteroids are currently the most effective anti-inflammatory drugs for the treatment of asthma. Corticosteroids, however, have many sort of adverse effects. Adverse effects of inhaled corticosteroids are less than those of oral corticosteroid except for local effects. Use of spacer and gargle after the inhalation are recommended to reduce the local adverse effects.

Topics: Administration, Inhalation; Administration, Oral; Asthma; Beclomethasone; Glucocorticoids; Humans; Injections, Intravenous; Prednisolone

The treatment of asthma has undergone dramatic changes in the past two decades. These changes stem from the marked increase in our understanding of the pathophysiology of asthma as well as from the availability of potent and effective therapeutic agents. This review discusses the current treatment of asthma considered from a pathophysiologic perspective, focusing on the roles of specific and symptomatic approaches. Specific therapies are aimed at the underlying processes causing asthma, with the goal of reducing symptoms and the need for concomitant medication. Choices include allergen avoidance, immunotherapy, inhaled cromolyn or nedocromil, and inhaled or oral corticosteroids. Symptomatic therapies that control the symptoms of asthma without affecting the underlying causes are used alone or to provide coverage in the period before specific therapies take effect. Here the options are beta agonists, theophylline, and anticholinergic agents. This article weighs the advantages and disadvantages of each of the principal therapies and discusses today's major controversies, including the link between beta-agonist use and asthmatic deaths, theophylline toxicity, and the efficacy of immunotherapy.

Topics: Albuterol; Asthma; Beclomethasone; Humans

Beclomethasone dipropionate has now been used for more than 10 years during which our knowledge of how to use inhaled corticosteroids has gradually improved: high dose initial treatment followed by progressive reduction down to the minimum effective dosage; administration in 2 daily doses when the asthma is stable and 4 daily doses in case of instability; mild and transient undesirable effects, often minimized by a correct use of the inhaler; effectiveness assessed from bronchial hyper-reactivity and respiratory function tests, reduction or avoidance of oral corticosteroid therapy, or results of association with other treatments, and in particular bronchodilators. When exactly should inhaled corticosteroid therapy should be started and how long should it be pursued are controversial points, but an early and prolonged treatment must probably be recommended.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Candidiasis, Oral; Drug Therapy, Combination; Humans; Pituitary-Adrenal System

Over an 18-month period 31 patients (27 female and 4 male) were referred to the ENT department of our clinic for a 1-month to 14-year history of isolated non-productive cough. As ENT examination, including posterior rhinoscopy, was normal, these patients were sent to the pneumology department. Physical examination and X-ray films of the chest were negative, and the patients did not take an angiotensin converting enzyme inhibitor that could have induced this cough. Inhalation of acetylcholine lowered vital capacity by 32 +/- 14% and forced expiratory volume by 34 +/- 16%, a test which is the hallmark of bronchial hyperreactivity. Three patients were atopic. We believe that this cough can be the only manifestation of bronchial asthma. In these patients, cough was suppressed or strongly attenuated by the inhalation, 5 times a day, of salbutamol 200 mg puffs and beclomethasone dipropionate 250 mcg. In addition, the atopic patients were prescribed 10 puffs of sodium cromoglycate per day. Complaints of isolated non-productive cough must always suggest that possibility of bronchial asthma, and a bronchial provocation test must be performed to confirm this diagnosis.

Topics: Adolescent; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Chronic Disease; Cough; Cromolyn Sodium; Female; Humans; Hypersensitivity, Immediate; Male; Middle Aged

Topics: Allergens; Animals; Asthma; Beclomethasone; Bronchodilator Agents; Chronic Disease; Histamine Antagonists; Humans

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

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

Reports of corticosteroid sensitivity reactions are rare in the medical literature. We report an anaphylactoid reaction to hydrocortisone sodium succinate given intravenously which occurred on two occasions during treatment of a patient for asthma. Intradermal testing with a wide range of steroid preparations gave positive results with hydrocortisone sodium succinate, methylprednisolone sodium succinate, methylprednisolone sodium succinate and methylprednisolone acetate. No reactions occurred to dexamethasone sodium phosphate administered intravenously, prednisolone given orally or beclomethasone dipropionate by inhalation. Results of a radioallergosorbent test (RAST) were negative for hydrocortisone sodium succinate.

Topics: Administration, Inhalation; Adult; Anaphylaxis; Asthma; Beclomethasone; Dexamethasone; Humans; Hydrocortisone; Injections, Intravenous; Intradermal Tests; Male; Recurrence; Skin Tests

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

Forty-five patients with severe, poorly controlled asthma, including 23 corticosteroid-dependent patients, were treated with a preparation of beclomethasone dipropionate aerosol delivering 250 mcg per puff. The daily dose ranged from 1000 to 2000 mcg. The mean follow-up period was 14 +/- 7 months, and 11 patients have now been followed up for more than 2 years. Forty-two patients were improved, and total withdrawal of continuous steroid therapy could be achieved in 13 cases. Treatment remained effective in long term use, provided a minimum of 1000 mcg/day was given. However, despite clinical improvement the obstructive syndrome persisted in 65% of the patients.

Topics: Administration, Inhalation; Aerosols; Asthma; Beclomethasone; Female; Humans; Male; Middle Aged; Time Factors

The effects of high-dose inhaled beclomethasone dipropionate were studied retrospectively in 123 asthma patients who were inadequately controlled on standard doses of beclomethasone dipropionate, or who required oral corticosteroids to control their asthma. High-dose beclomethasone dipropionate was administered by aerosol which delivered 250 micrograms beclomethasone dipropionate per metered dose. Thirty-one percent of the steroid-dependent patients (n = 65) were able to stop maintenance oral steroid after the introduction of beclomethasone dipropionate 250 and a further 48% were able to reduce their daily dosage. The mean reduction in daily maintenance prednisone was 5.2 mg. Comparing a six month period before and during treatment with beclomethasone dipropionate 250, asthma control was improved in 69% of all patients. This was accompanied by a 53% reduction in the number of acute attacks requiring supplementary courses of oral corticosteroid and a 70% reduction in admissions to hospital. Prior to beclomethasone dipropionate 250, 21% of the steroid-dependent patients were maintained on alternate day prednisone whereas after the introduction of beclomethasone dipropionate 250, 44% of those 45 still requiring continuous prednisone were maintained on an alternate-day regimen.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Drug Evaluation; Female; Humans; Male; Middle Aged; Prednisone; Retrospective Studies; Substance-Related Disorders

Topics: Adrenergic Agonists; Aerosols; Asthma; Beclomethasone; Bronchodilator Agents; Humans; Parasympatholytics; Prednisone; Sympathomimetics

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Child; Female; Glucocorticoids; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications

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

Topics: Administration, Intranasal; Administration, Oral; Adult; Aerosols; Animals; Asthma; Beclomethasone; Betamethasone; Betamethasone Valerate; Child; Dogs; Female; Humans; Prednisolone; Pregnancy

Asthma often, but not always, is the result of an IgE-mediated allergic reaction to an airborne antigen. The chain of biochemical reactions is now fairly well defined. These reactions generate an immediate smooth muscle bronchoconstriction and a late inflammation 4 to 24 hours later. This article describes the most important allergens in the community, home and workplace, and discusses procedures for diagnosis and management.

Topics: Allergens; Antigens; Asthma; Beclomethasone; Bronchial Provocation Tests; Cromolyn Sodium; Desensitization, Immunologic; Histamine Release; Humans; Immunoglobulin E; Skin Tests

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

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

Inhaled beclomethasone dipropionate is now well established in the management of asthma. Studies conducted over the last decade, and since the drug was previously reviewed in the Journal, have confirmed that inhaled beclomethasone dipropionate 400 to 800 micrograms daily can reduce the need for oral maintenance corticosteroids in the majority of asthmatic patients requiring such therapy, and that increasing the dosage to 2000 micrograms daily may provide additional clinical benefit in some patients unresponsive to usual therapeutic dosages. Follow-up over a period of several years has confirmed that the initial response to inhaled beclomethasone can be maintained in most patients. Recent studies indicate that beclomethasone dipropionate 400 micrograms daily is equally effective when administered in 2 or 4 divided doses in patients with stable asthma, but it is likely that the lower frequency of administration will be less effective when the asthma is unstable. Recent studies have established the usefulness and good tolerability of intranasal beclomethasone dipropionate in the treatment of perennial and seasonal rhinitis, where the drug has been shown to be more effective than intranasal sodium cromoglycate and similar in efficacy to flunisolide. Nasal polyps decrease in size during continuous treatment with intranasal beclomethasone dipropionate, but enlarge again during periods of respiratory infection. After a decade of treatment with inhaled and intranasal beclomethasone dipropionate, there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Thus, the initial promise of beclomethasone dipropionate has been fulfilled. It has had an important role in asthma therapy over the past decade, which will continue into the future.

Topics: Adrenal Glands; Aerosols; Asthma; Beclomethasone; Bronchi; Drug Therapy, Combination; Glucocorticoids; Humans; Immunity; Kinetics; Nasal Mucosa; Rhinitis

Topics: Administration, Topical; Aerosols; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Asthma; Beclomethasone; Dexamethasone; Fluprednisolone; Glucocorticoids; Humans; Hydrocortisone; Injections, Intra-Articular; Prednisolone; Rhinitis; Skin Diseases; Triamcinolone Acetonide

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Hydroxycorticosteroids

Asthma is defined as an obstructive disease of the pulmonary airways resulting from spasm of airway muscle, increased mucus secretion, and inflammation. The airways of asthmatic individuals are hyperresponsive to a variety of stimuli including cold air, atmospheric irritants, pharmacologically active chemicals, various drugs, and hyperventilation. The fundamental abnormality underlying the hyperresponsiveness appears to be genetically determined; two theories explaining the abnormality have received the most attention. One theory suggests that asthma is due to abnormal beta-adrenergic receptor-adenylate cyclase function with decreased adrenergic responsiveness. An alternate theory proposes that increased cholinergic activity in the airway is the fundamental defect in the disease. The true prevalence of asthma has been difficult to determine owing to uncertainties regarding the definition of the disease. Prevalence in various populations of children ranged from 1.37% to 11.4% or higher. Most studies report a preponderance of asthma in boys over girls, with ratios varying from 1.3:1 to 3.3:1. Risk factors for the disease include a history of atopy, acute lower respiratory tract disease, parental cigarette smoking, and bronchiolitis or croup. The spectrum of asthma is that of an illness beginning early in life and persisting, in some cases, through adulthood. Signs of the disease may be apparent in the first 2 yr of life and are often associated with viral respiratory infections. Disproportionate narrowing of peripheral airways and decreased static elastic recoil properties of the lung predispose infants and young children to asthma. During midchildhood there is a tendency toward improvement, with continued improvement during adolescence. The goal of management of the child with asthma is to reduce symptoms sufficiently so that the child can regularly attend school, engage in play activities, and sleep through the night uninterrupted, while avoiding unacceptable levels of adverse drug effects. Nonpharmacologic management includes both avoidance of environmental irritants and behavioral approaches to overcome emotional precipitants that lead to attacks. Pharmacologic treatment includes the use of four classes of drugs: (1) adrenergics, (2) theophylline, (3) cromolyn, and (4) corticosteroids. The prognosis of asthma in childhood is good. Although airway activity may remain abnormal for indefinite periods of time, most children reach a state where they are virt

Topics: Adolescent; Asthma; Beclomethasone; Behavior Therapy; Child; Child, Preschool; Cromolyn Sodium; Epinephrine; Humans; Prednisolone; Prednisone; Prognosis; Risk; Terbutaline; Theophylline; Tobacco Smoke Pollution

Topics: Albuterol; Asthma; Asthma, Exercise-Induced; Atropine Derivatives; Beclomethasone; Child; Cromolyn Sodium; Humans; Ipratropium; Male

From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Cataract; Cushing Syndrome; Humans; Hypersensitivity; Hypersensitivity, Immediate; Long-Term Care; Nasal Polyps; Osteonecrosis; Osteoporosis; Prednisone; Rhinitis; Sleep Initiation and Maintenance Disorders; Stress, Physiological

Topics: Administration, Oral; Aerosols; Asthma; Beclomethasone; Cortisone; Cromolyn Sodium; Drug Administration Schedule; Glucocorticoids; Humans; Prednisolone; Theophylline

Topics: Adult; Aerosols; Asthma; Beclomethasone; Bronchitis; Child; Clinical Trials as Topic; Double-Blind Method; Humans; Placebos; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal; Time Factors

Topics: Asthma; Atropine; Beclomethasone; Cromolyn Sodium; Humans; Isoproterenol; Metaproterenol; Receptors, Adrenergic, beta; Terbutaline; Theophylline; Triamcinolone Acetonide

The selective beta-2 adrenergic bronchodilator preparations should be considered the medications for the first line of defense in the treatment of the average asthmatic patient. Theophylline and derivatives of theophylline are the second line of defense. Cromolyn sodium, atropine and derivatives, corticosteroids and other selected agents follow, depending on the individual case and the circumstances involved.

Topics: Adrenal Cortex Hormones; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Aminophylline; Asthma; Atropine; Beclomethasone; Bronchodilator Agents; Cromolyn Sodium; Epinephrine; Humans; Ipratropium; Isoproterenol; Metaproterenol; Physical Exertion; Prostaglandins; Terbutaline; Theophylline; Triamcinolone Acetonide

In a first chapter the author reviews the mechanisms of action of corticoids in respiratory diseases. Moreover the causes and the prevalence of unwanted side-effects are discussed. The advantages of synthetic glucocorticoids with short half-life time in pneumology are stressed. In the following chapters, the rationale of long-term corticoid treatments of asthma, in non allergic obstructive chronic lung diseases, in sarcoidosis and in the thoracic localisations of some collagen diseases is presented in detail. Regarding the treatment of asthma the author discusses the advantages of the alternate-day therapy, the use of corticoids in aerosols and the ratioale of ACTH. The usefulness of alternate-day therapy in sarcoidosis is also advocated.

Topics: Adrenocorticotropic Hormone; Aerosols; Asthma; Beclomethasone; Bronchitis; Chemical Phenomena; Chemistry; Chronic Disease; Collagen Diseases; Glucocorticoids; Humans; Lung Diseases, Obstructive; Respiratory Tract Diseases; Sarcoidosis; Time Factors

Topics: Asthma; Beclomethasone; Bronchi; Cromolyn Sodium; Glucocorticoids; Humans; Parasympatholytics; Sympathomimetics; Theophylline

Topics: Administration, Topical; Adrenal Cortex Hormones; Adrenal Glands; Adult; Asthma; Beclomethasone; Child; Cromolyn Sodium; Drug Therapy, Combination; Humans

Topics: Adrenocorticotropic Hormone; Adult; Asthma; Atropine; Beclomethasone; Child; Cromolyn Sodium; Epinephrine; Histamine; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Isoproterenol; Theophylline

Topics: Adrenal Glands; Adrenal Insufficiency; Aerosols; Asthma; Beclomethasone; Candidiasis, Oral; Child; Child, Preschool; Drug Evaluation; Growth; Humans; Hydrocortisone; Methylprednisolone

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aerosols; Asthma; Beclomethasone; Cromolyn Sodium; Humans; Isoproterenol; Respiratory Therapy; Triamcinolone Acetonide

Topics: Adolescent; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Carboxylic Acids; Child; Child, Preschool; Cromolyn Sodium; Cyclic AMP; Cyclic GMP; Humans; Hypertension, Pulmonary; Immunoglobulin E; Metaproterenol; Phenols; Prostaglandins; Pulmonary Atelectasis; Pulmonary Edema; Radiography; Respiratory Function Tests; Terbutaline; Tetrazoles; Xanthenes

Topics: Aerosols; Airway Obstruction; Anti-Bacterial Agents; Asthma; Bacteria; Bacterial Infections; Beclomethasone; Carbenicillin; Child; Clinical Trials as Topic; Colistin; Corticosterone; Dexamethasone; Gentamicins; Humans; Hydrocortisone; Kanamycin; Lung Diseases, Fungal; Placebos; Polymyxins; Respiratory Therapy; Triamcinolone Acetonide

Topics: Administration, Topical; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Glucocorticoids; Humans; Methylprednisolone; Prednisolone

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchiectasis; Cough; Double-Blind Method; Formoterol Fumarate; Humans

Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations.. In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 μg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed.. Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups.. Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Black or African American; Glucocorticoids; Hispanic or Latino; Humans; Quality of Life; Surveys and Questionnaires; Symptom Flare Up

A number of single-inhaler triple therapies are being developed for asthma, including the extrafine formulation of beclometasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium (G). Given asthma is a heterogenous disease, we investigated whether the clinical response to the addition of the long-acting muscarinic antagonist component within inhaled triple therapy was impacted by a range of clinical characteristics.. These were pre-specified and post-hoc sub-group analyses of TRIMARAN and TRIGGER, which were double-blind, 52-week studies comparing medium-strength (100/6/10 µg; TRIMARAN) and high-strength (200/6/10 µg; TRIGGER) BDP/FF/G with the respective BDP/FF strengths in adults with uncontrolled asthma and a history of ≥ 1 exacerbation. Co-primary endpoints were pre-dose forced expiratory volume in 1 s (FEV. Baseline clinical characteristics (pre-specified analyses) had no consistent effect on the lung function improvements with BDP/FF/G. For the exacerbation endpoints, sub-groups with higher reversibility gained greatest relative benefit from BDP/FF/G versus BDP/FF. In post-hoc analyses with patients sub-grouped by screening blood eosinophil values, in TRIMARAN the greatest relative effect of BDP/FF/G versus BDP/FF on the lung function endpoints was in the ≤ 300 cells/µL group; in TRIGGER, eosinophil levels did not markedly influence the relative efficacy of BDP/FF/G versus BDP/FF. Eosinophil levels did not influence relative efficacy on moderate-to-severe or severe exacerbations.. Overall, the relative efficacy of extrafine BDP/FF/G versus BDP/FF was not influenced by a range of clinical characteristics. However, some patient sub-groups gained additional benefit from BDP/FF/G for certain endpoints. In particular, for exacerbations the relative efficacy of BDP/FF/G was greater in more reversible patients. Trial registration ClinicalTrials.gov: TRIMARAN, NCT02676076 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676076?term=NCT02676076&draw=2&rank=1 ,); TRIGGER, NCT02676089 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676089?term=NCT02676089&draw=2&rank=1 ).

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Formoterol Fumarate; Glycopyrrolate; Humans; Male; Middle Aged; Muscarinic Antagonists; Treatment Outcome

Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett. Asthma Quality of Life Questionnaire (AQLQ) scores were collected in a previous study. TTO of improvements in Quality of Life was analysed for difference (TLA-placebo) in Area-under-Curve using backwards deletion from 12, 9, 6, 3 down to 1 month for the AQLQ total score, the four individual domains and specifically the sleep question.. Patients with uncontrolled asthma on GINA step 4 (n = 87)) reported a statistically significant and clinically relevant (≥0.5 point) improvement in total AQLQ score (0.57; p = 0.009) after 3 months treatment for TLA over placebo. The shortest TTO was within 1 month for the environmental domain (0.68; p = 0.016) and the sleep question (0.771; p = 0.037). TTO for the emotional and symptom domains was 3 months (0.66; p = 0.020 and 0.64; p = 0.014 respectively) and for the activity domain 6 months (0.47; p = 0.036).. Nocturnal avoidance of allergens using TLA provided a statistically significant and clinically relevant improvement in total AQLQ score within 3 months in patients in the GINA 4 + ACT<18 group. Questions related to sleep quality may provide the first signal of response already within a month after commencing treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Air Movements; Allergens; Asthma; Beclomethasone; Environment, Controlled; Exhalation; Female; Humans; Hypersensitivity; Inflammation; Male; Nitric Oxide; Quality of Life; Severity of Illness Index; Sleep; Temperature; Time Factors

The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients.. This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared.. The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Linear Models; Male; Middle Aged; Severity of Illness Index; Taiwan

Breath-actuated inhalers (BAI) eliminate the need for the hand-breath coordination required with standard metered-dose inhalers (MDI).. To evaluate the efficacy and safety of beclomethasone dipropionate (BDP) administered via BAI.. This 6-week, phase III, double-blind study included patients aged ≥12 years with persistent asthma. During the single-blind run-in, patients discontinued asthma medications and received twice-daily placebo BAI or MDI. At randomization, BAI patients received BDP BAI 320 μg/day, BDP BAI 640 μg/day, or placebo BAI, and MDI patients received BDP MDI 320 μg/day or placebo MDI. Assessments included standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from 0 to 6 weeks (AUEC[0-6 wk]) (obtained by clinic-based spirometry; the primary end point), morning peak expiratory flow (PEF), trough daily morning FEV1 (obtained by handheld spirometry), withdrawals, and tolerability.. Of 425 patients randomized, most were white (81%) and female (61%). BDP BAI 320 and 640 μg/day significantly improved FEV1 AUEC(0-6 wk) versus placebo (p < 0.001). The BDP BAI treatment groups exhibited significantly improved morning PEF and daily morning FEV1 versus placebo (p < 0.001). Similar treatment effects were demonstrated for BDP MDI (p < 0.001). Fewer patients withdrew due to worsening asthma while taking BDP BAI 320 μg/day (n = 1), BDP BAI 640 μg/day (n = 0), and BDP MDI 320 μg/day (n = 1) versus placebo (n = 10). BDP BAI was well tolerated.. BDP BAI demonstrated significant improvements in pulmonary function versus placebo, with results similar to BDP MDI. The safety profile of BDP BAI was comparable to BDP MDI, with no new safety signals.The study was registered on ClinicalTrials.gov (NCT02513160), www.clinicaltrials.gov.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Beclomethasone; Child; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Respiration; Respiratory Function Tests; Treatment Outcome; Young Adult

Holding chambers or spacers can enhance the efficacy of pressurized metered dose inhalers (pMDI) in delivering inhaled medications, as they reduce the need for hand-breath coordination and improve lower airways deposition. Nevertheless, their cost can be high for patients in low-income countries.. To compare asthma control achieved with beclomethasone-dipropionate administered through a hydrofluoroalkane-driven pMDI (BDp-pMDI) coupled to a home-made spacer (HmS) or to a valved commercial spacer (VCS) as auxiliary devices.. Sixty-three patients with poorly controlled asthma that had a BDp-pMDI prescription were randomized to use the inhaler coupled to a HmS made of 500 ml plastic bottles (Group HmS, n = 32) or to a VCS (Group VCS, n = 31) for 60 days. All were given training sessions. Asthma control was assessed through the Asthma Control Test (ACT) and forced expiratory volume in the first second (FEV1), both measured before, and 30 and 60 days after treatment began.. Both groups showed significant improvement in ACT scores after 30 and 60 days compared to baseline values (an increase of 7 and 7.8 points for the HmS group and 5.9 and 7.0 points for the VCS group, respectively, p < 0.001). There was no statistically significant difference in ACT scores between groups at any observation time (P = 0.261). FEV1 showed the same behavior.. A similar level of asthma control was achieved with beclomethasone-dipropionate administered through a pMDI whether the inhaler was coupled to the HmS or VCS. These results are significant for asthma control planning strategies in low-income communities. (Trial Register Number: RBR-5x4dc9).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Equipment Design; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome; Young Adult

Breath-actuated inhalers (BAI) eliminate the need for hand-breath coordination and, therefore, simplify the delivery of inhaled medication.. To evaluate the efficacy and safety of beclomethasone dipropionate BAI and metered-dose inhaler (MDI) versus placebo in pediatric patients ages 4-11 years with persistent asthma.. In this double-blind, double-dummy, phase III study, 628 children with persistent asthma were randomly assigned (1:1:1:1:1) to twice-daily beclomethasone dipropionate (BAI 80 μg/day, BAI 160 μg/day, MDI 80 μg/day, or MDI 160 μg/day) or to placebo. Efficacy over 12 weeks was assessed by spirometry, peak expiratory flow (PEF) measurements and other clinical end points. The primary efficacy end point was the baseline-adjusted trough morning percent predicted forced expiratory volume in 1 second (PPFEV1) area under the effect curve from 0 to 12 weeks (AUEC[0-12 weeks]).. PPFEV1 AUEC(0-12 weeks) showed numerical improvements from baseline in the BAI 80 μg/day and BAI 160 μg/day groups and MDI 80 μg/day and MDI 160 μg/day groups; however, these improvements were not significant versus placebo for any group after hierarchical testing was applied. Consistent improvements were noted in the active treatment groups versus placebo for the weekly average trough morning and evening PEFs, and with BAI 80 μg/day versus placebo for rescue albuterol/salbutamol use and the total daily asthma symptom score. Most patients indicated that the BAI device was easy or very easy to use. Adverse events were comparable across the groups; the incidence of oral candidiasis ranged from 0.8 to 3.2%.. Although the primary efficacy end point was not demonstrated, consistent improvements in PEF and other clinical end points were observed with beclomethasone dipropionate BAI, particularly at the 80 μg/day dose. These clinical benefits, combined with the need for better symptom control in children with asthma, supported the development of beclomethasone dipropionate BAI.

Topics: Age Factors; Asthma; Beclomethasone; Child; Child, Preschool; Female; Humans; Male; Metered Dose Inhalers; Nebulizers and Vaporizers; Respiratory Function Tests; Time Factors; Treatment Outcome

Breath-actuated inhalers (BAI) may simplify the delivery of inhaled medications compared with other devices.. To evaluate the efficacy and safety of beclomethasone dipropionate BAI versus matching placebo in adolescent and adult patients with persistent asthma.. This phase III, 12-week, double-blind study enrolled patients with asthma aged ≥12 years who were previously treated with a stable dose of inhaled corticosteroid or noncorticosteroid therapy. After a run-in period of 14 to 21 days, patients were randomly assigned in a 1:1:1 ratio to beclomethasone dipropionate BAI 80 or 160 micrograms/day (40 or 80 micrograms twice daily) or placebo BAI. The primary end point was the standardized baseline-adjusted trough morning forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 12 weeks (AUEC[0-12 weeks]). Secondary end points included peak expiratory flow, rescue medication use, asthma symptoms, and the time to withdrawal due to meeting predefined criteria for worsening asthma. Additional end points evaluated quality of life, instructions for use, and safety.. The full analysis and the safety sets included 270 and 273 patients, respectively. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had significant improvements in FEV1 AUEC(0-12 weeks) versus placebo (p ≤ 0.001). Improvements in secondary end points were also apparent in patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day compared with placebo. Patients who received beclomethasone dipropionate BAI 80 or 160 micrograms/day had greater increases in Asthma Quality of Life Questionnaire scores versus placebo patients at week 12. Of 98 patients who participated in the instructions-for-use substudy, 87 (88.8%) used the inhaler successfully on their first attempt. Treatment was generally safe and well tolerated.. Beclomethasone dipropionate BAI 80 and 160 micrograms/day were effective and well-accepted treatments in patients with asthma, with safety comparable to beclomethasone dipropionate delivered via a metered-dose inhaler.Clinical trial NCT02040779, www.clinicaltrials.gov.

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Young Adult

Smoking is as prevalent in asthmatics as in the general population. Asthmatic smokers benefit less from inhaled corticosteroids (ICS) than non-smoking asthmatics, possibly due to more smoking-induced small airways disease. Thus targeting small airways may be important in treating asthmatic (ex-)smokers. We hypothesized that extrafine particle ICS improve small airways function more than non-extrafine particle ICS in asthmatic (ex-)smokers.. We performed an open-label, randomized, three-way cross-over study comparing extrafine beclomethasone (HFA-QVAR) to non-extrafine beclomethasone (HFA-Clenil) and fluticasone (HFA-Flixotide) in 22 smokers and 21 ex-smokers with asthma (?5 packyears).. Similar effectiveness in improving small airways function was found for extrafine and non-extrafine particle ICS treatment for asthmatic smokers and ex-smokers.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adrenal Cortex Hormones; Adult; Airway Remodeling; Asthma; Beclomethasone; Bronchial Provocation Tests; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Particle Size; Respiratory Function Tests; Smokers; Treatment Outcome

Little is known of the long-term symptom profile in uncontrolled asthma and whether symptoms can predict distinct phenotypes. The primary objective of these analyses was to assess diurnal profile of cough and wheeze in an uncontrolled asthma population. Secondary outcomes were to examine how these symptom profiles influence response to treatment.Twice-daily electronically recorded data from 1701 patients were examined in relation to the population demographics. Reliever treatment with salbutamol was then compared with extra-fine beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation frequency was then correlated with the symptom profile.Symptoms were commoner in older patients with an increased body mass index. In most patients, reported cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and wheeze-predominant patients were identified; the former were overweight, older females and the latter older males. Diurnal symptoms of cough and wheeze were similarly attenuated by both therapies. MART reduced exacerbation frequency by a third compared with salbutamol, and this effect was greatest in patients with fewest reported symptoms.While cough and wheeze are highly correlated in uncontrolled asthma, some patients predominantly have cough whereas others wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting an alternative pathophysiology. MART may be the preferred option in those with fewest symptoms.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Age Distribution; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cough; Disease Progression; Female; Formoterol Fumarate; Humans; Incidence; Male; Middle Aged; Phenotype; Regression Analysis; Respiratory Sounds; Severity of Illness Index; United Kingdom

Pharmacodynamic assessment of the systemic effect of inhaled corticosteroids (ICSs) is often done by measuring 24-hour urine free cortisol (UFC) excretion. Knemometry assessing short-term lower-leg growth rate (LLGR) is a more rarely used alternative.. The primary aim of this study was to compare the sensitivity of LLGR and 24-hour UFC excretion for evaluating systemic exposure to ICSs in prepubertal children with asthma. The secondary aim was to evaluate factors influencing the precision of LLGR calculated by the traditional 1 leg nonparametric method versus a new 2 leg parametric method.. The study evaluated 60 children with mild asthma aged 5 to 12 years participating in a randomized controlled trial of ICSs with longitudinal concomitant assessments of LLGR and 24-hour UFC excretion. The sensitivity of the safety assessments was analyzed by comparing LLGR and 24-hour UFC in the placebo run-in period with values in the ICS treatment period by using paired t tests. Factors with a potential influence on LLGR were analyzed by means of ANOVA and the Levene test of homogeneity.. The mean LLGR was significantly reduced during the ICS versus placebo run-in periods: 0.18 mm/wk (SD, 0.55 mm/wk) versus 0.45 mm/wk (SD, 0.39 mm/wk), with a mean difference of 0.27 mm/wk (95% CI, 0.05-0.48 mm/wk; P = .02). In contrast, there was no difference in 24-hour UFC excretion: 6.91 nmol/mmol (SD, 4.67 nmol/mmol) versus 7.58 nmol/mmol (SD, 6.17 nmol/mmol), with a mean difference of 0.67 nmol/mmol (95% CI, -1.13 to 2.48 nmol/mmol; P = .46). We observed no significant difference in parametric determined LLGR caused by the child's age or sex, investigator, or season of measurement, whereas some differences were observed for the nonparametric LLGR.. These findings suggest that knemometry is a more sensitive pharmacodynamic measure of systemic effects of ICSs than 24-hour UFC excretion and that a parametric determination of LLGR increases the sensitivity of the method. These findings should be considered by legislative authorities in the future.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child Development; Child, Preschool; Female; Humans; Hydrocortisone; Leg; Male

Breath-actuated inhalers (BAI) have been developed to simplify the delivery of inhaled medication.. To evaluate the safety and efficacy of beclomethasone dipropionate hydrofluoroalkane BAI and metered-dose inhaler (MDI) versus placebo in patients who previously used a mid- to high-dose inhaled corticosteroid or inhaled corticosteroid/long-acting beta agonist for persistent asthma.. This phase III study included five treatment groups: placebo, and four beclomethasone dipropionate groups (BAI 320 μg/day, BAI 640 μg/day, MDI 320 μg/day, and MDI 640 μg/day). Efficacy over 12 weeks was assessed by spirometry, peak flow measurements, and other clinical end points. Safety was assessed by adverse events.. Baseline-adjusted trough morning forced expiratory volume in 1 second area under the effect curve from time 0 to 12 weeks (primary end point) was increased in the BAI 320 and BAI 640 μg/day groups and the MDI 640 μg/day group versus placebo (not significant). Clinically important improvements were noted in morning and evening peak expiratory flow and decreased rescue medications. More patients who received placebo than patients in active treatment groups withdrew due to meeting the stopping criteria for worsening asthma. Patients in the active treatment groups experienced a greater decrease in asthma symptoms than patients in the placebo group. Quality of life and Asthma Control Test scores improved in the active treatment groups compared with the placebo group (p ≤ 0.0074). The most common adverse events (>5% in any group) were oral candidiasis and upper respiratory tract infection.. Clinical benefits for patients who used BAI 320 and 640 μg/day and MDI 640 μg/day were demonstrated. The safety profiles of BAI 320 and 640 μg/day were comparable with that of the MDI. These benefits and the continued need for better symptom control among patients with asthma support the continued development of this controller medication. ClinicalTrials.gov identifier NCT02031640.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Female; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Retreatment; Risk Factors; Time Factors; Treatment Outcome; Young Adult

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

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

A high strength of beclomethasone/formoterol fumarate (BDP/FF) in a pressurised metered dose inhaler (pMDI), which contains extrafine BDP (200 μg/actuation) and FF (6 μg/actuation) has been developed to treat those asthmatics who are not adequately controlled on previous treatments.. A 12-week, randomized, double-blind, parallel group study was performed to compare the efficacy and safety of pMDI BDP/FF 200/6 (two actuations bid) with BDP 100 μg (four actuation bid) in a population of 376 randomized adult asthmatics not adequately controlled with high dose of inhaled corticosteroids (ICS) or medium dose of ICS plus long acting β. The primary endpoint [change from baseline over the entire treatment period in average pre-dose morning peak expiratory flow (PEF)] demonstrated the superiority of BDP/FF over BDP monotherapy, with an adjusted mean difference of 19 L/min, which is above the minimal important clinical difference reported for this parameter. Overall, BDP/FF and BDP showed a similar improvement of symptom-based parameters and of the use of rescue medication after 3-month treatment. The safety profile of the two drugs was comparable, although BDP monotherapy, but not BDP/FF, slightly reduced the levels of serum cortisol.. The study proved that pMDI BDP/FF 200/6 μg was superior to BDP alone in improving lung function with comparable safety profiles. Therefore it may be considered as an effective treatment for adults with asthma not adequately controlled with high dose of ICS monotherapy or medium dose of ICS/LABA combinations.. ClinicalTrials.gov: NCT01577082 , date 06/04/2012.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Italy; Male; Metered Dose Inhalers; Middle Aged; Patient Safety; Severity of Illness Index; Treatment Outcome; Young Adult

Asthma guidelines recommend prescription of inhaled corticosteroids at a reduced dosage in children compared to older patients in order to minimize the systemic exposure and risk of unwanted side effects. In children, pressurized metered dose inhalers (pMDI) are recommended in combination with a valved holding chamber (VHC) to overcome the problem of coordinating inhalation with actuation. However, the influence of age and body size on the systemic exposure of drugs to be administered via a pMDI with VHC is still not fully elucidated. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed combination of beclometasone-dipropionate/formoterol-fumarate administered via pMDI with VHC in children, adolescents and adults.. The pharmacokinetics of formoterol and beclometasone-17-monopropionate (active metabolite of beclometasone-dipropionate) was evaluated over 8 h from three studies, each performed in a different age and body size group. Children (7-11 years, n = 20), adolescents (12-17 years, n = 29) and adults (≥18 years, n = 24) received a single dose of beclometasone/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via pMDI with AeroChamber Plus™.. The systemic exposure in children in comparison to adolescents was equivalent for formoterol while it was halved for beclometasone-17-monopropionate in accordance with the halved dose of beclometasone administered in children (90% CIs within 0.8-1.25 for formoterol and 0.4-0.625 for beclometasone-17-monopropionate). The systemic exposure to beclometasone-17-monopropionate and formoterol was equivalent between adolescents and adults.. The systemic exposure to the active ingredients of a fixed dose combination of beclometasone/formoterol administered via pMDI with AeroChamber Plus™ correlates with the nominal dose independently of patient age and body size. Thus, dose reduction in relation to age when using a pMDI with VHC may be unnecessary for reducing the systemic exposure in children.

Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Young Adult

Suppression of small airway inflammation may contribute to achieving asthma control. We aimed to evaluate the additional effect of beclometasone dipropionate/formoterol (BDP/F) hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) (BDP/F-HFA 100/6 μg pMDI) on airway inflammation and functional parameters in asthma cases, who were optimally controlled by maintenance therapy.. Ninety-five controlled asthmatic patients were included. They were grouped as Group 1 [budesonide/formoterol 320/9 μg dry powder inhaler (DPI)] and Group 2 (fluticasone/salmeterol 500/50 μg DPI) according to the combination they used. Then Group 3 was established by random selection from these two groups, and BDP/F-HFA 100/6 μg pMDI treatment was prescribed. All patients were evaluated in the beginning of the study and were re-evaluated at the end of a 3-week treatment period by spirometry, exhaled nitric oxide (eNO) levels, and small airway functional indices, namely, Sacin and Scond values.. There was no significant statistical difference in terms of age, height, weight, disease duration, symptoms, and spirometric parameters between the groups. There was a significant decrease in eNO levels in asthma cases who were on BDP/F-HFA therapy (p=0.001). A significant improvement in Sacin values at the end of the treatment period was observed in cases treated with BDP/F-HFA (p=0.001), indicating that inflammation was suppressed in peripheral airways.. These results emphasize that asthma treatment has mainly focused on the strategy to keep the disease under control; maintaining optimal functional level might be underestimated. BDP/F-HFA may have an additional favorable effect on the peripheral airway inflammation in the controlled asthma.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Breath Tests; Bronchodilator Agents; Drug Combinations; Dry Powder Inhalers; Female; Formoterol Fumarate; Glucocorticoids; Humans; Lung; Male; Middle Aged; Particle Size; Powders; Recovery of Function; Spirometry; Time Factors; Treatment Outcome

The fixed combination of extrafine beclomethasone dipropionate and formoterol fumarate (BDP/FF) pMDI (Foster(®)) is approved for treatment of adult asthmatic patients. In order to provide an alternative drug delivery system for BDP/FF to physicians and patients, a dry powder inhaler (NEXThaler(®)) has been developed, capable to deliver extrafine particles to the lungs and therefore improve the dosing of the drugs, especially in patients with poor hand-breath coordination.. This trial was performed to compare efficacy and safety of extrafine BDP/FF NEXThaler(®) with extrafine BDP/FF pMDI or non-extrafine BDP DPI alone in adult patients with controlled asthma.. In this 8-week randomised, double-blind, parallel-group trial, patients were randomized to receive either extrafine BDP/FF NEXThaler(®) 100/6 μg bid, extrafine BDP/FF 100/6 μg pMDI bid or non-extrafine BDP DPI 100 μg bid. The primary efficacy variable was change from baseline to the entire 8-week randomised treatment period in average pre-dose morning PEF.. The ITT population comprised 754 patients. Extrafine BDP/FF NEXThaler(®) was non-inferior (pre-defined margin: -15 L/min) relative to extrafine BDP/FF pMDI (mean difference: -1.84; 95% CI: -6.73, 3.05) in terms of the primary efficacy variable, change from baseline in average pre-dose morning PEF. Statistical superiority of both extrafine BDP/FF formulations over non-extrafine BDP DPI was demonstrated for the primary efficacy variable (providing evidence of assays sensitivity of the trial), ACQ score and percentage of rescue medication use-free days. No significant safety signals were observed.. NEXThaler(®) is an effective and well-tolerated delivery device for treatment of patients with asthma who need a regular treatment.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Dry Powder Inhalers; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Treatment Outcome; Young Adult

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

Statins have pleiotropic immunomodulatory effects that may be beneficial in the treatment of asthma. We previously reported that treatment with atorvastatin improved asthma symptoms in smokers with asthma in the absence of a change in the concentration of a selection of sputum inflammatory mediators.. To determine the effects of atorvastatin alone and in combination with inhaled corticosteroid on a range of sputum cytokines, chemokines and growth factors implicated in the pathogenesis of asthma, and their association with asthma control questionnaire (ACQ) and/or asthma quality of life questionnaire (AQLQ) scores.. Sputum samples were analysed from a sub-group of 39 smokers with mild to moderate asthma recruited to a randomised controlled trial comparing atorvastatin (40 mg/day) versus placebo for four weeks, followed by inhaled beclometasone (400 μg/day) for a further four weeks. Induced sputum supernatant fluid was analysed (Luminex or biochemical analyses) for concentrations of 35 mediators.. Sputum mediator concentrations were not reduced by inhaled beclometasone alone. Atorvastatin significantly reduced sputum concentrations of CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-α and MMP-8 compared with placebo and, when combined with inhaled beclometasone, reduced sputum concentrations of MMP-8, IL-1β, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G-CSF and CCL7 compared to ICS alone. Improvements in ACQ and/or AQLQ scores with atorvastatin and ICS were associated with decreases in G-CSF, IL-7, CCL2 and CXCL8.. Short-term treatment with atorvastatin alone or in combination with inhaled beclometasone reduces several sputum cytokines, chemokines and growth factors concentrations unresponsive to inhaled corticosteroids alone, in smokers with asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Atorvastatin; Beclomethasone; Chemokines; Cytokines; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Male; Middle Aged; Quality of Life; Severity of Illness Index; Sputum

The aim was to investigate the pharmacokinetics and pharmacodynamics of an extrafine pressurized metered-dose inhaler (pMDI) fixed combination of beclometasone dipropionate (BDP)/formoterol fumarate (FF) in adolescent and adult asthma.. This was a three-way crossover study, on 30 asthmatic adolescents receiving BDP/FF pMDI with or without a valved holding chamber (VHC) or a free licenced combination of BDP pMDI and FF pMDI plus a parallel arm of 30 asthmatic adults receiving BDP/FF pMDI. All patients received a single dose of BDP and FF of 400 µg and 24 µg, for each treatment, respectively. Assessments were performed over 8 hours.. In adolescents, the 90% confidence intervals (CIs) for the systemic exposure (AUC(0,t)) geometric mean ratio of the fixed combination with or without VHC vs. the free combination were within the bioequivalence range 0.80-1.25, both for beclometasone-17-monopropionate (B17MP, the active metabolite of BDP) and formoterol. Pharmacodynamic variables for plasma potassium and glucose, pulse rate and pulmonary function in adolescents were equivalent between treatments, 95% CI within 0.9, 1.09. The upper level of 90% CIs for AUC(0,t) geometric mean ratio adolescents : adults of B17MP and formoterol after treatment with BDP/FF pMDI was lower than 1.25, 90% CI 0.78, 1.04 and 0.86, 1.17, respectively.. In adolescents the pharmacodynamics and the overall systemic exposure to the active ingredients of an extrafine fixed combination of BDP/FF pMDI with or without a VHC was equivalent to that of a free licenced combination of pMDIs of established safety and efficacy profiles. The systemic exposure in adolescents was not higher than in adults. These results support the indication for use of inhaled corticosteroid/long acting β2 -adrenoceptor agonist pMDIs in adolescents at the same dosage as in adults.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Area Under Curve; Asthma; Beclomethasone; Cross-Over Studies; Drug Combinations; Formoterol Fumarate; Humans; Metered Dose Inhalers; Treatment Outcome

Inhaled corticosteroids (ICS) treatment for asthma control is generally focused on lung function and symptoms, but inadequately correlated with airway inflammation.. To compare asthma control in a group of patients whose treatment was based on fraction of exhaled nitric oxide (FENO) and sputum eosinophils (intervention group) with a group in whom treatment was based on clinical score (control group). Study design and primary outcome: Randomized parallel-group longitudinal 24-month study including 5 visits every 6 months. A combination of asthma exacerbation rate and symptom score at 24 months was the primary outcome.. Fourteen patients with eosinophilic asthma per group were included.. In the intervention group, exacerbation rate/patient/year was reduced at 12 months (0.82) (-73%) and, to a greater extent at 24 months (0.5) (-84%) compared with baseline (3.21, p<0.01). In the control group, a significant reduction in exacerbation rate/patient/year was only observed between month 12 (3.0) and 24 (2.0, -33%, p<0.01). At 24 months, exacerbation rate was lower (-75%) in the intervention (0.5) than in the control group (2.0, p<0.05). Compared with baseline, mean symptom scores at 24 months were reduced in both groups (intervention group: -72%; control group: - 60%), but were lower in the intervention (8.1±1.0, p<0.05; -27%) than in the control group (11±2.6). ICS dose gradually increased in both groups throughout the study, with no between-group differences.. Compared with conventional strategy, longitudinal monitoring of FENO and sputum eosinophils improves eosinophilic asthma control in terms of reduced symptoms and exacerbations without additional increase e in ICS treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Beclomethasone; Cohort Studies; Eosinophils; Exhalation; Female; Humans; Leukocyte Count; Longitudinal Studies; Male; Monitoring, Physiologic; Nitric Oxide; Prospective Studies; Respiratory Function Tests; Single-Blind Method; Sputum; Treatment Outcome

Inhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS) offers acute, but moderate protection against exercise induced bronchoconstriction (EIB). This study investigated whether inhaling a single dose of ICS in a forward leaning posture improves this protection against EIB.. 32 Asthmatic children, 5-16 years, with EIB (Median fall in FEV1 or FEV0.5 30.9%) performed two exercise challenge tests (ECT's) with spirometry in a single blinded cross-over trial design. Children inhaled a single dose of 200 μg beclomethasone dipropionate (BDP) 4 h before the ECT, once in the standard posture and once with the neck extended in a forward leaning posture. Spirometry was also performed before the inhalation of the single dose of BDP.. Inhalation of BDP in both body postures provided similar protection against EIB (fall in FEV1 or FEV0.1 in standard posture 16.7%; in forward leaning posture 15.1%, p = 0.83). Inhaling ICS in a forward leaning posture significantly delayed EIB compared to inhaling in the standard posture (respectively 2.5 min ± 1.0 min vs. 1.6 min ± 0.8 min; difference 0.9 min (95CI 0.25; 1.44 min); p = 0.01).. Inhalation of a single dose BDP in both the forward leaning posture and the standard posture provided effective and similar protection against EIB in asthmatic children, but the forward leaning posture resulted in a delay of EIB.. NTR3432 (www.trialregister.nl).

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Beclomethasone; Bronchoconstriction; Child; Child, Preschool; Cross-Over Studies; Exercise Test; Female; Forced Expiratory Volume; Heart Rate; Humans; Male; Posture; Respiratory Function Tests; Spirometry

Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is unclear.. We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma.. The studies of 6-12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3802 patients, aged 12-70 years who received either roflumilast 100 μg, 250 μg or 500 μg once daily, BDP 400 μg or 500 μg twice daily, or 10 mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV1) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication.. Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV1. Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure.. Roflumilast improves FEV1 and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.

Topics: Acetates; Adolescent; Adult; Aged; Aminopyridines; Asthma; Beclomethasone; Benzamides; Child; Cyclopropanes; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Phosphodiesterase 4 Inhibitors; Quinolines; Sulfides; Young Adult

The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma.. To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005.. The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4 to 24 weeks. Data were analyzed from 4873 patients, 12-70 years of age, of whom 2668 received roflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500 μg versus placebo. In two studies, 500 μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250 μg fluticasone propionate, or 400 μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation.. Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500 μg roflumilast/400 μg BDP versus placebo/400 μg BDP.. Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.

Topics: Adolescent; Adult; Aged; Aminopyridines; Asthma; Beclomethasone; Benzamides; Child; Cyclopropanes; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Phosphodiesterase 4 Inhibitors; Quality of Life; Young Adult

Previously, we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6.. This is a 6-year follow-up report of a randomized placebo-controlled trial, in which 185 infants hospitalized for respiratory syncytial virus bronchiolitis were treated with early initiated, high-dose inhaled beclomethasone (n = 86) or placebo (n = 99) for 3 months. The primary outcome was forced expiratory volume in 1 second as percentage predicted. Secondary outcomes were bronchial hyperresponsiveness, physician-diagnosed asthma, hay fever and eczema. Possible toxicity was assessed by linear growth measurements.. At age 6, no significant differences were found in mean forced expiratory volume in 1 second percentage predicted between beclomethasone-treated and placebo-treated patients (91.4 vs. 93.4, mean difference 2.05 (95% confidence interval: -1.98 to 6.08). The proportion of bronchial hyperresponsiveness, physician-diagnosed asthma, parent reported hay fever and eczema was comparable between groups. There were no differences in linear growth.. Early initiated prolonged treatment with high-dose inhaled beclomethasone during hospitalization for respiratory syncytial virus infection during infancy did not improve the long-term respiratory outcome, but was safe.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchiolitis; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Respiratory Syncytial Virus Infections

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biological Availability; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Dry Powder Inhalers; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Patient Compliance

The murine asthma model shows that switching off airway β2 receptors with an inverse agonist may confer anti-inflammatory effects as well as corticosteroid-sparing activity. We have assessed for any corticosteroid-sparing effects of propranolol, an inverse agonist, added to low-dose inhaled corticosteroid (ICS) compared with higher dose ICS. A randomized double-blind placebo-controlled cross-over trial in mild-to-moderate persistent asthmatic patients was performed. After a run-in (2 weeks) on hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) at 100 μg/day (HFA-BDP100), patients received randomized treatments (4 weeks) with propranolol at 80 mg/day plus HFA-BDP at 100 μg/day compared with placebo plus HFA-BDP at 400 μg/day (HFA-BDP400). Propranolol was up-titrated to 80 mg/day over the initial 2 weeks. Tiotropium was co-administered until 5 days before each histamine challenge (the primary outcome). Sixteen patients completed the study [mean age, 38 years; forced expiratory volume in 1 s (FEV1), 86.4%; histamine provocative concentration causing a 20% fall in FEV1 (PC20), 1.39 mg/ml; ICS dose, 406 μg/day]. Histamine PC20 was unchanged by adding propranolol to HFA-BDP100 compared with baseline (HFA-BDP100) {0.17 doubling dilution (dd) difference [95% confidence interval (CI): -0.58 to 0.92]}, but there was a significant improvement with HFA-BDP400 compared with both baseline [1.05 dd (95% CI: 0.43-1.66); P=0.02], and propranolol+HFA-BDP100 [0.88 dd (95% CI: 0.45-1.30); P=0.006]. Significant improvements were also observed with HFA-BDP400 for exhaled nitric oxide, blood eosinophils, serum eosinophilic cationic protein and asthma quality-of-life questionnaire symptoms compared with propranolol+HFA-BDP100. Salbutamol recovery post-challenge was partially blunted by propranolol (median prolongation 5 min; P=0.002). Domiciliary evening FEV1 also fell with propranolol+HFA-BDP100 [mean reduction from baseline 0.22 litres (95% CI: 0.10-0.34); P=0.012], whereas Asthma Control Questionnaire remained unchanged. In conclusion, the inverse agonist propranolol produced no improvements when given with low-dose ICS, whereas further significant improvements in airway hyper-responsiveness and inflammation were demonstrated with higher dose ICS. Thus, propranolol does not confer corticosteroid-sparing activity in persistent asthma.

Topics: Adult; Asthma; Beclomethasone; Bronchial Provocation Tests; Creatinine; DNA-Binding Proteins; Double-Blind Method; Eosinophilia; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Nuclear Proteins; Potassium; Propranolol; Transcription Factors

Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults.. The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via DPI.. The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001).. The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.

Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Aged; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Size; Child; Cross-Over Studies; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Half-Life; Humans; Metered Dose Inhalers; Middle Aged; Young Adult

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

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

Asthma management focuses on achieving and maintaining asthma control. Few studies have assessed whether complete and sustained asthma control is maintained in clinical practice after stepping-across ICS/LABA fixed combinations. Aim of this double-blind, double-dummy, randomized, parallel group, controlled study was to demonstrate clinical equivalence between equipotent doses of extrafine beclometasone/formoterol (BDP/F) pMDI and fluticasone/salmeterol (FP/S) Diskus® in maintaining lung function and asthma control.. A total of 416 asthmatic patients already controlled with FP/S 500/100 μg/day (Diskus®, pMDI or separate inhalers) were randomized to a 12-week treatment with extrafine BDP/F 400/24 μg/day pMDI or FP/S 500/100 μg/day Diskus®. Pre-dose 1-s forced expiratory volume (FEV(1)) was the primary efficacy variable; secondary variables included asthma control questionnaire (ACQ-7) and FEV(1)0-1 h area under the curve (FEV(1)AUC(0-1h)). Safety was assessed through adverse events monitoring and vital signs.. After 12 weeks of treatment, pre-dose FEV(1) did not differ between treatments (difference between means 0.01 L; 95% CI -0.03-0.06 L) with no significant changes from baseline in both groups (p = 0.726 and p = 0.783 in BDF/F arm and FP/S, respectively). ACQ-7 score showed that control was maintained after stepping-across to extrafine BDP/F. FEV(1)AUC(0-1h) was significantly higher in BDP/F arm at the beginning (p = 0.004) and at the end of the 12-week treatment period (p = 0.019). No safety issues were reported in both groups.. Patients previously controlled with FP/S in any device formulation can effectively step-across to extrafine BDP/F pMDI, maintaining lung function and asthma control with a 5-min onset of action.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Particle Size; Respiratory Function Tests; Time Factors; Treatment Outcome

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

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

GINA guideline recommends stepping down treatment of asthma patients where control is achieved. The aim of this analysis was to estimate the costs and health outcomes associated with step down of controlled patients on high dose fluticasone/salmeterol (FP/S 1000/100 μg daily) to either medium dose FP/S (500/100 μg) dry powder or extrafine beclometasone/formoterol (BDP/F 400/24 μg) pMDI in three European countries.. A patient-level simulation Markov model was constructed to enable the simulation of three comparative arms (FP/S 1000/100, FP/S 500/100, BDP/F 400/24). Transition probabilities and healthcare resources consumption were derived from a multinational clinical trial comparing BDP/F 400/24 μg vs. FP/S 500/100 μg as step down therapy in asthma. Direct costs and health state utilities were sourced from public source and published literature. The analysis was conducted from a health system perspective, based on six months horizon. Probabilistic sensitivity analyses were conducted.. The ICER (Incremental Cost-Effectiveness Ratio) associated with high dose dry powder FP/S 1000/100 μg vs. extrafine BDP/F 400/24 μg was above 70,000 GBP and 200,000 €/QALY (Quality Adjusted Life Years). An ICER of 29,000 GBP/QALY and above 30,000 €/QALY was associated with medium dose dry powder FP/S 500/100 μg vs. BDP/F 400/24 μg.. It was found that maintaining controlled patients on high dose FP/S is not cost-effective. Extrafine BDP/F 400/24 μg daily can be considered to be a cost-effective option in the countries analyzed to maintain control of asthmatic patients stepped down from high dose FP/S 1000/100 μg daily dry powder or suspension formulations.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Costs; Ethanolamines; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Health Care Costs; Humans; Markov Chains; Models, Econometric; Netherlands; Quality-Adjusted Life Years; Spain; United Kingdom

According to international treatment guidelines, inhaled rapid-acting β2 agonists should be used for the control of symptoms in patients with asthma. We compared the efficacy and safety of an extrafine combination inhaler containing a corticosteroid (beclometasone) plus a rapid-onset, long-acting β2 agonist (formoterol) with a short-acting β2 agonist (salbutamol) as reliever strategies in patients taking beclometasone-formoterol combination as maintenance treatment.. In a double-blind trial undertaken in 183 centres in 14 European countries over 48 weeks, patients (aged ≥18 years) with asthma that was not fully controlled, with a forced expiratory volume in 1 s (FEV1) of at least 60% predicted, had a 2-week run in. During this period, patients were treated with a combination of beclometasone 100 μg and formoterol 6 μg per one inhalation twice daily plus salbutamol 100 μg as required delivered by use of a pressurised metered-dose inhaler. They were then randomly assigned in a 1:1 ratio with a computer-generated randomisation list to receive beclometasone 100 μg plus formoterol 6 μg or salbutamol 100 μg as reliever in addition to maintenance with beclometasone 100 μg plus formoterol 6 μg twice daily. Primary outcome was the time to first severe exacerbation (admission to hospital or visit to emergency department, or use of systemic steroids for ≥3 consecutive days). Secondary outcomes were number of severe exacerbations (events per 100 patients per year), time to and number of mild exacerbations, additional exacerbation variables, lung function, symptom scores, and asthma control. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00861926.. 1714 patients were randomly assigned to the as-needed beclometasone-formoterol (n=857) and as-needed salbutamol groups (n=857), and 1701 were analysed (852 and 849, respectively). 326 severe exacerbations were reported by 251 patients during the study, and 99 versus 152 patients had at least one exacerbation during the 48 weeks, respectively. Compared with beclometasone-formoterol plus salbutamol as needed, beclometasone-formoterol for both maintenance and reliever treatment significantly increased the time to first exacerbation (209 days vs 134 days) by 75 days, with a 36% reduction in risk (hazard ratio 0·64 [95% CI 0·49 to 0·82]; p=0·0005), and the estimated probability was 12% and 18%, respectively (p=0·0003). The number of days with mild asthma exacerbations was also lower with as-needed beclometasone-formoterol than with as-needed salbutamol (56·04 days per patient per year vs 65·11 days per patient per year; 0·86 [0·76 to 0·98]; p=0·021). From the run-in period to week 48, both treatments improved symptoms (mean change -1·59 [-1·94 to -1·25] in the as-needed beclometasone-formoterol group vs -1·44 [-1·78 to -1·10] in the as-needed salbutamol group, difference -0·15 [-0·60 to 0·30]; p=0·507), percentage of asthma control days (9·5% [7·3 to 11·8] vs 10·9% [8·7 to 13·1], respectively, -1·4 [-4·3 to 1·6]; p=0·359), use of reliever (-0·29 [-0·38 to -0·20] vs -0·27 [-0·36 to -0·19], respectively, -0·02 [-0·13 to 0·10]; p=0·794), and lung function (FEV1, 0·090 [0·060 to 0·120] vs 0·090 [0·060-0·120], respectively, 0·001 [-0·040 to 0·040]; p=0·969), and were well tolerated (patients with serious adverse events, 32 [4%] and 41 [5%], respectively).. Our results lend support to the use of the combination of a single inhaled corticosteroid plus a rapid-onset, long-acting β2 agonist for maintenance and relief in patients with moderate to severe asthma and provide encouraging data for the formulation of beclometasone-formoterol for this use.. Chiesi Farmaceutici.

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

The fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 μg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 μg vs. the free combination of BDP and formoterol pMDIs in asthmatic children.. Children aged 5-11 years old inhaled BDP 200 μg and formoterol 24 μg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,∞), AUC(0,0.5 h, Cmax , tmax , t1/2 ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored.. Twenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml(-1)  h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml(-1)  h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related.. BDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biological Availability; Child; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucose; Heart Rate; Humans; Hydrocortisone; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate; Potassium

We aimed to evaluate the therapeutic effect of nebulized beclomethasone dipropionate (nBDP) on both allergic asthma and rhinitis. In a randomized, double-blind, placebo-controlled study, 40 children (mean age 10.7 ± 2.1 years) with allergic asthma and rhinitis received either nBDP (daily dose of 800 µg, administered twice daily) or placebo for 4 weeks (with a face mask), after a 2-week run-in period of clinical assessment. Nasal and oral fractional exhaled nitric oxide (FeNO) measurements together with pulmonary function tests, nasal and oral exhaled breath condensate (EBC) collection for pH and interleukin-5 (IL-5) measurements as well as nasal and bronchial symptom scores were obtained at baseline and after 4-week treatment. A significant improvement in oral FeNO, oral and nasal EBC IL-5 and nasal EBC pH was observed in the nBDP group when comparing the values with baseline, together with an improvement in symptom score of the visual analogue scale, nasal obstruction, sneezing, rhinorrhea, breathing difficulty, cough, wheezing and sleep disturbance (nBDP end treatment vs. baseline, Wilcoxon signed-rank test). nBDP was more effective than placebo (ANCOVA test) in improving [difference Δ = response after treatment at the last visit (active or placebo) - value at baseline] nasal pH, oral IL-5, oral FeNO, forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, peek expiratory flow, visual analogue scale, breathing difficulty, cough, wheezing and sleep disturbance scores. No differences were observed between the nBDP and the placebo group for symptom score of rhinitis. nBDP is a useful treatment for airway inflammation and clinical status in children with concomitant allergic asthma and rhinitis.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Beclomethasone; Breath Tests; Child; Double-Blind Method; Female; Humans; Immunoglobulin E; Interleukin-5; Male; Nebulizers and Vaporizers; Nitric Oxide; Pilot Projects; Respiratory Function Tests; Rhinitis, Allergic, Perennial

Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response.. We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma.. In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734).. All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled" (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration.. Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Immunoglobulin E; Male; Middle Aged; Nitric Oxide; Oligonucleotides; Toll-Like Receptor 9; Young Adult

To which extent volume spacers may influence systemic activity of inhaled beclomethasone dipropionate (BDP) has not been evaluated.. To assess whether the AeroChamber Plus™ spacer is equivalent to the Volumatic™ spacer for administration of inhaled hydroflouroalkane 134a propelled BDP in terms of lower leg growth rate (LLGR).. Prepubertal children with mild asthma (n = 26, aged 6-14 years) were included in a 3-time periods of 2 weeks duration randomized double-blind cross-over study with a single-blind placebo run-in and two washout periods. LLGR was measured with the knemometer. Interventions were inhaled BDP hydroflouroalkane 134a pressurized metered dose inhaler 100 μg and 200 μg b.i.d. with the AeroChamber Plus and 200 μg b.i.d. with the Volumatic spacer.. Beclomethasone dipropionate 200 μg b.i.d. from the AeroChamber Plus was non-inferior to BDP 200 b.i.d. from the Volumatic spacer as the lower margin of confidence interval of the difference between treatments (-0.18 to 0.13 mm/week) was greater than the prespecified lower limit for non-inferiority (-0.20 mm/week). UFC/creatinine data showed no statistically significant variations.. The systemic activity of BDP, via the Volumatic™, and AeroChamber Plus™ spacers is similar. The AeroChamber Plus spacer may be used in children without risk of increasing systemic activity of BDP.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Cross-Over Studies; Double-Blind Method; Female; Humans; Leg; Male; Nebulizers and Vaporizers; Treatment Outcome

The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown.. We sought to determine the association between ventilation heterogeneity and current asthma control before and after ICS treatment.. Adult subjects with asthma had lung function and asthma control (5-item Asthma Control Questionnaire [ACQ-5 score] ≥1.5 = poorly controlled, ACQ-5 score ≤0.75 = well controlled) measured at baseline. A subgroup with AHR had repeat measurements after 3 months of high-dose ICS treatment. The indices of ventilation heterogeneity in the regions of the lung where gas transport occurs predominantly through convection (ventilation heterogeneity in convection-dependent airways [Scond]) and through diffusion (ventilation heterogeneity in diffusion-dependent airways [Sacin]) were derived by using the multiple-breath nitrogen washout technique.. At baseline (n = 105), subjects with poorly controlled asthma had worse FEV(1), fraction of exhaled nitric oxide measured at 200 mL/s (Feno), Scond, and Sacin values. In the treatment group (n = 50) spirometric, Feno, residual volume (RV)/total lung capacity (TLC), AHR, and Scond values significantly improved. Asthma control also improved (mean ACQ-5 score, 1.3-0.7; P < .0001). The change in ACQ-5 score correlated with changes in Feno (r(s) = 0.31, P = .03), Sacin (r(s) = 0.32, P = .02), and Scond (r(s) = 0.41, P = .003) values. The independent predictors of a change in asthma control were changes in Scond and Sacin values (model r(2) = 0.20, P = .005).. Current asthma control is associated with markers of small-airways disease. Improvements in ventilation heterogeneity with anti-inflammatory therapy are associated with improvements in symptoms. Sensitive measures of small-airway function might be useful in monitoring the response to therapy in asthmatic subjects.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Humans; Male; Nitric Oxide; Plethysmography; Skin Tests; Spirometry

There are only a few studies assessing the relationship between adherence rate to ICS, as assessed by electronic monitoring, and the level of asthma control in childhood. The present study was carried out to examine the relationship between adherence to beclomethasone diproprionate (BDP) as well as other factors related to poor asthma control. In this prospective cohort study, 102 steroid naïve randomly selected subjects with persistent asthma, aged 5-14 years were prescribed 500-750 μg daily of BDP-CFC and followed during one year. Adherence to BDP was measured electronically in the 4th, 8th and 12th months of study. The level of asthma control was classified as either controlled or uncontrolled instead of the current three categories recommended by the Global Initiative for Asthma (GINA). Mean adherence rate was higher in patients with controlled asthma during follow-up, but went down from 60.4% in the 4th month to 49.8% in the 12th month (p = 0.038). Conversely, among patients with uncontrolled asthma, the mean adherence rate decreased from 43.8% to 31.2% (p = 0.001). Multivariate analysis showed that the level of asthma control was independently associated to the adherence rate in all follow-up visits (p-values equal or lower than 0.005). The level of asthma control was directly proportional to adherence rate. Our results suggest that a BDP daily dose by 300 μg seems to be enough to attain control over mild and moderate persistent asthma, including exercise induced asthma.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Child; Child, Preschool; Drug Administration Schedule; Drug Monitoring; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Prospective Studies; Socioeconomic Factors; Treatment Outcome

The efficacy and safety of extrafine beclomethasone dipropionate 100 μg/formoterol 6 μg (BDP/F HFA) pressurized metered dose inhaler (pMDI) in patients with moderate-to-severe persistent asthma, has been demonstrated in randomised controlled trials (RCTs). The aim of this prospective observational study was to assess real-life effectiveness in terms of asthma control in smoking (most of the time excluded from RCTs) and non-smoking asthmatics.. Adult patients with persistent asthma, in whom treatment with an inhaled corticosteroid/long-acting β(2)-agonist (ICS/LABA) combination is indicated, were included. Pulmonary function (FEV1%pred or PEF absolute value), Asthma Control Questionnaire (ACQ) and asthma control according to GINA criteria were measured at baseline as well as 2-8 months and >8-14 months after treatment initiation with BDP/F HFA.. Overall, 619 patients were enrolled by 97 investigators. In the effectiveness cohort (N = 568), at baseline, smoking asthmatics (N = 123) had higher ACQ6 (p < 0.0001) and lower asthma control (p = 0.021) than non-smoking asthmatics. Treatment with BDP/F HFA pMDI was associated with significant (p < 0.0001) improvements in pulmonary function (+7.1% in FEV1% pred), ACQ6 (-1.32) and GINA asthma control (improvement of control in 49.8% of patients). Importantly, the same treatment benefits were observed in former or current smokers compared with non-smoking asthmatics. There was a reduction in the dose of ICS from 489 ± 192 μg BDP extrafine equivalents at baseline to 265 ± 125 μg after one year. The drug was well-tolerated.. This prospective cohort study demonstrates the real-life effectiveness and safety of BDP/F HFA in adult asthma patients, including smokers, in normal clinical practice.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Smoking; Treatment Outcome

Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy.. This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.. Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.. Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.. clinicaltrials.gov NCT00497237.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Prospective Studies; Young Adult

Short-acting beta2-agonists like salbutamol and terbutaline are used as rescue medications for acute bronchoconstriction and relief of symptoms due to their rapid onset of action. The aim of this study was to assess whether inhaled beclomethasone dipropionate (BDP)/formoterol fumarate (FF) combination in extrafine formulation is non-inferior to salbutamol in the speed of reverting methacholine-induced bronchoconstriction and symptoms.. Fifty-six asthmatic patients were examined in a multicentre, randomised, double blind, double dummy, active treatment and placebo controlled three period cross-over study. On three different days, a single dose of BDP/FF 100/6 μg in pressurised metered-dose inhaler (pMDI) extrafine formulation or salbutamol 200 μg pMDI or placebo was inhaled after FEV(1) had dropped by 30-45% with methacholine challenge.. The median time to recovery of FEV(1) to 85% of baseline was similar for BDP/FF and salbutamol (3.66 and 2.15 min, respectively), but significantly longer for placebo (21.1 min). The planned analysis on adjusted mean time to recovery showed that the difference from methacholine-induced bronchoconstriction between BDP/FF and salbutamol was 3.82 min (95% confidence interval: -0.85 to 8.5), therefore greater than 3 min supposed in the study design. The difference between BDP/FF and salbutamol was not clinically significant. The two active treatments were also comparable in terms of the relief of symptoms (as assessed by the Borg dyspnoea scale).. BDP/FF combination has a fast onset of action, similar to that of salbutamol, and may represent a good alternative as rescue medication in asthmatic patients.

Topics: Adult; Albuterol; Asthma; Beclomethasone; Bronchial Spasm; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Methacholine Chloride; Middle Aged

Impulse oscillometry (IOS) provides an alternative method of assessing pulmonary function to conventional spirometry.. To compare the sensitivities of IOS and spirometry in assessing bronchoconstriction to propranolol and bronchodilation with salbutamol.. A post-hoc analysis of a randomized placebo-controlled crossover study was performed. Patients with mild-to-moderate persistent stable asthma taking 1,000 μg/day or less beclomethasone dipropionate equivalent received 10 or 20 mg of oral propranolol followed by histamine challenge, with recovery to nebulized salbutamol (5 mg). Spirometry and IOS were measured before and 2 hours after beta-blocker, post histamine, and 20 minutes post-salbutamol. Pre versus post percent change (95%CI) values were compared, and standardized response means (SRM) were calculated to assess the "signal to noise" of each test.. Thirteen participants (mean age, 34 years) completed the protocol. Eleven participants received 20 mg of propranolol; 2 received 10 mg, because this dose caused more than 10% decrease in forced expiratory volume in 1 second (FEV(1)) on the test-dose algorithm. All IOS indices (R5, R5-R20, AX, RF) showed significant worsening of airways resistance or reactance to propranolol. FEV(1) but not FEF25-75 showed significant deterioration after beta-blocker (mean percent change, 4.6% and 6.2%). The magnitude of change was consistently higher for parameters of IOS, with the largest change being observed with R5 and RF (mean percent change, 30.8% and 39.4%). The SRMs for IOS outcomes were better than for spirometry. All measures of lung function showed significant bronchodilator response, with the best SRMs seen in R5 and RF.. IOS is a more sensitive response outcome than spirometry with respect to bronchoconstriction to oral propranolol and bronchodilatation after salbutamol in patients with mild to moderate asthma.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Adult; Airway Resistance; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Cross-Over Studies; Female; Histamine; Humans; Lung; Male; Middle Aged; Oscillometry; Propranolol; Respiratory Function Tests; Spirometry; Treatment Outcome; Young Adult

Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.. In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329.. 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)-555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, p=0·03), combined (31%, 21-43, p=0·07), and rescue (35%, 24-47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5·6% (1·6-14) in the combined (p=0·012), 2·8% (0-10) in the daily (p=0·009), and 8·5% (2-15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.. Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided.. National Heart, Lung and Blood Institute.

Topics: Administration, Inhalation; Adolescent; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Disease Progression; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Kaplan-Meier Estimate; Male; Prednisone

Asthma guidelines suggest that normal or near normal lung function should be one of the goals for good asthma control. Therefore, children with chronic persistent asthma and reduced peripheral airway function were assessed after the replacement of conventional inhaled corticosteroids (ICS) with an extrafine aerosol formulation, hydrofluoroalkane-134a beclomethoasone diproprionate (HFA-BDP).. Lung function and clinical details were studied in children with moderate persistent asthma who regularly attended the pediatric pulmonary outpatient clinic at Kosair Children's Hospital, Louisville, Kentucky, USA.. A total of 20 children, 7 girls and 13 boys, with stable asthma but reduced forced expiratory flows between 25% and 75% of vital capacity (FEF(25-75) ) were included in the study.. After the initial assessment, each subject was switched from conventional ICS to HFA-BDP. All other medications remained the same. Reassessment of lung function and clinical status was performed at least 3 weeks after the intervention.. FEF(25-75) increased from a mean of 50.75% to 68.85% predicted (P < 0.001). Forced expiratory volume in 1 sec (FEV(1)) also increased significantly from 84.6% to 93.8% predicted (P = 0.001). No changes asthma symptoms were observed.. Compared to conventional ICS, the use of HFA-BDP in asthmatic children significantly improves airflow in both the large and the peripheral airways without loss of asthma control.

Topics: Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Female; Humans; Hydrocarbons, Fluorinated; Lung; Male; Respiratory Function Tests; Retrospective Studies

The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.. Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 μg per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.. At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p = 0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p = 0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.. Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma.. Clinicaltrials.gov identifier: NCT00463827.

Topics: Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Atorvastatin; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Heptanoic Acids; Humans; Male; Peak Expiratory Flow Rate; Pyrroles; Quality of Life; Smoking; Surveys and Questionnaires; Treatment Outcome

Beclomethasone dipropionate-hydrofluoroalkane (BDP-HFA) is a non-chlorofluorocarbon (CFC)-propelled metered dose inhaler. Data is needed to support the registration of BDP-HFA in pediatric populations for countries in the European Union.. The aim of the study was to assess short-term lower leg growth in children with asthma during treatment with BDP-HFA 100 μg BID compared with BDP-CFC 200 μg BID.. Children with asthma were included in this open-label, randomized, crossover study with 2-week run-in, active treatment, and washout periods. Lower leg length was measured every second week. As a secondary outcome parameter, 24-hour urine was collected for assessment of free cortisol. Interventions were inhaled BDP-HFA 100 μg BID with AeroChamber Plus spacer and BDP-CFC 200 μg BID with Volumatic spacer.. In 63 patients with asthma aged 5 to 11 years, BDP-HFA 100 μg BID was noninferior to BDP-CFC 200 μg BID, as the lower margin of CI (-0.03 to 0.10 mm/wk) of the estimated difference (0.03 mm/wk) was greater than the prespecified lower limit for noninferiority of -0.12 mm/wk. Mean (SD) lower leg growth rate during run-in, BDP-HFA 100 μg BID, and BDP-CFC 200 μg BID was 0.36 (0.17), 0.27 (0.21), and 0.23 (0.18) mm/wk, respectively (BDP-HFA estimate of difference, -0.09 [95% CI, -0.16 to -0.03 mm/wk; P < 0.01]; BDP-CFC estimate of difference, -0.13 [95% CI, -0.19 to -0.06 mm/wk; P < 0.001]). No statistically significant differences were seen in urinary free cortisol assessments. Eight and 6 mild to moderate adverse events in 10 children were reported during treatment with BDP-HFA and BDP-CFC, respectively. One event in each group was judged to be probably related to the study medication; no others were judged to be related.. No statistically significant differences were found in lower leg growth between BDP-HFA 100 μg BID with AeroChamber Plus spacer and BDP-CFC 200 μg BID with Volumatic spacer during 2-week treatment. Evidence of differences in systemic activity between the treatments was not found. EudraCT registration: 2007-007455-14.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chlorofluorocarbons; Cross-Over Studies; Female; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Leg; Male; Metered Dose Inhalers; Treatment Outcome

Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.. To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.. The percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.. A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Respiratory Sounds; Severity of Illness Index; Treatment Outcome

The dose-dependent anti-inflammatory effects of a recent fixed combination of extrafine beclomethasone dipropionate/formoterol (BDP/F) were investigated using non-invasive markers of inflammation, exhaled nitric oxide (NO) and adenosine monophosphate (AMP) provocative challenge. The aim was to assess the onset of the anti-inflammatory action of low and high doses and evaluate the suitability of non-invasive assessments to demonstrate dose response.. Steroid naïve adult out-patients with mild asthma, sensitive to AMP with baseline exhaled NO > 25 parts per billion entered a double-blind, placebo-controlled, 3-way, cross-over study. Patients were randomised to low dose (1 actuation) or high dose (4 actuations) extrafine BDP/F 100/6 μg, or placebo administered twice daily on Days 1 and 2 and once in the morning on Day 3 of each period. Exhaled NO was measured pre-dose on Day 1, then 2 and 4 hours post-administration on Day 3. The AMP challenge was performed 4 hours post-administration on Day 3 and forced expiratory volume in 1 second (FEV1, L) was measured from 0 to 4 hours post-dose on Day 1. Endpoints were NO at 2 and 4 hours, AMP challenge at 4 hours after the fifth dose on Day 3 and FEV1 area under the curve from 0 to 4 h post-dose on Day 1. Analysis of covariance was performed for NO and FEV1 and analysis of variance for AMP challenge.. Eighteen patients were randomised and completed the study. Exhaled NO was significantly lower for both doses of extrafine BDP/F versus placebo at 2 and 4 hours (high dose LS mean difference: -22.5 ppb, p < 0.0001 and -20.5 ppb, p < 0.0001; low dose: -14.1 ppb, p = 0.0006 and -12.1 ppb, p = 0.0043) with a significant dose response (p = 0.0342 and p = 0.0423). Likewise, AMP challenge revealed statistically significant differences between both doses of extrafine BDP/F and placebo (high dose LS mean difference: 4.8 mg/mL, p < 0.0001; low dose: 3.7 mg/mL, p < 0.0001), and a significant dose response (p = 0.0185). FEV1 was significantly improved versus placebo for both doses (high dose LS mean difference: 0.2 L, p = 0.0001; low dose: 0.2 L p = 0.0001), but without a significant dose response.. The fixed combination inhaler of extrafine BDP/F has early dose-dependent anti-inflammatory effects with a rapid onset of bronchodilatation in mild asthmatic patients.. ClinicalTrials.gov: NCT01343745.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoconstriction; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Metered Dose Inhalers; Middle Aged; Treatment Outcome; Young Adult

Long acting beta(2)-agonists (LABA) are widely used in children with asthma. Data from adults suggest that there is tachyphylaxis particularly to the bronchoprotective effects of LABA. There are no data in children. To determine whether LABA are subject to tachyphylaxis in school-aged children. Children were eligible for participation if they remained symptomatic on 400 microg of beclometasone dipropionate equivalent/day. Participants undertook a 4-wk run in period with open-label fluticasone 100 microg BD via Diskus. Children were then randomized to receive fluticasone 100 microg BD or salmeterol/fluticasone 50/100 microg BD via Diskus in a double-blind manner. Children underwent spirometry, cold air challenge and salbutamol reversibility testing at baseline, 4 and 8 wk. 37/42 children completed the study. There were significant improvements in basal FEV1 (% predicted) in the salmeterol/fluticasone group (n = 21) (+6.4% (95% CI: 2.4-10.5) p = 0.0033) but not in the fluticasone group (n = 16) [+1.2 (95% CI: -3.4 to 5.8) p = 0.5900]. There was a non-significant reduction in fall in FEV1 provoked by cold air in both groups. There was a significant lessening in the acute salbutamol response after 8 wk in the salmeterol/fluticasone group [-11.4% (95% CI: -17.6 to -5.2) p = 0.0010] but not in the fluticasone group [-1.6% (95% CI: -9.8 to 6.6) p = 0.6827]. Salmeterol/fluticasone therapy significantly improves basal FEV(1) in asthmatic children however, there is negligible additional bronchoprotection by week 4 of treatment and there is significant attenuation of salbutamol responsiveness when compared with fluticasone alone. Some of this reduction in salbutamol response may relate to the concurrent improvements in baseline lung function.

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Salmeterol Xinafoate; Tachyphylaxis; Treatment Outcome

The article was designed to estimate the effect of active and passive household cigarette smoke exposure on asthma severity and obstetric and neonatal outcomes in pregnant women with asthma.. We used a secondary observational analysis of pregnant women with mild and moderate-severe asthma enrolled in a prospective observational cohort study of asthma in pregnancy and a randomized clinical trial (RCT) comparing inhaled beclomethasone and oral theophylline. A baseline questionnaire detailing smoking history and passive household smoke exposure was given to each patient. Smoking status was confirmed in the RCT using cotinine levels. Data on asthma severity and obstetric and neonatal outcomes were collected and analyzed with respect to self-reported tobacco smoke exposure. Kruskal-Wallis and Pearson chi(2) statistics were used to test for significance.. A total of 2,210 women were enrolled: 1,812 in the observational study and 398 in the RCT. Four hundred and eight (18%) women reported current active smoking. Of the nonsmokers, 790 (36%) women reported passive household smoke exposure. Active smoking was associated with more total symptomatic days (P < .001) and nights of sleep disturbance (P < .001). Among the newborns of active smokers, there was a greater risk of small for gestational age < 10th percentile (P < .001), and a lower mean birth weight (P < .001). There were no differences in symptom exacerbation or outcome between nonsmokers with and without passive household cigarette smoke exposure.. Among pregnant women with asthma, active but not passive smoking is associated with increased asthma symptoms and fetal growth abnormalities.

Topics: Administration, Inhalation; Administration, Oral; Adult; Asthma; Beclomethasone; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant, Newborn; Maternal Exposure; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Severity of Illness Index; Smoking; Surveys and Questionnaires; Theophylline; Tobacco Smoke Pollution; Young Adult

Poor adherence to asthma controller medications results in poor treatment outcomes.. To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma randomized to one of two different treatment decision-making models or to usual care.. In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. The otherwise identical intervention protocols both provided asthma education and involved two in-person and three brief phone encounters.. Refill adherence was measured using continuous medication acquisition (CMA) indices-the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In follow-up Year 1, compared with usual care, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.46; P < 0.0001) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.40; P = 0.0225); higher cumulative controller medication dose (canister equivalent, 10.9 vs. 5.2; P < 0.0001); significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function). In Year 2, compared with usual care, SDM resulted in significantly lower rescue medication use, the sole clinical outcome available for that year. Compared with clinician decision making, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.59; P = 0.03) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.41; P = 0.0143); higher cumulative controller dose (CMA, 10.9 vs. 9.1; P = 0.005); and quantitatively, but not significantly, better outcomes on all clinical measures.. Negotiating patients' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes. Clinical trials registered with www.clinicaltrials.gov (NCT00217945 and NCT00149526).

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cromolyn Sodium; Decision Making; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Compliance; Patient Education as Topic; Patient Participation; Patient Satisfaction; Physician-Patient Relations; Quality of Life; Respiratory Function Tests; Surveys and Questionnaires; Theophylline; Treatment Outcome

When inhaling medication, it is essential that drug particles are delivered to all sites of lung inflammation, including the peripheral airways. The aim of this study was to assess the lung deposition and lung distribution of beclomethasone dipropionate (BDP)/formoterol (100/6 microg), both dissolved in hydrofluoroalkane (HFA) and delivered by pressurized metered dose inhaler (pMDI) in healthy subjects, asthmatic, and chronic obstructive pulmonary disease (COPD) patients, to investigate how the in vitro characteristics of the formulation translate into the in vivo performance in diseases with different airway obstruction.. Healthy volunteers (n = 8), persistent asthmatics (n = 8), and patients with stable COPD (n = 8) completed this open-label, single-dose parallel-group study. Each patient received one single treatment of four puffs of (99 m)Tc-labeled BDP/formoterol formulation. The correlation between particle size distribution of radioactivity and of the drugs in the radiolabeled formulation was validated. Intra- and extrapulmonary deposition, amount of exhaled drug, and the central to peripheral ratio (C/P) were calculated immediately after inhalation. Patients' lung function and pharmacokinetic parameters were also assessed up to 24 h post-dose.. The average lung deposition of BDP/formoterol was 34.08 +/- 9.30% (relative to nominal dose) in healthy subjects, 30.86 +/- 8.89% in asthmatics, and 33.10 +/- 8.90% in COPD patients. Extrathoracic deposition was 53.48% +/- 8.95, 57.64% +/- 9.92 and 54.98% +/- 7.01, respectively. C/P ratios of 1.42 +/- 0.32 in healthy subjects, 1.96 +/- 0.43 in asthmatics, and 1.94 +/- 0.69 for COPD patients confirmed drug distribution to all regions of the lungs. Forced expiratory volume in 1 sec (FEV(1)) increased in all groups after BDP/formoterol inhalation, but was more evident in the patient groups. No significant correlation between baseline lung function and drug deposition was observed. Formoterol, BDP, and beclomethasone 17 monopropionate (B17MP) plasma profiles were comparable between groups.. Inhalation of BDP/formoterol HFA (100/6 microg) produces high and homogeneous deposition of BDP and formoterol in the airways, regardless of pathophysiological condition.

Topics: Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Case-Control Studies; Drug Combinations; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tissue Distribution

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways.. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function.. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed.. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters.. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchi; Bronchioles; Chemistry, Pharmaceutical; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Pilot Projects; Respiratory Function Tests

Asthma treatment costs are substantial, the largest proportion being incurred by medications. Combination therapy with inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) is recommended in patients not adequately controlled by ICS alone. Aim of this study was to compare costs and health outcomes of a fixed ICS-LABA combination of beclomethasone dipropionate (BDP) and formoterol fumarate (FF) vs the same drugs delivered via separate inhalers in Germany.. A cost-minimization analysis, a cost-effectiveness analysis, as well as a threshold analysis were undertaken. Efficacy results were obtained from a recent clinical trial. Cost inputs include medical costs, physician costs, and hospital admission costs. Medical costs, health outcomes, and treatment costs were also varied to assess their impact on results.. Beclomethasone dipropionate/FF fixed combination was less costly compared to BDP + FF delivered as separate inhalers, costs totaling euro 525 and euro 637, respectively, over a 24-week treatment period. The incremental cost-effectiveness ratio was euro-9.77 per additional day free of asthma symptoms. Equal cost-effectiveness ratios would still be obtained at a price of the fixed combination increased by 3.4-fold.. A cost-minimization analysis as well as a cost-effectiveness analysis for Germany based on different product price calculations show that BDP/FF fixed combination is superior to BDP + FF delivered via separate inhalers.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cost-Benefit Analysis; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Germany; Health Care Costs; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome; Young Adult

Few studies on the concomitant effects of beclomethasone dipropionate and asthma-related factors on the growth of prepubertal asthmatic children have been published to date. In this prospective long-term 'real-life' cohort study we recruited 82 prepubertal steroid-naïve asthmatic patients aged 3 + years, excluding those with birth weight lower than 2500 g, malnutrition, and other concurrent chronic diseases. Height/age and weight/age Z scores were calculated every three months. Random effects multivariate longitudinal data analysis was used to adjust height/age and weight/age Z scores with independent variables. Among the studied patients, 63.4% were male, aged 4.7 + or - 1.5 years, 68.3% suffered from severe persistent asthma and had normal values for height/age and weight/age Z scores at enrolment. They were followed for 5.2 years (range 2.3-6.1) and used a mean daily beclomethasone dipropionate dose of 351.8 mcg (range 137.3-1140.0). Height/age and weight/age Z scores were not affected by either duration of treatment or doses of beclomethasone dipropionate up to 500 mcg, 750 mcg and higher than 750 mcg (p-values > 0.17). The multivariate analysis final model showed that severe persistent asthma was associated to lower height for age Z score (p = 0.04), whereas hospitalizations because of acute asthma (before and during follow-up) were associated (p = 0.02) to lower weight for age Z score. Growth parameters were not affected by the use of beclomethasone dipropionate.

Topics: Administration, Inhalation; Anthropometry; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Child; Child, Preschool; Female; Follow-Up Studies; Growth; Humans; Male; Multivariate Analysis; Prospective Studies; Time Factors

The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics.. Nine subjects with mild untreated allergic asthma performed two allergen challenges, after 1-week treatment with beclomethasone dipropionate (BDP, 500 microg b.i.d) or placebo. Forced Expiratory Volume in one second 1 (FEV1) was monitored to assess EAR and LAR, and uLTE4 was measured before and during EAR and LAR.. After placebo, uLTE4 increased significantly during EAR, but not during and after LAR, in comparison with baseline values. Beclomethasone dipropionate induced a significant attenuation of the uLTE4 increase during EAR, in comparison with placebo, in association with a good protection of LAR (P = 0.002) and a mild protection of EAR (P = 0.07).. Beclomethasone dipropionate blunts the early increase in uLTE4 excretion due to allergen challenge, in association with a significant effect on the severity of LAR. These data support the hypothesis that inhaled CS may inhibit the allergen-induced release of cys-LTs in asthma.

Topics: Administration, Inhalation; Adult; Allergens; Asthma; Beclomethasone; Chromatography, High Pressure Liquid; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Leukotriene E4; Male; Spirometry; Time Factors; Young Adult

Bronchial hyperresponsiveness to 5-adenosine mono-phosphate (AMP) is a marker of airway inflammation. Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma. To find out if these two drugs exert their protection in an additive fashion, we compared the effects of acute treatment with inhaled beclomethasone (BDP) and montelukast (ML), alone or in combination, on methacholine and AMP induced bronchoconstriction. 15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP, alone or in combination, in a randomized, double-blind, double-dummy placebo-controlled, crossover design. BDP pretreatment significantly increased the AMP PC(20) value (68.34+/-15.9mg/mL) as compared to placebo (22.87+/-5.7mg/mL). Combined treatment, BDP plus ML, afforded a further significant increase of AMP PC(20) (154.57+/-55.0mg/mL) as compared to each single treatment. The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC(20) doubling dose as compared to placebo and each single active treatment. Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides; Treatment Outcome; Young Adult

Small airways inflammation in asthma has been supposed to contribute to instability of the disease and therapy resistance. This study was designed to determine the validity of measurement of N(epsilon)-(carboxymethyl)lysine (CML) levels in induced sputum and alveolar concentrations of nitric oxide (NO) for the assessment of small airways inflammation in asthma.. The authors measured CML levels in induced sputum and the bronchial flux (Jno) and alveolar concentration (C(alv)) of NO in 37 asthmatic patients and 15 normal controls. After initial analysis, all asthmatics were randomly assigned to receive inhaled fluticasone propionate (FP; 400 microg/day, n = 21) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP; 400 microg/day, n = 16) for 12 weeks. And then the determination of exhaled NO level and sputum induction was performed after the treatment period.. CML levels in induced sputum were significantly higher in asthmatics than in normal controls (median [interquartile range], asthmatics: 53.0 [44.8-64.3] microg/ml, normal controls: 22.0 [14.8-28.3] microg/ml; p < .01). Similarly, Jno and C(alv) were also higher in asthmatics. Moreover, CML level was closely correlated with C(alv) but not with Jno in asthmatics (r = .47, p = .005). Jno was significantly correlated with forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), and CML level and C(alv) were correlated with forced expiratory flow between 25% and 75% of FVC (FEF(25-75)), an index of small airways obstruction. After FP treatment, the decrease in CML level and Calv were very small. In contrast, these levels were markedly decreased after HFA-BDP treatment. Moreover, even after FP or HFA-BDP treatment, CML level was significantly correlated with C(alv).. This novel, noninvasive technique of measurement of CML levels in induced sputum and C(alv) may prove to be important not only in the evaluation of small airways inflammation but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bronchi; Female; Fluticasone; Humans; Inflammation; Lysine; Male; Middle Aged; Nitric Oxide; Pulmonary Alveoli; Reproducibility of Results; Sputum

The effectiveness of pediatric asthma management programs in reducing health services utilization during exacerbations in developing countries is not widely studied. This study was carried out to assess the effectiveness of an asthma management program to reduce the overall health services utilization by acute asthma in children and adolescents.. In this historical population-based real-life cohort study, we selected 582 patients with asthma aged 4-15 living in deprived areas in the town of Itabira, Brazil, of which 470 cases were assisted by the asthma management program and 112 were controls. The end point was the first physician-diagnosed asthma exacerbation occurring after study enrollment and within 12 months after admission. All 470 cases received a written plan about exacerbation self-management, including the use of inhaled albuterol at home. Three hundred and seventeen out of 470 cases (67.4%) were also treated with beclomethasone diproprionate (BDP).. Both groups were comparable regarding gender, age group, and place of residence. At the end of the study, only 5% of cases vs 34% of controls did seek health services because of acute asthma (P < 0.01). Statistical difference also remained when comparing the 112 controls with the 153 cases not treated with com BDP (Hazard Ratio = 0.04, 95% CI, 0.01-0.14, P < 0.01).. Results have demonstrated the effectiveness of the pediatric asthma management program in reducing dependence on the health services for acute asthma. Effectiveness was also observed in subjects with no use of BDP.

Topics: Acute Disease; Adolescent; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Child; Child, Preschool; Cohort Studies; Female; Health Services; Humans; Male; Patient Education as Topic; Poverty; Self Care

Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.. In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison).. The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthma-control days, with a difference of 0.079 (P=0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P=0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P=0.003).. When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Cholinergic Antagonists; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adult; Aged; Airway Obstruction; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Germany; Humans; Lung Volume Measurements; Male; Metered Dose Inhalers; Middle Aged

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cost Savings; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Drug Costs; Ethanolamines; Female; Formoterol Fumarate; Germany; Humans; Male; Metered Dose Inhalers; Middle Aged; National Health Programs; Young Adult

Asthma morbidity is high, partly due to low adherence to inhaled corticosteroids (ICS). This study aims to assess rates and factors related to low adherence to ICS over time in asthmatic children and adolescents.. A concurrent cohort study was carried out for 24 months in 168 randomly selected patients suffering from persistent moderate asthma. All of them were given beclomethasone dipropionate (BDP) free of charge. Adherence rates were verified by pharmacy records (doses filled/doses prescribed). A multivariate analysis evaluated factors related with low adherence rates.. Overall adherence rates were 72.5, 58.6 and 61.1% in the 4th, 12th and 24th months of follow-up, respectively. Factors associated to adherence rates <70% were: mother's schooling level (p = 0.03), replacement of the caregiver (p = 0.03), prescription greater than two puffs/day (p = 0.005), absence of rhinosinusitis (p = 0.002) and age under 7 years (p = 0.04). Only the number of consultations lower than two in a 4-month period was associated to a lower adherence rate in all study periods (p = 0.02).. Adherence rates decreased over time, even in patients who had received the medication free of charge, and factors related to lower adherence changed during the follow-up. Results have shown that adherence had a dynamic pattern and its determinants should be re-evaluated continuously. Only the number of consultations was associated to a lower adherence rate in all periods, pointing out that health programs must recognize and facilitate the access of patients needing special care, which can contribute for better adherence and reducing asthma morbidity.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Child; Child, Preschool; Female; Glucocorticoids; Humans; Infant; Male; Medication Adherence; Multivariate Analysis; Prospective Studies; Treatment Outcome

Lung deposition is crucial for asthma treatment. However, there is no study comparing the potential role of lung co-deposition of combination therapy (inhaled corticosteroid and long-acting beta2 agonist) in the same inhaler. In moderate to severe asthmatics, an extra-fine hydrofluoroalkane combination of beclomethasone dipropionate and formoterol given via a single pressurised metered-dose inhaler (pMDI) was compared with beclomethasone dipropionate chlorofluorocarbon (CFC) pMDI and formoterol dry powder inhaler (DPI) given via separate inhalers.. In a double-blind, double-dummy, 24-week randomised clinical trial, 645 patients with moderate to severe asthma uncontrolled by regular treatment with inhaled corticosteroids received regular treatment with extra-fine fixed combination beclomethasone dipropionate 200 microg/formoterol 12 microg bid, or beclomethasone dipropionate (500 microg bid) via CFC pMDI and formoterol (12 microg bid) via DPI, or beclomethasone dipropionate (500 microg bid) via CFC pMDI. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included lung function measured at clinic, asthma symptoms and control, exacerbations.. Beclomethasone dipropionate/formoterol combination via single inhaler or via separate inhalers improved morning PEF. However, the combination via single inhaler was more effective than given via separate inhalers for asthma control. Both combination treatments were superior to beclomethasone dipropionate alone in improving lung function and asthma control. All treatments were well tolerated.. In patients with moderate to severe asthma, beclomethasone dipropionate/formoterol in a single inhaler was as effective as beclomethasone dipropionate plus formoterol and superior to beclomethasone dipropionate alone in improving lung function. For the first time with a single inhaler, beclomethasone dipropionate/formoterol was significantly superior to separate components for asthma control.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Formoterol Fumarate; Humans; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 microg day(-1)), theophylline (400 mg day(-1)) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L min(-1), 95% confidence intervals (CI) 10.9-68.8) and ACQ score (-0.47, 95% CI -0.91- -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13-342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99- -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Respiratory Function Tests; Smoking; Statistics, Nonparametric; Theophylline; Treatment Outcome

Active cigarette smoking has detrimental effects on asthma morbidity and severity. Angiopoietin-1 has been shown to protect the microvessels against plasma leakage, whereas angiopoietin-2 enhances vascular permeability and subsequently induces airway mucosal oedema. Therefore, it is recently thought that angiopoietin-2 may contribute to the pathophysiology of asthma.. To determine whether angiopoietin-2 levels in the airways are associated with clinical profiles in smoking asthmatics.. We measured angiopoietin-1 and -2 levels in induced sputum in 35 normal controls (18 non-smokers and 17 smokers) and 49 asthmatics (24 non-smokers and 25 smokers) before and after inhaled beclomethasone dipropionate (BDP: 800 microg/day) therapy for 12 weeks.. Angiopoietin-1 and -2 levels in induced sputum were significantly higher in asthmatics than in normal controls. Moreover, angiopoietin-2 levels were significantly higher in smoking asthmatics than in non-smoking asthmatics (P=0.0001). The airway vascular permeability index was also higher in smoking asthmatics than in non-smoking asthmatics. Moreover, the angiopoietin-2 level was positively correlated with the airway vascular permeability index (non-smoking asthmatics: r=0.87, P<0.001, smoking asthmatics: r=0.64, P=0.002). After BDP therapy, angiopoietin-1 levels were significantly decreased in non-smoking asthmatics, smoking-cessation asthmatics, and active-smoking asthmatics. In contrast, angiopoietin-2 levels did not differ from before to after BDP therapy in non-smoking asthmatics and active-smoking asthmatics. However, its levels were significantly decreased from before to after BDP therapy in smoking-cessation asthmatics (P=0.002). Although forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) before BDP therapy was comparable in all subgroups, this parameter after BDP therapy was significantly lower in active-smoking asthmatics than in non-smoking and smoking-cessation asthmatics. Moreover, the reduction in angiopoietin-2 levels after BDP therapy in smoking-cessation asthmatics was significantly correlated with an improvement in FEV(1)/FVC.. Angiopoietin-2 levels were elevated in the airways of smoking asthmatics, and its levels were associated with impaired airway responses.

Topics: Adult; Angiopoietin-1; Angiopoietin-2; Anti-Asthmatic Agents; Asthma; Beclomethasone; Capillary Permeability; Edema; Female; Forced Expiratory Volume; Humans; Male; Respiratory Mucosa; Smoking; Smoking Cessation; Sputum

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

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

Small airways appear to have an important role in asthma. Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) has ultrafine particles and accordingly greater deposition in the small airways than chlorofluorocarbon (CFC)-BDP. Impulse oscillometry systems (IOS), a new and non-invasive measure of pulmonary function, can examine the resistance of total (R5), large (R20), and small airways (R5-R20) separately, and low-frequency reactance area (AX), also considered a measure of small airways dysfunction.. Mild-to-moderate asthmatics who were inhaled corticosteroid naïve were randomized to receive 200 mcg HFA-BDP bid (n 1/4 26) or 400 mcg CFC-BDP bid (n 1/4 12) for 12 weeks in an open-label manner. Following baseline measurements, IOS and spirometry were repeated every 4 weeks, and methacholine challenge to separately assess airway sensitivity and airway reactivity and lung volumes at 12 weeks.. Moderate correlations were found between R5-R20 or AX and spirometry and lung volume indices of small airways, and between R20 and peak expiratory flow at baseline. The two groups did not significantly differ in baseline clinical or functional parameters. At 12 weeks, all IOS indices improved in the HFA-BDP group, whereas all but R5-R20 improved with CFC-BDP. R5-R20 and AX progressively improved with HFA-BDP; these changes achieved statistical significance at 12 weeks versus the CFC-BDP group. Other IOS and spirometry indices failed to show such trends. HFA-BDP significantly attenuated methacholine airway sensitivity; the degree of this attenuation strongly correlated with R5-R20 and AX baseline values, and with improvement of AX with treatment.. HFA-BDP is an effective treatment of small airways in asthma. Prolonged treatment provides a progressive effect over time, which is associated with an attenuation of airway responsiveness.

Topics: Adrenal Cortex Hormones; Adult; Airway Resistance; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Lung Volume Measurements; Male; Methacholine Chloride; Middle Aged; Muscarinic Agonists; Nebulizers and Vaporizers; Oscillometry; Respiratory Function Tests; Respiratory System; Spirometry

Loratadine added to montelukast has been suggested to improve endpoints of asthma.. This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV(1))-predicted of 50% to 85%, FEV(1) reversibility > or = 15%, and a minimal level of daytime symptoms and beta -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 mu g. A subsequent 48-week extension study compared montelukast + loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV(1).. Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV(1) were seen for montelukast + loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast + loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast + loratadine versus montelukast (1.60%). Significant improvements for montelukast + loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast + loratadine versus loratadine. In the extension study, both montelukast + loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences.. In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Beclomethasone; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Loratadine; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Young Adult

Asthma exacerbations are unpredictable, disruptive, and frightening, and are therefore important to prevent.. We investigated whether a policy of quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate reduces asthma exacerbations requiring treatment with oral corticosteroids.. A total of 403 people with asthma were given a self-management plan and randomized to take an active or placebo corticosteroid inhaler in addition to their usual asthma treatment when their PEF fell by 15% on 2 consecutive days or by 30% on 1 day. The study inhalers provided a quadrupling or no change in corticosteroid dose.. Eighteen of 197 (9%) and 29 of 203 (14%) participants had an exacerbation of asthma requiring treatment with oral corticosteroids in the active and placebo groups, respectively, giving a risk ratio of 0.64 (95% confidence interval, 0.37-1.11, P = 0.11). Of the 94 participants who started the study inhaler far fewer required treatment with oral corticosteroids in the active compared with the placebo group: 12 of 56 (21%) in the active group and 19 of 38 (50%) in the placebo group, giving a risk ratio of 0.43 (95% confidence interval, 0.24-0.78, P = 0.004).. Although our primary outcome did not reach statistical significance, quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate appears to reduce acute exacerbations of asthma and deserves further investigation. Clinical trial registered with www.controlled-trials.com (ISRCTN 46018181).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome

To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI) for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI) in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 microg once-daily (QD) for children aged 4-11 years.. Children (N = 233) aged 4-11 years were randomized to 52 weeks of treatment with MF-DPI 200 microg QD AM, MF-DPI 100 microg twice daily (BID), or BDP-MDI 168 microg BID. Patients had used inhaled corticosteroids (ICSs) daily for > or = 30 days before the screening visit and were on stable ICS doses for > or = 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations), vital signs, and physical examination.. The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%-49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 microg QD AM, 8%; MF-DPI 100 microg BID, 4%; BDP-MDI 168 microg BID, 2%) and oral candidiasis (4% in each treatment group). No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group.. Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 microg BID.

Topics: Administration, Inhalation; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Humans; Hydrocortisone; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols

International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze.. Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1-4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 microg beclomethasone bid plus 2500 microg salbutamol prn; (2) placebo bid plus 800 microg beclomethasone/1600 microg salbutamol combination prn; (3) placebo bid plus 2500 microg salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency.. As compared with prn salbutamol (61.0 +/- 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes.. Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study.

Topics: Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Infant; Male; Nebulizers and Vaporizers; Respiratory Sounds; Treatment Outcome

Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid.. In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00200967.. After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8-31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0-32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg-Gly/Gly] -0.1, -14.4 to 14.2; p=0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p<0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p=0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43-2.21, p=0.0038). Seven Arg/Arg participants (placebo, n=5; salmeterol, n=2) and six Gly/Gly participants (placebo, n=3; salmeterol, n=3) had an asthma exacerbation. Five serious adverse events were reported, one each during the pre-match and run-in phases on open-label inhaled corticosteroid, two during double-blind treatment with salmeterol/inhaled corticosteroid, and one during double-blind treatment with placebo/inhaled corticosteroid. None of the serious events was asthma-related or related to study drugs or procedures.. In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine.. National Institutes of Health.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Beclomethasone; Cross-Over Studies; Double-Blind Method; Female; Genotype; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Treatment Outcome

Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma.. To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC).. In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period.. Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment.. The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Breath Tests; Child; Cross-Over Studies; Dinoprost; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrogen Peroxide; Inflammation; Interleukins; Male; Nitrates; Nitric Oxide; Nitrites; Prospective Studies; Treatment Outcome; Vital Capacity

Rhinitis and asthma are currently recognized as manifestations of a single syndrome, the chronic allergic respiratory syndrome. Nearly all individuals with asthma have rhinitis, and severe rhinitis has been associated with worse outcomes in asthma patients. Intranasal treatment has been reported to be beneficial for the lower airways.. This was a randomized, double-blind, placebo-controlled study. The objective was to evaluate the effects that treatment with intranasal beclomethasone dipropionate (BDP; 400 microg/d) has on nasal and bronchial symptoms, as well as on lung function test results and bronchial responsiveness to histamine in patients with allergic rhinitis and asthma. We evaluated 33 patients, divided into two groups: treatment (n = 17); and placebo (n = 16). Over the course of the 125-day study period, each patient reported daily rhinitis and asthma symptoms, as well as the need for additional medication. All patients were submitted to spirometry and histamine challenge at baseline and at each subsequent evaluation (on days 50 and 75).. In comparison with the patients in the placebo group, those in the BDP treatment group presented significantly fewer nasal symptoms on day 50 and fewer asthma symptoms on day 75 (p < 0.01 for both); required rescue medications less often; and presented a significantly lower degree of bronchial responsiveness to histamine on day 75 (p < 0.01).. In this study, intranasal BDP was effective in treating rhinitis as well as asthma. The benefits for the lower airways were observed only after prolonged treatment and might be better evaluated through nonspecific bronchial challenge.

Topics: Administration, Intranasal; Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Female; Glucocorticoids; Histamine; Humans; Male; Respiratory Function Tests; Rhinitis; Young Adult

Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation.. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma.. Adults (>or=18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 micro g/day (n = 785) or beclomethasone dipropionate 640 micro g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of >or= 0.5 for nuclear opalescence, >or= 0.8 for cortical opacification, or >or= 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period.. Mean changes (+/- standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 micro g/day: 0.10 +/- 0.02, 0.07 +/- 0.02 and 0.04 +/- 0.01, respectively; beclomethasone dipropionate 640 micro g/day: 0.11 +/- 0.02, 0.09 +/- 0.02 and 0.03 +/- 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 micro g/day was non-inferior to beclomethasone dipropionate 640 micro g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820-1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values.. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 micro g/day or beclomethasone dipropionate 640 micro g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Asthma; Beclomethasone; Cataract; Double-Blind Method; Female; Glucocorticoids; Humans; Lens, Crystalline; Male; Middle Aged; Pregnenediones; Young Adult

To compare the effects of inhaled corticosteroids (ICS) and oral leukotriene modifier (LTM) montelukast on the prognosis of children with cough variant asthma (CVA), and to identify the related risk factors for the development of classic asthma in children with CVA.. Eighty-four children with CVA (2 - 6 yrs) were randomized to receive inhaled beclomethasone dipropionate 200 microg/d through pressurized metered-dose inhaler (MDI) plus spacer with mask or oral montelukast 5 mg, once at bedtime for 6 months, then followed by 18 months observation period after the end of the study medication.. There was no significant difference in antitussive days between the two groups (ICS group: 14 +/- 9 days, LTM group: 13 +/- 9 days, Z = 1.12, P = 0.25). Wheezing developed in 7.1% of the children in ICS group during 24 months follow-up period, which was significantly lower than that in LTM group (33.3%, chi2 = 8.92, P = 0.003). The prevalence of eczema or allergic rhinitis was higher in children who developed wheezing than those who did not develop wheezing (eczema: 47.1% vs. 19.4%, chi(2) = 4.16, P = 0.042; allergic rhinitis: 58.8% vs. 31.3%, chi2 = 4.40, P = 0.036). Logistic regression analysis confirmed that eczema and allergic rhinitis were risk factors for wheezing development in children with CVA, the odds ratio was 7.668 and 3.855 respectively (P < 0.05 for all). But administration of ICS was negatively correlated with the development of wheezing by an odds ratio of 0.128 (P = 0.008).. Children with CVA may progress to classic asthma; eczema and allergic rhinitis are two risk factors for wheezing development in children with CVA. Both ICS and LTM are effective antitussive treatment, but ICS may be more effective than LTM on preventing the progression of CVA to classic asthma.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cough; Cyclopropanes; Female; Follow-Up Studies; Humans; Male; Quinolines; Risk Factors; Sulfides; Treatment Outcome

To assess the effectiveness of a non-pharmacological intervention in patients with asthma on conventional therapy including inhaled corticosteroid.. A randomised controlled trial of the Buteyko technique in a group of adults with asthma. The control group was trained by a physiotherapist in breathing and relaxation techniques.. A single centre associated with a University-based asthma programme.. Asthma control, defined by a composite score based on the Canadian asthma consensus report 6 months after completion of the intervention.. Both groups showed substantial and similar improvement and a high proportion with asthma control 6 months after completion of the intervention. In the Buteyko group the proportion with asthma control increased from 40% to 79% and in the control group from 44% to 72%. In addition the Buteyko group had significantly reduced their inhaled corticosteroid therapy compared with the control group (p=0.02). None of the other differences between the groups at 6 months were significant.. Six months after completion of the interventions, a large majority of subjects in each group displayed control of their asthma with the additional benefit of reduction in inhaled corticosteroid use in the Buteyko group. The Buteyko technique, an established and widely recognised intervention, or an intensive programme delivered by a chest physiotherapist appear to provide additional benefit for adult patients with asthma who are being treated with inhaled corticosteroid.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Breathing Exercises; Bronchodilator Agents; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Physical Therapy Modalities; Treatment Outcome

The corticosteroid beclomethasone dipropionate (BDP) has been formulated with the long acting beta agonist formoterol (BDP/formoterol 100 microg/6 microg, Foster) in a single inhaler using Modulite technology. We have investigated the acute tolerability of high, cumulative doses of BDP/formoterol compared to formoterol alone and placebo. This was a double blind, 3-way cross-over comparison of 10 puffs of BDP/formoterol 100 microg/6 microg or formoterol 6 microg or placebo during maintenance treatment with BDP/formoterol two puffs per day. Pharmacokinetics over 12h during maintenance treatment was measured on day 7. High cumulative doses were then administered on three separated days. Eighteen patients with asthma were recruited (mean FEV(1) 65% predicted). The primary endpoint was serum potassium over the 12h period after high doses. QTc, blood pressure and heart rate over 12h, and plasma lactate and glucose over 3h following dosing were assessed. Formoterol caused a significantly greater decrease in serum potassium than BDP/formoterol or placebo (difference in mean minimum concentrations; 0.11 and -0.15 mmol/l, respectively, p<0.05 for both comparisons). No significant differences in serum potassium parameters were found between BDP/formoterol and placebo. QTc, plasma lactate and vital signs values observed with the combination were not statistically different from those with formoterol alone. For glucose, the mean maximum increase after formoterol treatment was 0.4 mmol/l (p<0.01 compared to placebo), while BDP/formoterol treatment caused a maximum increase of 0.7 mmol/l (p<0.01 compared to formoterol and placebo). The active metabolite of BDP is beclomethasone-17-monopropriate (B17MP), which reached Cmax at 0.25 h, with an elimination half-life of 3.7 h. Formoterol also reached Cmax at 0.25 h, and concentrations were measurable up to 12 h. High doses of BDP/formoterol did not significantly reduce serum potassium, while formoterol alone did to a greater extent. The BDP/formoterol combination was well tolerated, and exhibited a safety profile generally similar to formoterol alone when administered in high doses to stable asthmatic patients.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Glucose; Blood Pressure; Cross-Over Studies; Double-Blind Method; Drug Combinations; Electrocardiography; Ethanolamines; Female; Formoterol Fumarate; Half-Life; Heart Function Tests; Heart Rate; Humans; Lactic Acid; Male; Middle Aged; Potassium

Inhaled glucocorticosteroids are usually administered in two equal daily doses. To simplify the method of treatment, once-daily administration has been used. However, little information regarding whether once-daily treatment can sufficiently control airway inflammation is available. We aimed to investigate whether once-daily administration of inhaled glucocorticosteroids can control airway inflammation.. Twenty-four well-controlled asthma patients were enrolled in a randomized crossover trial to compare the efficacies of once-daily and twice-daily administration of inhaled glucocorticosteroids. Initially, the patients were randomly assigned to receive either once-daily or twice-daily administration for 16 weeks. After an 8-week washout period, patients who originally received twice-daily administration were assigned to once-daily administration for 16 weeks and vice versa. We assessed the changes in the forced expiratory volume in 1s, morning and evening peak expiratory flows, asthma symptoms, health-related quality of life and fractional exhaled nitric oxide levels.. Patients with once-daily administration showed the same level of clinical control and lung functions as patients receiving twice-daily administration. There was no difference in the fractional exhaled nitric oxide levels between the beginning and end of the twice-daily treatment (35.69 and 33.23ppb, respectively). In contrast, the fractional exhaled nitric oxide level was significantly higher at the end of the once-daily treatment (33.87 and 39.38ppb, respectively, p< 0.001).. Although once-daily administration is sufficient for clinical control of asthma, it might not control airway inflammation sufficiently.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Breath Tests; Budesonide; Cross-Over Studies; Drug Administration Schedule; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Quality of Life

To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus.. Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period.. The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study.. HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Eosinophil Cationic Protein; Eosinophilia; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Quality of Life; Sputum

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 microg plus formoterol 12 microg b.i.d. delivered via a pMDI or budesonide 400 microg plus formoterol 12 microg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain.. To compare the anti-inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid.. Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra-fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2-week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests.. Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14-0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9-15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P=0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests.. Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.

Topics: Acetates; Administration, Topical; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cetirizine; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Administration Routes; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quinolines; Rhinitis, Allergic, Perennial; Sulfides

Air trapping reflects small airway obstruction in asthma and can be assessed quantitatively by high-resolution computed tomography (HRCT). Hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) is deposited across all sizes of airways, including the small ones. However, its long-term effect on air trapping remains unknown in uncontrolled asthma.. To compare the effect of inhaled corticosteroids of different particle size - HFA-BDP and fluticasone propionate (FP) - on lung attenuation in mild-to-moderate uncontrolled asthma.. A randomized study was performed to analyze the effect of HFA-BDP (400 microg/d) or FP (500 microg/d) given over a period of 3 months to patients with uncontrolled mild-to-moderate asthma. HRCT was performed with spirometric gating, and lung attenuation was measured at residual volume and at pulmonary total capacity. The difference between inspiratory and expiratory attenuation was calculated as an air trapping index.. Twenty-five out of 58 patients had abnormal air trapping and could be included in the study. Lung attenuation significantly diminished in the posterior zones of the lung after a 3-month treatment with HFA-BDP or FP, but the difference between the groups was not significant. Adjusted mean variations of the air trapping index from baseline to treatment completion were 34.3 (11.2, 57.3) and 27.3 (6.4, 48.2) for the HFA-BDP and FP groups, respectively. However, the reduction of air trapping area was more pronounced in the group treated with HFA-BDP.. Inhaled corticosteroids decrease air trapping in uncontrolled asthma regardless of their particle size.. In mild-to-moderate asthma, air trapping assessed by HRCT may be a new outcome related to the control of the disease.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Airway Obstruction; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchospirometry; Female; Humans; Lung; Male; Particle Size; Tomography, X-Ray Computed; Treatment Outcome

One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.. To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.. In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.. Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.. In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

Topics: Acetates; Adult; Asthma; Beclomethasone; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Quality of Life; Quinolines; Respiratory Function Tests; Smoking; Sulfides; Treatment Outcome

Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids.. To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks).. Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control.. Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Clinical Trials as Topic; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Treatment Outcome

Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.

Topics: Administration, Inhalation; Aerosols; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Quality of Life; Respiratory Mechanics; Treatment Outcome

Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease (COPD) exacerbations. The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD. A total of 82 patients with COPD were randomised into two groups. One group was treated according to traditional guidelines (British Thoracic Society (BTS) group) and the other (sputum group) was treated with the additional aim of minimising eosinophilic airway inflammation, assessed using the induced sputum eosinophil count. The primary outcome was exacerbations, which were categorised as mild, moderate or severe. The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups, respectively (mean reduction 62%). The majority of this benefit was confined to patients with eosinophilic airway inflammation. There was no difference in the frequency of mild and moderate exacerbations. The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups. Out of 42 patients in the sputum group, 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation. A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Eosinophilia; Female; Glucocorticoids; Humans; Inflammation; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Sputum; Treatment Outcome

To assess the therapeutic effects of oral zileuton tablets combined with low-dose beclomethasone compared to doubling the dose of beclomethasone, in improving lung function and reducing asthma symptoms.. Randomized, active-control, double-blind, parallel, multi-center study of zileuton (400 or 600 mg QID)+200 microg beclomethasone dipropionate (BDP) BID versus placebo+BDP 400 microg BID in asthmatics with baseline FEV(1) percent predicted values between 40% and 80% following a single-blind ICS (BDP 200 microg BID) 2-week run-in. During the 3-month double-blind treatment period, assessments included safety, daytime and nighttime symptoms, acute asthma exacerbations, beta(2)-agonist use, AM and PM peak expiratory flow (PEF) and FEV(1).. The addition of a 5-lipoxygenase (5-LO) inhibitor added to a low-dose of BDP showed no significant difference in FEV(1) compared to doubling the dose of BDP. FEV(1) improved in all 3 treatment groups, with mean increases of 10% with zileuton 600 mg QID+BDP 200 microg BID, 12% with zileuton 400mg QID+BDP 200 microg BID, and 11% with BDP 400 microg BID by study end. Within each treatment group, there were significant improvements in asthma symptoms and AM and PM PEF compared to baseline. No significant differences were observed between groups with regards to salbutamol use, acute asthma exacerbations, the requirement for oral/parenteral corticosteroids and adverse clinical events.. The addition of a 5-LO inhibitor added to low-dose beclomethasone may be an alternative to higher-doses of ICS in patients unable to achieve sufficient asthma control on low-dose ICS therapy.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Hydroxyurea; Middle Aged; Peak Expiratory Flow Rate; Severity of Illness Index; Single-Blind Method

Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma.. We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed.. The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment.. Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].).

Topics: Adrenergic beta-Agonists; Adult; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Bronchoscopy; Catheter Ablation; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Hyperthermia, Induced; Male; Middle Aged; Muscle, Smooth; Peak Expiratory Flow Rate; Quality of Life

For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes.. In a randomized single-blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 microm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17-BMP) were measured by liquid chromatography plus mass spectrometry.. Aerosols with MMADs of 1.5 microm, 2.5 microm, and 4.5 microm gave mean maximum concentrations (C(max)) of 17-BMP of 475 pg ml(-1), 1300 pg ml(-1), and 1161 pg ml(-1), respectively. The area under the curve (AUC) values of 17-BMP for MMADs of 1.5 microm, 2.5 microm, and 4.5 microm were 825 pg ml(-1) h, 2629 pg ml(-1) h, and 2276 pg ml(-1) h, respectively. The mean terminal half-time of 17-BMP for all three aerosol sizes was around 1.5 h.. Monodisperse BDP aerosols with a MMAD of 1.5 microm gave two-three fold lower values for C(max) and AUC than those with MMADs of 2.5 and 4.5 microm.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Anti-Asthmatic Agents; Area Under Curve; Asthma; Beclomethasone; Biological Availability; Cross-Over Studies; Female; Humans; Male; Middle Aged; Particle Size; Single-Blind Method

Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma. We investigated whether the symptom-driven use of a combination of beclomethasone dipropionate and albuterol (also known as salbutamol) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol.. We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive one of four inhaled treatments: placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed (as-needed combination therapy); placebo twice daily plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed (regular beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed (regular combination therapy). The primary outcome was the morning peak expiratory flow rate.. In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher (P=0.04) and the number of exacerbations during the 6-month treatment was lower (P=0.002) in the as-needed combination therapy group than in the as-needed albuterol therapy group, but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy. The cumulative dose of inhaled beclomethasone was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy (P<0.001 for both comparisons).. In patients with mild asthma, the symptom-driven use of inhaled beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as effective as regular use of inhaled beclomethasone (250 microg twice daily) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid. (ClinicalTrials.gov number, NCT00382889 [ClinicalTrials.gov].).

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Combinations; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

Extra-fine particle formulations of hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC-BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation.. A double-blind randomized crossover trial was undertaken comparing the anti-inflammatory effects of HFA-BDP (100 and 400 microg/day) and CFC-BDP (200 and 800 microg/day). Treatment with montelukast was evaluated as add-on to the higher dose of BDP.. Compared with baseline after withdrawal of usual asthma therapy, 100 microg of HFA-BDP significantly attenuated serum eosinophilic cationic protein levels (0.61-fold change, 95% CI 0.49-0.77; a 39% reduction, P < 0.001), but 200 microg of CFC-BDP did not (0.87-fold change, 95% CI 0.63-1.23; P = 1). A dose of 800 microg of CFC-BDP and 400 microg of HFA-BDP led to reductions in exhaled nitric oxide (0.57-fold change, 95% CI 0.44-0.73; a 43% reduction, P < 0.001 and 0.65-fold change, 95% CI 0.47-0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (-74 cells/microl, 95% CI -146 to -2; P = 0.020 and -77 cells/microl, 95% CI -140 to -14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66-0.98; P = 0.028) with 400 microg HFA-BDP and eosinophils (-44 cells/microl, 95% CI -80 to -8; P = 0.012) with 800 microg CFC-BDP, but not vice versa.. Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.

Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Chlorofluorocarbons; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Humans; Hydrocarbons, Fluorinated; Inflammation; Nitric Oxide; Particle Size; Quinolines; Sulfides

Valved holding chambers improve delivery of inhaled corticosteroids to the lung but are bulky in design. A novel compact vortex actuator device has therefore been developed.. To compare the in vitro and in vivo performance of a novel compact vortex actuator (the Neohaler [NH]) vs a conventional small-volume valve holding chamber (the AeroChamber Plus [AP].. Seventeen asthmatic patients completed the study per protocol, receiving 4 weeks each of 100 microg/d (50-microg formulation) or 400 microg/d (100-microg formulation) of hydrofluoroalkane beclomethasone dipropionate via the NH or AP devices in a randomized crossover, double-blind, double-dummy, placebo-controlled design. The doubling dilution (dd) shift in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (primary outcome) was used to evaluate anti-inflammatory effects and adrenal function to measure systemic exposure. The fine particle (<4.7 tm) dose was evaluated using an Andersen Cascade Impactor.. A total of 100 microg of hydrofluoroalkane beclomethasone dipropionate via the NH and AP produced 0.95-dd (95% confidence interval [CI], 0.44-1.45; P = .006) and 0.45-dd (95% CI, -0.16 to 1.06; P = .83) improvements from baseline in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%, respectively, with no statistically significant difference between devices: 0.50 dd (95% CI, -0.25 to 1.24; P = .18). At 400 microg/d, 1.08-dd (95% CI, 0.49-1.67; P = .006) and 0.85-dd (95% CI, 0.32-1.39; P = .02) improvements were found for the NH and AP, respectively, with a 0.23-dd difference (95% CI, -0.28 to 0.74; P = .36) between devices. No adrenal suppression occurred with either device. The in vitro fine particle dose was 39.1 microg for the NH and 39.0 microg for the AP with the 100-microg formulation and 26.0 g and 25.2 microg, respectively, with the 50-microg formulation.. Delivering hydrofluoroalkane beclomethasone dipropionate via the NH and AP attenuates asthmatic airway inflammation to a comparable degree and produces a similar in vitro fine particle dose profile.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Nebulizers and Vaporizers

Compliance with long-term inhaled therapy in asthma is often poor, but it is likely to be improved with a simplified administration, once daily. The present study was designed to assess whether, in childhood asthma, a single dose of nebulized beclomethasone dipropionate once daily was as effective and safe as the same total daily dose administered twice daily.. Asthmatic children, not treated with inhaled steroids for at least a month preceding the study and using short-acting bronchodilators more than once a week were enrolled in a double-blind, double dummy, randomised, multicentric study. After a two week run-in period on nebulised twice daily 400 mcg beclomethasone dipropionate, patients were randomly assigned to twelve weeks of treatment with 800 mcg nebulised beclomethasone dipropionate daily, either in single dose (o.d. group) or divided into two 400 mcg doses (b.i.d. group).. 65 children (mean age 8.6 years, mean FEV1 81% of predicted), were valuable for intention to treat. During the run-in period, a significant improvement in FEV1, FVC, morning and evening PEF values and clinical scores was observed. Children then entered the randomised trial: 32 were included in the o.d. group and 33 in the b.i.d. group. During the twelve week treatment period, the observed improvement in pulmonary function parameters was maintained in both treatment groups. Morning and evening PEF showed a progressive slight increase as well as PEF diurnal variability showed a progressive reduction in the two treatment groups during the whole study period without reaching statistical significance. Moreover, in both treatment groups a similar progressive increase in symptom free nights and days and in the percentage of children achieving total asthma symptoms control was detected. Finally, no significant changes in urinary cortisol/creatinine ratio were observed throughout the study period and between groups.. A daily dose of 800 mcg of beclomethasone, administered for twelve weeks with a nebuliser either once or twice daily provide similar efficacy in maintaining pulmonary function and symptoms of asthmatic children, with a good tolerability profile.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Circadian Rhythm; Creatinine; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Nebulizers and Vaporizers; Patient Compliance; Peak Expiratory Flow Rate; Spirometry; Treatment Outcome; Vital Capacity

Inhaled corticosteroids are recommended as first-line therapy for the management of asthma, although side-effects may limit their use. Ciclesonide, a novel pro-drug inhaled corticosteroid, exerts potent and prolonged local anti-inflammatory effects in the lungs, and is considered to have an improved safety and tolerability profile. The aim of this study was to evaluate the efficacy and safety of ciclesonide in adult patients with mild to moderate asthma.. A placebo-controlled, multicentre, randomized, double-blind, parallel-group study was conducted. During the 4-week baseline period, patients were given 400 microg/day of beclomethasone dipropionate in a chlorofluorocarbon formulation. After the baseline period, 311 patients were given once-daily 100, 200 or 400 microg of ciclesonide or placebo for an 8-week treatment period without the use of a spacer. The primary efficacy variable was morning PEF.. Changes in the morning PEF (least squares mean) at the end of the study were 4.23 L/min (P < 0.001) in the 100 microg group, 3.75 L/min (P < 0.001) in the 200 microg group, -0.40 L/min (P < 0.001) in the 400 microg group, as compared with -24.95 L/min in the placebo group. In the ciclesonide groups, the PEF remained at the same level as the baseline period. No large differences were observed between the placebo group and the ciclesonide groups regarding safety.. Once-daily administration of ciclesonide at doses of 100, 200 or 400 microg was shown to be effective in adult patients with mild to moderate asthma. Ciclesonide is considered to have favourable safety profiles and be well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Least-Squares Analysis; Male; Pregnenediones; Spirometry; Vital Capacity

Inhaled corticosteroids are recognized as first-line therapy in the management of asthma; however, their use may be limited by systemic and local side-effects. Ciclesonide, a novel pro-drug inhaled corticosteroid, is activated in the lungs and is expected to have less systemic and local side-effects. This study evaluated the efficacy and safety of ciclesonide in hydrofluoroalkane (HFA) compared with beclomethasone dipropionate (BDP) in a chlorofluorocarbon (CFC) formulation in adult patients with moderate to severe asthma.. This was a multicentre, randomized, open-label, parallel-group comparative study. The patients were given 800 microg/day of CFC-BDP in the four-week baseline period. After the baseline period, 319 patients were randomly allocated into three groups which, respectively, received HFA-ciclesonide 400 microg/day (without a spacer), HFA-ciclesonide 800 microg/day (without spacer) and CFC-BDP 800 microg/day (with spacer) for the eight-week treatment period. The primary efficacy variable was morning PEF.. The morning PEF increased by 16.02 L/min in the 400 microg HFA-ciclesonide group, 23.98 L/min in the 800 microg HFA-ciclesonide group and 5.91 L/min in the 800 microg CFC-BDP group. Better outcomes were achieved by the use of 800 microg/day of HFA-ciclesonide compared with 800 microg/day of CFC-BDP (P = 0.001). There was no difference in adverse events between the groups.. In adult patients with moderate to severe asthma, 800 microg/day of HFA-ciclesonide was significantly more effective than 800 microg/day of CFC-BDP. Ciclesonide at doses of 400 microg/day and 800 microg/day was safe and well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Pregnenediones

It is important to evaluate the effects of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP), which shows predominant deposition in the lower airways, on asthmatic inflammation in the lower airways and the Quality of Life (QOL) of asthma patients, as compared with those of fluticasone propionate (FP) Diskus.. Seventy-seven adult patients with mild persistent or more severe asthma who were being treated with FP for >/=3 months were randomly assigned to the HFA-BDP group and continued FP group. The differential count of eosinophils in the peripheral blood, the serum cortisol levels, and pulmonary function parameters were measured before the study and at 3 months after the start of the study treatment. The improvements in the Asthma Quality of Life Questionnaire (AQLQ) scores were also compared. Sputum samples collected by the induced expectoration method (inhalation of 10% saline for 15 min) were divided into the early-phase sputum samples obtained within 15 minutes of the inhalation and the late-phase sputum samples obtained later than 15 minutes after the inhalation, and the eosinophil count and eosinophil cationic protein (ECP) levels were measured.. In the HFA-BDP group (N=40), the differential count of eosinophils in the peripheral blood was significantly decreased as compared with that in the FP group (p=0.009), and the scores in all the domains of the AQLQ and the percentage improvement of the total score were significantly better as compared with those in FP group (p=0.033). The eosinophil count in the late-phase sputum samples (p=0.022) as well as the ECP level in the sputum samples showed more pronounced decreases in the HFA-BDP group as compared with those in the FP group. On the other hand, no significant changes were detected in the pulmonary function values.. Use of the HFA-BDP preparation can more effectively suppress residual inflammation in the lower airways and significantly improve the QOL as compared with use of the FP preparation of asthma patients. Examination of induced sputum samples allows detection of changes in the peripheral airways that cannot be detected by pulmonary function testing.

Topics: Administration, Inhalation; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Middle Aged; Quality of Life

International guidelines advocate the early introduction of inhaled corticosteroids (ICS) in all types of persistent asthma. Our study was undertaken to assess the effects of ICS on bronchial hyperresponsiveness (BHR) as a hallmark of inflammation, and to assess the symptoms, the use of rescue medications, and the parameters of lung function in patients with mild intermittent asthma. The patients with intermittent asthma (n = 85) were randomly allocated to a treatment with ICS, beclomethasone dipropionate 250 microg/day and short-acting beta2 agonists salbutamol as needed (Group A, n = 45) or to a treatment with only short-acting beta2 agonists as needed (Group B, n = 40) during the 6-month treatment period. At the end of the study, in Group A, we found a statistically significant decrease of BHR (PD20 0.98 vs. 2.07) (p < 0.001), diurnal peak expiratory flow (PEF) variability (17.9 vs. 13.8) (p < 0.001), symptom scores (0.63 vs. 0.30) (p < 0.001), and used rescue medication (p < 0.001), while the parameters of lung function remained unchanged except for forced expiratory volume in 1 sec (FEV1), which had a statistically significant increase (3.58 vs. 3.66) (p < 0.001). In Group B, there was a statistically significant decrease of lung function parameters FEV1 (3.80 vs. 3.71) (p < 0.001), forced vital capacity (FVC) (4.43 vs. 4.37) (p < 0.001), FEV1/FVC (88.2 vs. 85.3) (p < 0.05), PEF (8.05 vs. 7.51) (p < 0.01), PEF variability (17.85 vs. 18.33) (p < 0.001), increased BHR (PD20 1.04 vs. 0.62) (p < 0.05), and symptom scores (0.46 vs. 0.62) (p < 0.01), as well as the use of rescue medication during the day (p < 0.001). Early introduction of low doses of ICS may be more beneficial than beta2 agonists alone in patients with intermittent asthma.

Topics: Adrenal Cortex Hormones; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Female; Humans; Male; Treatment Outcome

The aim of our study was to analyze the effect of recreational swimming on lung function and bronchial hyperresponsiveness (BHR) in patients with mild persistent asthma. This study included 65 patients with mild persistent asthma, who were divided into two groups: experimental group A (n = 45) and control group B (n = 20). Patients from both groups were treated with low doses of inhaled corticosteroids (ICS) and short-acting beta2 agonists salbutamol as needed. Our program for patients in group A was combined asthma education with swimming (twice a week on a 1-h basis for the following 6 months). At the end of the study, in Group A, we found a statistically significant increase of lung function parameters FEV1 (forced expiratory volume in 1 sec) (3.55 vs. 3.65) (p < 0.01), FVC (forced vital capacity) (4.27 vs. 4.37) (p < 0.05), PEF (peak expiratory flow) (7.08 vs. 7.46) (p < 0.01), and statistically significant decrease of BHR (PD20 0.58 vs. 2.01) (p < 0.001). In Group B, there was a statistically significant improvement of FEV1 3.29 vs. 3.33 (p < 0.05) and although FVC, FEV1/FVC, and PEF were improved, it was not significant. When Groups A and B were compared at the end of the study, there was a statistically significant difference of FVC (4.01 vs. 4.37), FEV1 (3.33 vs. 3.55), PEF (6.79 vs.7.46), and variability (p < 0.001), and statistically significantly decreased BHR in Group A (2.01 vs. 1.75) (p < 0.001). Engagement of patients with mild persistent asthma in recreational swimming in nonchlorinated pools, combined with regular medical treatment and education, leads to better improvement of their parameters of lung function and also to more significant decrease of their airway hyperresponsiveness compared to patients treated with traditional medicine.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Female; Histamine; Humans; Hypersensitivity, Immediate; Male; Patient Education as Topic; Respiratory Function Tests; Swimming

Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol.. This was a phase III, multinational, multicentre, double-blind, randomized, two-arm parallel groups, controlled study. After a 2-week run-in period, 228 patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler.. The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio.. The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368).

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Severity of Illness Index; Time Factors

Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.. To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400-1,000 mug of beclomethasone or equivalent).. Multicenter, randomized, double-blind, placebo-controlled study.. Morning peak expiratory flow, forced expiratory volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065).. Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia.

Topics: Administration, Inhalation; Adrenergic Agonists; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Injections, Intravenous; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Severity of Illness Index; Sputum; Treatment Failure

Coexisting asthma and allergic rhinitis (AR) are often treated with both intranasal and inhaled corticosteroids. This study investigated whether intranasal ciclesonide 200 microg once daily has an additional effect on cortisol suppression when coadministered with inhaled hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP). Adult patients (n = 150) with perennial AR received HFA-BDP 320 microg twice daily and placebo once daily during a run-in period. Patients were then randomized to ciclesonide or placebo and HFA-BDP (43 days). A single 2-mg dose of dexamethasone was administered on the last treatment day. Plasma cortisol decreased by 67.8 microg x h/dL (p < 0.001) during the run-in period. When ciclesonide was added, the change in mean plasma cortisol was similar for ciclesonide and placebo (8.5 microg x h/dL and 1.0 microg x h/dL, respectively). Dexamethasone decreased mean plasma cortisol (p < 0.001), demonstrating that further cortisol suppression was possible. This study suggests that intranasal ciclesonide can be used with an inhaled corticosteroid without increased cortisol suppression.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Pregnenediones; Rhinitis, Allergic, Perennial

The relatively new chlorofluorocarbon-free solution preparation of beclomethasone dipropionate in hydrofluoroalkane (HFA-BDP) (Qvar, 3M Pharmaceuticals) generates an extra fine aerosol with a smaller particle size (mean mass aerodynamic diameter of 1.1 microm), drug deposition in the lung is more uniformly distributed, thus improving efficacy even at a low dose. This might be also important for the use of a new fixed combination containing HFA-BDP plus formoterol in one inhaler for basic therapy and for an as-need application. Further, inhalation once a day might considerably enhance patients' adherence to maintenance therapy. The aim of this study was to test clinical efficacy and safety of twice daily inhalation (b.i.d.) vs. once daily inhalation (o.d.). In a double-blind, randomised, multicenter, parallel-group study, the efficacy and safety of 200 microg HFA-BDP o.d. (evenings) was compared with 100 microg HFA-BDP b.i.d., and with placebo. The trial included 201 patients with mild to moderately severe asthma. FEV1 was the primary endpoint and treatment duration was eight weeks. The improvement of FEV1 (20.4% o.d. vs. 12.9% b.i.d. vs. 7.9% placebo) was comparable in the two BDP groups. Both were more effective than placebo (P=0.014). The efficacy of o.d. dose was also equivalent to b.i.d. dose in secondary endpoints (peak flow, beta2-sympathomimetic drug use, asthma symptom score, and nocturnal awakenings). The treatment was well tolerated. A single evening dose (200 microg HFA-BDP) is as equivalently effective as the twice daily inhalation (2x100 microg HFA-BDP) in mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Germany; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Powders; Severity of Illness Index; Treatment Outcome

Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents available for the treatment of asthma but they produce only modest effects on airway inflammation and non-specific bronchial hyperresponsiveness (BHR). However, little is known about the possibility that treatment with ICS might cause additional protection on BHR to inhaled tachykinins such as neurokinin A (NKA).. Therefore, we compared the effects of beclomethasone dipropionate (BDP) on the degree of BHR to inhaled histamine and NKA in a double-blind, controlled, cross-over study of asthmatic patients.. Patients attended the laboratory before and after each 6 weeks treatment period to undertake concentration-response studies with histamine and NKA. Bronchial responsiveness to both funs was expressed as the provocative concentration producing a 20% decrease in FEV(1) from baseline (PC(20)).. BDP therapy attenuated the constrictor response to both agonists to a similar degree, their geometric mean (range) PC(20) values increasing from 0.47 (0.21-1.41) mg/ml to 2.43 (0.51-4.50) mg/ml (P<0.01, post-salb vs. post-BDP treatment) and from 101.7 (27.3-356.1) microg/ml to 666.7 (151.5-1,000) microg/ml (P<0.01, post-salb vs. post-BDP treatment) for histamine and NKA, respectively.. Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Histamine; Humans; Male; Neurokinin A; Statistics, Nonparametric

The study aims to assess the a priori hypothesis that regular supplementation with vitamin C or magnesium will permit a reduction in the corticosteroid dose required to maintain asthma control in adults.. We invited all participants recruited from primary care centres who completed a parallel-group, randomised, placebo-controlled, 16-week supplementation trial of 1g/day vitamin C or 450 mg/day magnesium to continue and participate in a structured corticosteroid reduction protocol over 10 weeks.. A total of 92 participants (29 vitamin C, 31 magnesium and 32 placebo) entered the study. Assuming no reduction in corticosteroid dose in the 10 who subsequently withdrew, the geometric mean reductions in inhaled corticosteroid dose achieved with vitamin C, magnesium and placebo were 49, 13 and 11 microg, respectively. Relative to placebo, the unadjusted effect of vitamin C was significant, and remained at borderline significance after adjustment for baseline corticosteroid dose (relative reduction ratio=4.03, 95% CI 0.95 to 17.1, P=0.06).. We conclude that while vitamin C supplements may have modest corticosteroid sparing effects and hence the potential to reduce exposure to their side effects, magnesium supplements have no effect on the inhaled corticosteroid dose required to maintain asthma control.

Topics: Administration, Inhalation; Adolescent; Adult; Ascorbic Acid; Asthma; Beclomethasone; Double-Blind Method; England; Female; Glucocorticoids; Humans; Magnesium; Male; Middle Aged; Vitamins

Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma.. In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored.. Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated.. Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aminopyridines; Anti-Inflammatory Agents; Asthma; Beclomethasone; Benzamides; Child; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Probability; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

The incidence of asthma has been positively associated with obesity. Asthma comprises diverse "phenotypes" reflecting heterogeneity in a number of characteristics, including response to therapy. The present authors examined whether body mass index (BMI) influenced the response to placebo, as well as to two asthma controller medications. A post hoc analysis was performed, pooling data from four double-blind, placebo-controlled studies randomising 3,073 moderate asthmatic adults to montelukast (n=1,439), beclomethasone (n=894) or placebo (n=740). The primary end point was asthma control days; other end points were forced expiratory volume in one second, beta-agonist use and nocturnal awakening. Analyses were conducted using BMI classification into normal (<25.0 kg.m-2; 52% of patients), overweight (25-29.9 kg.m-2; 32%) and obese (>or=30.0 kg.m-2; 16%) categories, as well as BMI as a continuous variable. The treatment groups were balanced for BMI, demographic characteristics and parameters of asthma control. The placebo response for all end points was generally lower with increasing BMI. Similarly, the response to the inhaled corticosteroid decreased, whereas the response to the leukotriene antagonist remained stable. In conclusion, post hoc data from the present study suggested that body mass index may influence the natural history of asthma control (as reflected by response to placebo) and may differentially influence response to the two active agents, warranting explicit testing in future prospective studies.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Mass Index; Cyclopropanes; Double-Blind Method; Female; Humans; Male; Middle Aged; Quinolines; Sulfides; Treatment Outcome

Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later.. To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo.. Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization.. Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment.. HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aerosol Propellants; Algorithms; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Budesonide; Cytokines; Double-Blind Method; Eosinophils; Female; Humans; Hydrocarbons, Fluorinated; Lymphocytes; Male; Powders; Sputum

Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest.. To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar).. Fifteen asthmatic patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV1 [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 microg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure.. The 2 formulations were equivalent in terms of predefined equivalence limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the 400-microg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant (P < .05) reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant (P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses (P < .05).. Beclate and Qvar were equivalent for all primary and secondary outcome measures.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Bronchoconstrictor Agents; Creatine; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nitric Oxide; Spirometry; Therapeutic Equivalency; Treatment Outcome

Antileukotrienes and inhaled corticosteroids are asthma controller agents widely used in the treatment of pediatric asthma.. To evaluate the effects of montelukast and beclomethasone on linear growth in prepubertal asthmatic children for 1 year.. This was a 30-center study of boys (6.4-9.4 years old) and girls (6.4-8.4 years old) at Tanner stage I with mild, persistent asthma. After a placebo run-in period, 360 patients were randomized in equal ratios to double-blind, double-dummy treatment with 5 mg of montelukast, 200 microg of beclomethasone twice daily (positive control), or placebo for 56 weeks; 90% of the patients completed the study. The primary end point was linear growth velocity, measured using a stadiometer.. Linear growth rates were similar between the montelukast and placebo groups; the mean difference for the year was 0.03 cm. The mean growth rate with beclomethasone was significantly less than with placebo (-0.78 cm) or montelukast (0.81 cm) (P < .001 for both). Median percentage of days with beta-agonist use was greater with placebo (14.58%) vs montelukast (10.55%) or beclomethasone (6.65%) (P < .05 for all). More patients used oral corticosteroid rescue with placebo (34.7%) than with montelukast (25.0%) or beclomethasone (23.5%). An imbalance in bone marker levels was seen with beclomethasone but not with montelukast.. In prepubertal asthmatic children, montelukast did not affect linear growth, whereas the growth rate with beclomethasone was significantly decreased during 1 year of treatment.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Child; Cyclopropanes; Double-Blind Method; Female; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

Topics: Administration, Cutaneous; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Asthma; Beclomethasone; Bronchodilator Agents; Child; Drug Therapy, Combination; Humans; Peak Expiratory Flow Rate; Terbutaline

The target of anti-inflammatory therapy in asthma is thought to be situated, at least partly, in the lung periphery, and inhaled steroid aerosols are being engineered to reach it. However, the potential effect of such aerosols cannot be fully evaluated by conventional lung function tests because these are insensitive to peripheral lung structure.. A prospective cohort study was conducted to investigate whether ultrafine steroid aerosols can elicit a response in the lung periphery, using a validated multibreath washout technique that can distinguish acinar from conductive lung zone function.. In 30 stable patients with asthma with a wide range of disease severity (FEV(1) 27% to 108% predicted), we assessed conductive and acinar airway function abnormality at baseline, with patients on a standard dry powder steroid aerosol and after switching them to an ultrafine steroid aerosol.. Only in those patients with abnormal acinar airway function at baseline (n = 16) did acinar heterogeneity show a consistent improvement after switching to an ultrafine steroid aerosol; the improvement was also correlated with baseline acinar heterogeneity (r = -0.67; P = .007). Although all patients with asthma also presented conductive airway abnormality at baseline, no changes were observed in this lung zone with the switch to the ultrafine aerosol (P > .1).. Among stable patients with asthma, those with acinar lung zone abnormality at baseline have the potential to receive functional benefit from an ultrafine steroid aerosol. Clinical studies comparing the efficacy of steroid aerosols targeted to the deep lung should at least include a measurement of peripheral lung zone function.. A new noninvasive measure of small airways function reveals why, and for which particular patients with asthma, small steroid aerosol particles can be of therapeutic use.

Topics: Adolescent; Adult; Aerosol Propellants; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Humans; Hydrocarbons, Fluorinated; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Powders; Spirometry

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bone Density; Bone Resorption; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Osteoporosis; Salmeterol Xinafoate

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.

Topics: Adrenergic beta-Agonists; Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Medical Records; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate

The treatment of bronchial asthma with QVAR (hydrofluoroalkane-134a BDP; 3M Pharmaceuticals, St. Paul, MN, USA) is usually conducted without an inhalation assistance device. However, Japanese patients who experience difficulty in coordinating activation with inspiration of inhaled steroid drugs are instructed on the use of such a device. We therefore examined the necessity of using an inhalation assistance device (INSPIR-EASE, IE) and its effect on quality of life (QOL) in the treatment of patients with bronchial asthma taking QVAR. Hence, lung function and QOL associated with taking QVAR plus IE or QVAR alone were examined by a cross-over method in 44 bronchial asthma patients (STEP 2 or 3) over 20 years of age. In all patients, lung function tests conducted 12 weeks after start of treatment indicated significant improvements of forced expiratory volume in 1 second (FEV1) with QVAR alone compared with QVAR plus IE (p < 0.05). In patients less than 70 years of age, significant improvements of forced vital capacity (FVC) and nitric oxide (NO) were also observed with QVAR alone compared with QVAR plus IE (p < 0.05). Examination of QOL the Living with Asthma Questionnaire indicated that medication usage was significantly improved with QVAR alone compared with QVAR plus IE. Significant improvement of FEV1 was observed with QVAR alone compared with QVAR plus IE, and additionally in patients less than 70 years of age improvement of FVC and NO was also marked. This study confirmed the usefulness of QVAR alone in patients with bronchial asthma.

Topics: Activities of Daily Living; Adult; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Nitric Oxide; Quality of Life; Treatment Outcome; Vital Capacity

Inhaled beclomethasone dipropionate (BDP) with the propellant hydrofluoroalkane-134a (HFA) has been designed to be equivalent in terms of safety to chlorofluorocarbon (CFC)-formulated metered dose inhalers (MDI). The aim was to assess whether BDP HFA MDI 100 microg twice daily was equivalent to BDP CFC MDI 100 microg twice daily in terms of effects on short-term lower leg growth rate (LLGR) and measures of hypothalamic-pituitary-adrenal (HPA) function. The study consisted of a randomized double-blind cross-over trial with three active, a run-in and two wash-out periods each consisting of 2 wk. The place of study was a secondary referral outpatient clinic. The subjects involved were 14 boys and 10 girls with asthma, aged 7-12 yr. They were all administered BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily. The outcome measures included LLGR and 24-h urine-free cortisol (UFC) and total cortisol metabolites (TCM). Mean (SD) LLGR during run-in and BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily periods were 0.43 (0.23), 0.09 (0.29), 0.10 (0.45) and 0.08 (0.27) mm/wk. The one-sided 97.5% confidence interval for the difference in LLGR between BDP HFA 100 microg and BDP CFC 100 microg was 0.24, thus, below the predefined criterion of 0.20 mm/week. Inter-period comparisons of active treatments showed no differences between means of LLGR, UFC or TCM. Though non-inferiority between BDP HFA and CFC 100 microg twice daily in terms of effects on LLGR was not found, equivalence was suggested by comparisons of LLGR during run-in and active treatments and by HPA function measures.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chlorofluorocarbons; Chlorofluorocarbons, Methane; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Hypothalamo-Hypophyseal System; Leg; Male; Pituitary-Adrenal System; Treatment Outcome

Cigarette smokers with asthma are insensitive to short term inhaled corticosteroid therapy, but efficacy when given for a longer duration at different doses is unknown.. Ninety five individuals with mild asthma were recruited to a multicentre, randomised, double blind, parallel group study comparing inhaled beclomethasone in doses of 400 microg or 2000 microg daily for 12 weeks in smokers and non-smokers. The primary end point was the change in morning peak expiratory flow (PEF). Secondary end points included evening PEF, use of reliever inhaler, number of asthma exacerbations, spirometric parameters, and asthma control score.. After 12 weeks of inhaled beclomethasone there was a considerable difference between the morning PEF measurements of smokers and non-smokers with asthma (-18 (95% CI -35 to -1), adjusted p = 0.035). Among those receiving 400 microg daily there was a difference between the mean (95% CI) morning PEF (l/min) in smokers and non-smokers (-25 (95% CI -45 to -4), adjusted p = 0.019) and in the number of asthma exacerbations (6 v 1 in smokers and non-smokers, respectively, p = 0.007). These differences were reduced between smokers and non-smokers receiving 2000 microg inhaled beclomethasone daily.. Compared with non-smokers, smokers with mild persistent asthma are insensitive to the therapeutic effect of low dose inhaled corticosteroid treatment administered for a 12 week period. The disparity of the response between smokers and non-smokers appears to be reduced with high dose inhaled corticosteroid. These findings have important implications for the management of individuals with mild asthma who smoke.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Smoking; Vital Capacity

Two postulated intrinsic anti-inflammatory mechanisms in asthma include the low affinity IgE receptor, or CD23, and interleukin 1 receptor antagonist (IL-1ra). We investigated the role these mediators play in the asthmatic response by measuring local levels in human asthmatics before and after segmental allergen challenge and examined the effect of inhaled corticosteroids on soluble CD23 and IL-1ra levels. Ten subjects underwent bronchoscopy at baseline and 24 hours after antigen challenge. Prior to challenge and every 12 hours afterward subjects received beclomethasone 252 microg or placebo. Fluid was analyzed for sCD23 and IL-1ra using ELISA immunoassays. Eosinophil percentages significantly increased at 24 hours following antigen challenge. sCD23 levels were generally undetectable at baseline and increased significantly following antigen challenge. IL-1ra levels increased 28-fold in the late-phase response. Beclomethasone significantly reduced the late-phase eosinophil percentage at 24 hours compared with placebo but did not attenuate late-phase sCD23 or IL-1ra levels. Our data showed a significant rise in the levels of two mediators thought to play an important role in the attenuation of the asthmatic response. The finding that steroid treatment did not enhance these levels suggests that this may be an independent approach to asthma therapy that should be investigated.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Cross-Over Studies; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; Humans; Male; Middle Aged; Receptors, IgE; Receptors, Interleukin-1

Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety.. In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use.. Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group.. Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eosinophils; Female; Glucocorticoids; Headache; Hoarseness; Humans; Hydrocortisone; Interleukin-5; Male; Middle Aged; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index; Theophylline; Treatment Outcome

Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.

Topics: Administration, Inhalation; Adult; Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Leukotriene Antagonists; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate; Respiratory Function Tests; Salmeterol Xinafoate

Metered inhalers using chlorofluorocarbon (CFC) propellents have been gradually replaced by new devices that use hydrofluoroalkanes (HFAs) as their propellents, which are less harmful to the environment. This reformulation led to a substantial improvement of the previous technologies applied to inhalation devices and of the physical characteristics of drugs delivered. In particular, inhaled corticosteroids, such as beclomethasone dipropionate (BDP) which is of fundamental importance in the long-term management of bronchial asthma, took advantage of this reformulation. Unlike the preparation beclomethasone dipropionate and chlorofluorocarbon (BDP-CFC) which was a suspension, that of beclomethasone dipropionate and a hydrofluoroalkane (BDP-HFA) is a solution and produces an aerosol with a mean aerodynamic particle size of 1.1 microm, which is much smaller than the particle size of 3.5-4.0 microm, obtained with the BDP-CFC. The particles of BDP-HFA can then deposit in the lungs in a larger amount, and particularly in the more peripheral airways where the inflammatory process starts in the case of bronchial asthma. A 12-week use of BDP-HFA ensured a significant better control of the bronchial response to methacholine (MCh) than the corresponding use of BDP-CFC for the same duration. The therapeutic performance of BDP-HFA proved much higher and allowed the substantial reduction of the therapeutic daily dose for the clinical asthma management, being the increased and more peripheral deposition of BDP-HFA is presumed to play a crucial role.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchi; Bronchoconstrictor Agents; Chlorofluorocarbons; Cross-Over Studies; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Methacholine Chloride; Middle Aged; Respiratory Function Tests

Although inhaled corticosteroids are useful and effective in the prophylaxis of childhood asthma, there is a dearth of information regarding the duration of treatment. The present study was undertaken to assess the possibility of successful withdrawal of inhaled corticosteroids in childhood asthma following good control of the disease.. The study was carried out at the Asiri Hospital, Colombo, Sri Lanka and was a prospective observational clinical study. The participants were consecutive children with documented moderately severe and severe asthma seen over a period of 4 years from January 1990 and followed up to December 2003. Patients were allocated randomly to receive either beclomethasone dipropionate or budesonide. Initial dose of the selected drug was 300, 400 or 600 microg/day, depending on the child's age. After a period of stabilization, the dose was reduced from the starting dose to a maintenance level of 200, 300 or 400 microg/day, respectively. Once sustained control had been maintained for a period ranging from 9 to 18 months, gradual withdrawal was attempted. The dosage was reduced by 50-100 microg each time, at intervals of 3 months. Long-term follow up was maintained following withdrawal of inhaled corticosteroids. Breakthrough wheezing, acute severe attacks, hospitalization for wheezing and absence from school were used to assess the response.. Eighty-six children were recruited into the study. Eighty children responded well. The initial period on a high dose of corticosteroid was 8.4 months (range 4-12 months) and the average period of maintenance dosing was 11.7 months (range 9-18 months). The average time taken for withdrawal was 12.6 months (range 9-18 months). Successful withdrawal was achieved in 73 children. In this group, the mean total duration of treatment was 27.4 months (range 20-44 months). Up to December 2003, the subjects had been observed for an average period of 97.1 months (range 86-121 months) following withdrawal of inhaled corticosteroids. Of the 73 children in whom corticosteroids were withdrawn, 57 (78%) have remained well without any episodes of wheezing, and 14 (19%) have had mild episodes of wheezing that were easily controlled by bronchodilators. No patient needed hospitalization, long-term treatment or systemic corticosteroids. In two (3%) patients, it was necessary to restart inhaled corticosteroids because of troublesome recurrences.. It is possible to gradually withdraw inhaled corticosteroids in a significant proportion of asthmatic children once good control has been sustained on a maintenance dose for a considerable period.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glucocorticoids; Humans; Infant; Male; Observation; Prospective Studies; Time Factors; Treatment Outcome

Mometasone furoate dry powder inhaler (MF-DPI) [400 mug] is an inhaled corticosteroid (ICS) that is effective in the treatment of asthma. MF-DPI has a low potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis at its clinical dose. The effect of MF-DPI, 400 microg qd, on the HPA axis was compared to that of beclomethasone dipropionate (BDP) using hydrofluoroalkane (HFA) and chlorofluorocarbon (CFC) propellants via metered-dose inhalers (MDIs) twice daily.. This randomized, third-party blind, parallel-group study compared the effects of MF-DPI 400 mug one puff qd in the morning (n = 18), HFA-BDP 200 microg two puffs MDI bid (n = 18), and CFC-BDP 400 microg two puffs MDI bid (n = 17) for 14 days on the area under the 24-h serum cortisol concentrations curve (AUC(0-24)) and on total 24-h urinary free cortisol excretion in mild asthmatic subjects. Effects on morning/evening peak expiratory flow (PEF) and on inhaled albuterol use were also assessed. Adverse events that occurred during or > or = 30 days after the study were recorded.. The mean decrease from baseline in the serum cortisol concentrations AUC(0-24) in the MF-DPI group was significantly less than in either the HFA-BDP (p = 0.024) or the CFC-BDP (p = 0.011) groups. Decreases in serum cortisol concentrations AUC(0-24) in the two BDP groups did not differ from one another. The MF-DPI group trended toward higher morning and evening PEF than either BDP group. Treatment-associated adverse events were reported by seven subjects in the MF-DPI group, vs one subject in the HFA-BDP and three subjects in the CFC-BDP groups; these were mild, and no subject discontinued treatment due to an adverse event.. Fourteen days of treatment with MF-DPI 400 microg qd was associated with a significantly lesser decrease in the serum cortisol concentrations AUC(0-24) compared with HFA-BDP 200 microg MDI or CFC-BDP 400 microg MDI bid.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Beclomethasone; Chlorofluorocarbons; Creatinine; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant, Newborn; Male; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Pregnadienediols

Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchodilator Agents; Chlorofluorocarbons; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Pharmaceutical Solutions; Pulmonary Ventilation; Single-Blind Method; Suspensions

Fourteen mild-to-moderate asthmatic patients completed a randomized four-way crossover scintigraphic study to determine the lung deposition of 200 microg budesonide inhaled from a Respimat Soft Mist Inhaler (Respimat SMI), 200 microg budesonide inhaled from a Turbuhaler dry powder inhaler (Turbuhaler DPI, used with fast and slow peak inhaled flow rates), and 250 microg beclomethasone dipropionate inhaled from a pressurized metered dose inhaler (Becloforte pMDI). Mean (range) whole lung deposition of drug from the Respimat SMI (51.6 [46-57]% of the metered dose) was significantly (p < 0.001) greater than that from the Turbuhaler DPI used with both fast and slow inhaled flow rates (28.5 [24-33]% and 17.8 [14-22]%, respectively) or from the Becloforte pMDI (8.9 [6-12]%). The deposition pattern within the lungs was more peripheral for Respimat SMI than for Turbuhaler DPI. The results of this study showed that Respimat SMI deposited corticosteroid more efficiently in the lungs than either of two widely used inhaler devices, Turbuhaler DPI or Becloforte pMDI.

Topics: Adult; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Equipment Design; Female; Forced Expiratory Volume; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Radiopharmaceuticals; Technetium

Rhinitis and asthma are considered to be synchronic or sequential forms of the same allergic syndrome. Treating the inflammation associated with allergic rhinitis influences the control of asthma. However, few studies have investigated the effect of treating perennial rhinitis on persistent asthma and vice versa. We determined the effects of inhaled or topical nasal beclomethasone dipropionate (BDP) administered separately or in combination on the control of asthma and bronchial hyperresponsiveness (BHR) in patients with the rhinitis/asthma association.. A double-blind, parallel, three-group study.. Outpatient clinic of Pulmonary Division/Heart Institute (InCor) and the Division of General Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil.. Seventy-four patients with mild-to-moderate asthma and allergic rhinitis (median age, 25 years).. Patients received nasal or inhaled BDP separately or in combination for 16 weeks after a 2-week placebo run-in period.. Nasal and pulmonary symptoms, as well as pulmonary function and BHR, were compared among the three groups after 4 weeks and 16 weeks of treatment. Patients in all three groups demonstrated a progressive and significant decrease in nasal and pulmonary symptoms, which started after 4 weeks (p < 0.05) and continued through the end of treatment (p < 0.001). Clinical improvement was similar and parallel in the three groups. Asthma-related morbidity, evaluated by quantifying absence from work, emergency department visits, and nighttime awakenings, also decreased in the three groups (p < 0.05).. Failure to consider treatment of rhinitis as essential to asthma management might impair clinical control of asthma. Furthermore, these data suggest that asthma and rhinitis in some patients can be controlled by the exclusive use of nasal medication.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Multivariate Analysis; Rhinitis, Allergic, Perennial

The objective of this study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP) from a breath-activated inhaler (QVAR Autohaler) compared with proper and improper press and breathe (QVAR P&B) metered dose inhaler (MDI) technique. The hypothesis was that that the smaller particles of BDP from HFA-BDP would stay suspended longer in the inspiratory air of patients and thus reduce the deleterious effects of inhaler discoordination. The study was an open label, four period, cross-over design. Asthmatic patients (n = 7) with a history of asthma symptoms, an FEV-1 of >70% of predicted normal, and a history of reversibility to a beta-agonist of >or=12% were utilized. BDP was radiolabeled with technetium-99m and delivered from the QVAR Autohaler or QVAR P&B device in patients trained to reproducibly utilize coordinated and discoordinated P&B MDI technique. Patients using Autohaler MDI exhibited 60% lung deposition of BDP. Patients using coordinated technique with the P&B MDI exhibited 59% lung deposition. Patients trained to consistently actuate the P&B MDI before inhaling exhibited 37% lung deposition. Patients trained to consistently actuate the P&B MDI late in the inspiration (i.e., 1.5 sec into a 3-sec inspiration) exhibited 50% lung deposition. In conclusion, the breath-activated Autohaler automatically provided optimal BDP lung deposition of 60%. Patients with good P&B MDI technique also received optimal lung deposition of 59%. The degree of lung deposition was decreased as patients demonstrated poor inhaler technique. However patients with poor technique still received a large lung dose of BDP (i.e., >or=37%) compared with lung deposition values of 4-7% for CFC-BDP MDIs previously published and confirmed in this study.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Cross-Over Studies; Drug Delivery Systems; Female; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Scintillation Counting; Technetium

Asthma self-management plans that include doubling the dose of inhaled corticosteroid when the condition deteriorates improve asthma control. Whether doubling the dose of corticosteroid in isolation is effective is unknown. We undertook a randomised controlled trial to investigate the effects of doubling the dose of inhaled corticosteriods when asthma deteriorates.. 390 individuals with asthma who were at risk of an exacerbation monitored their morning peak flow and asthma symptoms for up to 12 months. When peak flow or symptoms started to deteriorate, participants added an active or placebo corticosteroid inhaler to their usual corticosteroid for 14 days to produce a doubling or no change in dose. The primary outcome was the number of individuals starting oral prednisolone in each group.. During 12 months, 207 (53%) started their study inhaler and 46 (12%) started prednisolone--22 (11%) of 192 and 24 (12%) of 198 in the active and placebo groups, respectively. The risk ratio for starting prednisolone was therefore 0.95 (95% CI 0.55-1.64, p=0.8).. We recorded little evidence to support the widely recommended intervention of doubling the dose of inhaled corticosteroid when asthma control starts to deteriorate.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Metered Dose Inhalers; Middle Aged; Prednisolone; Treatment Outcome

Exhaled nitric oxide (FENO) measurements may be influenced by a number of confounding factors. Reports have offered conflicting evidence as to whether caffeine consumption increases or decreases FENO. In this study we aimed to confirm whether caffeine ingestion affects FENO in patients with asthma. On two separate days, 20 patients with asthma (10 steroid-naive and 10 steroid-treated) received a standard cup of either caffeinated or noncaffeinated coffee (15 g) (control) in a randomized, double-blind, cross-over manner. FENO measurements were obtained at baseline, and 30, 60, 120, and 180 minutes after ingestion. Serum caffeine levels were also measured at 0 and 60 minutes. No significant changes in FENO occurred after caffeine compared with the control. We conclude that caffeinated foods and beverages are unlikely to acutely influence FENO in subjects with asthma, and protocols for laboratory measurement do not need to take this factor into account.

Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bias; Breath Tests; Caffeine; Confounding Factors, Epidemiologic; Cross-Over Studies; Double-Blind Method; Feeding Behavior; Forced Expiratory Volume; Humans; Metabolic Clearance Rate; Middle Aged; Nitric Oxide; Sensitivity and Specificity; Time Factors

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.

Topics: Administration, Cutaneous; Administration, Inhalation; Adrenergic beta-Agonists; Aged; Androstadienes; Asthma; Beclomethasone; Bronchial Hyperreactivity; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Severity of Illness Index; Terbutaline; Time Factors; Treatment Outcome

This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention.. A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed.. There was no significant difference (P=.554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR]=0.9, 95% CI=0.6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR=0.3, 95% CI=0.1-0.9; P=.016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284+/-0.331 vs 0.284+/-0.221, P=.039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes.. The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Odds Ratio; Pregnancy; Pregnancy Complications; Severity of Illness Index; Theophylline; Treatment Outcome

To compare the systemic safety and efficacy of hydrofluoroalkane beclomethasone dipropionate (HFA-BDP) extra-fine aerosol 800 microg/day with chlorofluorocarbon (CFC)-BDP 1500 microg/day.. Six-month, randomized, parallel-group, double-blind, double-dummy study.. Patients (n=141) with moderate to severe asthma adequately controlled by CFC-BDP 1000 microg/day to 2000 microg/day.. Patients received CFC-BDP 1500 microg/day during a two-week run-in period and were then randomized to either HFA-BDP (n=70) or CFC-BDP (n=71).. Similar proportions of HFA-BDP and CFC-BDP patients had a 24 h urinary free cortisol values below the reference range at month 6 (15% versus 25%, P=0.35). Measures of adrenocorticotrophic hormone stimulation and morning plasma cortisol levels were also similar in each group. The frequency of skin bruising and oral candidiasis was low for both treatments. No change in intraocular pressure was reported for either treatment. Pulmonary function was similar in both groups; however, the onset of the first asthma exacerbation or increased asthma symptoms tended to be earlier for CFC-BDP than for HFA-BDP (P=0.076); 27% of CFC-BDP patients reported increased asthma symptoms, compared with 14% of HFA-BDP patients (P=0.095).. HFA-BDP 800 microg/day has a systemic adverse event profile comparable to that of CFC-BDP 1500 microg/day, and further control of asthma symptoms may be achieved after a switch from CFC-BDP 1500 microg/day to HFA-BDP 800 microg/day.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Respiratory Tract Infections; Treatment Outcome

To evaluate the effect of a humanized monoclonal antibody to immunoglobulin E, omalizumab (Xolair, Novartis Pharmaceuticals, East Hanover, NJ; Genentech Inc, South San Francisco, CA), on airway inflammation in asthma, as indicated by the fractional concentration of exhaled nitric oxide (FE(NO)), a noninvasive marker of airway inflammation. Xolair was approved recently by the US Food and Drug Administration for moderate-to-severe allergic asthma in adolescents and adults.. As an addendum at 2 sites to a randomized, multicenter double-blind, placebo-controlled trial, FE(NO) was assessed in children with allergic asthma over 1 year. There were 3 consecutive study periods: 1) stable dosing of inhaled beclomethasone dipropionate (BDP) when the dose was optimized (period of 16 weeks); 2) inhaled steroid-reduction phase (period of 12 weeks), during which BDP was tapered if subjects remained stable; and 3) open-label extension phase, during which subjects receiving placebo were switched to active omalizumab (period of 24 weeks). The primary outcome was area under the FE(NO) versus time curve (AUC) for adjusted FE(NO), defined as the ratio of FE(NO) at each time point compared with the value at baseline.. Twenty-nine subjects participated and were randomized to omalizumab (n = 18) and placebo (n = 11) treatment groups in a 2:1 ratio dictated by the main study. There was a significant difference for age, resulting in a difference in absolute forced expiratory volume in 1 second but no difference in asthma severity based on the forced expiratory volume in 1 second percentage predicted. Baseline BDP dose was comparable between groups, as were baseline values of mean FE(NO) (active: 38.6 +/- 25.6 ppb; placebo: 52.7 +/- 52.9 ppb). The degree of BDP dose reduction during the steroid-reduction and open-label phases was equivalent between the omalizumab and placebo-treated groups; subjects in the omalizumab- and placebo-treated groups had reduced their BDP dose by an average of 51% and 60%, respectively, at the end of the steroid-reduction phase and by 68% and 94%, respectively, by the end of the open-label period. In the active and placebo groups, 44% and 27% and 75% and 73% of subjects had stopped use of inhaled corticosteroids at the end of the steroid-reduction and open-label phases, respectively. There was no significant difference between the active and placebo groups during the steroid-stable phase for AUC of adjusted nitric oxide (1.31 +/- 1.511 vs 1.45 +/- 0.736). However, during the steroid-reduction phase, the variability of adjusted FE(NO) in the placebo-treated group was greater than that of the omalizumab-treated group at most visits, with a significant difference between groups for AUC of adjusted nitric oxide (0.88 +/- 0.69 vs 1.65 +/- 1.06). FE(NO) fell from 82.1 +/- 55.6 ppm at the end of the steroid-reduction phase to 33.3 +/- 21.6 ppb at the end of the open-label period in the placebo group who were placed on active omalizumab. This decrease occurred while the mean dose of BDP remained very low. Analysis of FE(NO) over 52 weeks of omalizumab treatment in the active group demonstrated that there was a significant reduction from baseline to the end of the open-label period (41.9 +/- 29.0 to 18.0 +/- 21.8 ppb) despite a high degree of steroid reduction.. In this preliminary study based on FE(NO), a noninvasive marker of airway inflammation, treatment with omalizumab may inhibit airway inflammation during steroid reduction in children with allergic asthma. The degree of inhibition of FE(NO) was similar to that seen for inhaled corticosteroids alone, suggesting an antiinflammatory action for this novel therapeutic agent in asthma. This is in keeping with recent evidence that omalizumab inhibits eosinophilic inflammation in induced sputum and endobronchial tissue.

Topics: Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Breath Tests; Child; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Immunoglobulin E; Male; Nitric Oxide; Omalizumab

To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma.. Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab.. One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP).. Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy.. Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks.. Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.

Topics: Adolescent; Adult; Aged; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Forecasting; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Respiratory Hypersensitivity; Treatment Outcome

Computed tomography studies demonstrate thickening of the asthmatic airway wall and its relation to disease severity. We evaluated the effect of inhaled corticosteroid on this phenomenon.. Cross-sectional images of the right upper lobe apical segmental bronchus were obtained by helical computed tomography in 45 corticosteroid-naïve patients with persistent asthma and 28 healthy controls. Airway wall thickness was measured as airway wall area normalized to body surface area. Computed tomography, pulmonary function, and serum levels of eosinophil cationic protein were examined before and after treatment with beclomethasone (800 microg/d for 12 weeks).. Before treatment, airway wall thickness was greater in asthma patients than in controls (P <0.0001). After treatment, it decreased by 11% (P <0.001) but remained high (P <0.0001 vs. control); the serum level of eosinophil cationic protein decreased, and airflow obstruction was reduced, but not to the level in controls. The decrease in wall thickness was associated with a decrease in the serum level of eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness was related to disease duration (r = 0.45, P = 0.003) and remaining airflow obstruction.. Wall thickening of asthmatic central airways responds partially to inhaled corticosteroid therapy and may reflect an overall reduction in airway inflammation. "Unresponsive components," possibly involving structural changes, may increase in the absence of inhaled corticosteroid treatment, potentially leading to chronic airflow obstruction.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Blood Proteins; Drug Administration Schedule; Eosinophil Granule Proteins; Female; Follow-Up Studies; Glucocorticoids; Humans; Lung; Male; Middle Aged; Respiratory Function Tests; Respiratory Mucosa; Ribonucleases; Time Factors; Tomography, X-Ray Computed

Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy and tolerability of omalizumab in patients with poorly controlled, moderate-to-severe allergic asthma.. This was a randomized, open-label, multicentre, parallel-group study. A total of 312 patients (12-73 years) receiving >/=400 microg/day (adolescent) or >/=800 microg/day (adult) inhaled beclomethasone dipropionate, or equivalent were included. Patients received best standard care (BSC) with or without omalizumab [at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks] for 12 months.. The annualized mean number of asthma deterioration-related incidents was reduced from 9.76 with BSC alone (n = 106) to 4.92 per patient-year with omalizumab (n = 206) (P < 0.001). Mean clinically significant asthma exacerbation rates were 2.86 and 1.12 per patient-year, respectively (P < 0.001). Omalizumab-treated patients (41.4%) required rescue medication <1 day/week compared with 20.7% for BSC alone (P < 0.001). Omalizumab improved absolute forced expiratory volume in 1 s (FEV(1)) compared with BSC alone (2.48 and 2.28 l, respectively; P < 0.05) and reduced symptom scores relative to BSC alone (decrease of 6.5 and 0.7 respectively; P < 0.001). Omalizumab was well-tolerated.. Omalizumab administered as add-on therapy to BSC benefits patients with poorly controlled, moderate-to-severe allergic asthma.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Leukotriene Antagonists; Male; Middle Aged; Omalizumab; Severity of Illness Index; Survival Analysis; Time Factors; Treatment Outcome

Asthma and allergic rhinitis (AR) form a well-recognized comorbidity. This study aims at assessing the efficacy of nasally inhaled beclomethasone dipropionate (BDP) in their simultaneous treatment. A randomized controlled trial was conducted with 78 allergic rhinitis and asthma patients aged 5-17 years. Seventy-five individuals completed the study. During 8 weeks, 38 subjects received BDP-CFC aerosol (>or= 500 mcg/day) exclusively via nasal inhalation through a facemask attached to a plastic valved spacer. The control group (37 patients) received 200 mcg/day of aqueous intranasal beclomethasone plus oral inhalation of BDP-CFC (>or= 500 mcg/day) through a mouthpiece connected to the same spacer. Primary outcomes analyzed in order to assess the response to treatment were clinical scoring for allergic rhinitis and measurements of nasal inspiratory peak flow (NIPF). AR clinical scoring and NIPF did not differ in the two groups at admission or at nearly all follow-up visits. Nasal inhalation of beclomethasone dipropionate provides AR symptom relief while maintaining control of asthma by delivering it to the lungs. Therefore, this therapeutic strategy might be considered for patients suffering from this comorbidity, especially in low-resource countries, since it is less expensive than the conventional treatment.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Comorbidity; Female; Humans; Male; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Treatment Outcome

A multicenter, randomized, open-label, crossover study with two 4-week evaluation periods compared patient preference and ease of teaching correct inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers (pMDIs). Patients 18 to 65 years of age with stable, mild to moderate asthma, who required or were eligible for inhaled corticosteroid therapy, were randomized to treatment sequences consisting of 4-week evaluation periods with Pulmicort Turbuhaler (budesonide inhalation powder) two puffs (400 microg) bid and one of three inhaled corticosteroids via pMDI: Aerobid-M (flunisolide) four puffs (1 mg) bid, Flovent (fluticasone propionate) two puffs (440 microg) bid, or Vanceril Double Strength (beclomethasone dipropionate) five puffs (420 microg) bid. Patients indicated device preference at study end and completed the Patient Device Experience Assessment (PDEA) questionnaire after each evaluation period. Ease of teaching, time required to master use of the device, percentage of patients demonstrating mastery on the first attempt, and the number of attempts required to demonstrate mastery were assessed. Despite previous use of pMDIs by most patients, Pulmicort Turbuhaler was significantly preferred (p < 0.001) and required significantly less time to master than pMDIs (p < 0.001). Median times to device mastery were 3.67 min for Pulmicort Turbuhaler versus 5.33 min for pMDIs. Patients rated Pulmicort Turbuhaler significantly better than pMDIs on PDEA ease of use (p = 0.0005) and overall satisfaction (p < 0.0001) single-item scales and all four multi-item scales (pharyngeal symptoms, oral sensation, operational use, and inhaler attributes; p < 0.05). Overall, patients preferred Pulmicort Turbuhaler over pMDIs and required less time to be taught how to correctly use Turbuhaler trade mark.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Female; Follow-Up Studies; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Patient Education as Topic; Patient Satisfaction; Probability; Statistics, Nonparametric; Treatment Outcome

The effects of high-dose fluticasone propionate therapy on dynamic cortisol stimulation in severe asthma are unknown.. To evaluate the human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response to fluticasone propionate therapy in severe asthmatic patients with impaired airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted) and in control subjects.. Ten severe asthmatic patients (mean FEV1, 47% of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma cortisol levels before and after hCRF stimulation and overnight 10-hour urinary cortisol excretion corrected for creatinine concentration (OUCC) were measured at baseline after washout and 12 hours after the last dose of fluticasone propionate.. Baseline values before fluticasone propionate use were not significantly different in asthmatic patients vs controls for plasma cortisol before and after hCRF stimulation and OUCC. Comparing values at baseline vs after fluticasone propionate use, there was no significant suppression of plasma cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L) hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In controls, all outcomes were significantly suppressed comparing values before vs after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs 200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002).. Patients with severe persistent asthma and impaired airway caliber seem to be protected from developing systemic adverse effects with high-dose fluticasone propionate therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Breath Tests; Creatinine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eosinophil Granule Proteins; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metered Dose Inhalers; Nitric Oxide; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Ribonucleases; Salmeterol Xinafoate; Theophylline

The study compared clinical efficacy and safety of beclomethasone dipropionate (BDP) given at a dose of 400microg in the mornings and evenings and delivered via pressurised metered dose inhaler (pMDI) with budesonide given via a dry-powder, inspiratory flow driven device at a daily dose of 400microg in the evening. The study was conducted as a week screening. 8-week open comparative clinical trial. At the commencement of the therapy, the baseline characteristics of the patients randomised into the two drug groups were comparable. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEF and FEV1) while safety was assessed by adverse event experiences. At the end of the study, 24 patients (12 in each group) were evaluated. Both drugs were effective in reducing asthma symptoms and frequency of beta2-agonist usage, as well as improving the lung function tests (FEV1 and PEF). However, budesonide given via Turbuhaler provided better effects in all parameters. The drugs were well tolerated and no adverse event was noticed in any of the patients. We therefore concluded that budesonide Turbuhaler administered once daily at a dose of 400microg is more efficacious than beclomethasone 400microg twice daily administered via pressurized metered dose inhaler.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Single-Blind Method; Treatment Outcome

The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6-week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days). A total of 730 adult patients with asthma, age 15-65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50-85% of predicted and > or = 15% improvement in FEV1 after inhaled beta-agonist were enrolled. After a 2-week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 microg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions. The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (+/-SD) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0+/-35.8, montelukast 50.7+/-37.1, beclomethasone 57.9+/-36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (+/-SD) from baseline in FEV1 was 12.1+/-18.7 and 13.9+/-20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4+/-20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences. A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6-week treatment period.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Quinolines; Spirometry; Sulfides; Time Factors

The objective of this double-blind, randomized, placebo-controlled, parallel-group study was to compare the pharmacodynamic effects and safety of beclometasone dipropionate (BDP) given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 1-week run-in period, 40 patients, aged 18-60 years, with intermittent bronchial asthma were randomized to one of four treatment groups for 3 weeks (n = 10 in each group): beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. via a nebulizer, BDP suspension for nebulization 3,200 microg day(-1) b.i.d. via a nebulizer, BDP 800 microg day(-1) b.i.d. via a metered-dose inhaler (MDI) plus spacer, or placebo. At study end, comparable effects were reported for all active treatment groups on the primary pharmacodynamic endpoint of FEV1 in response to methacholine bronchial provocation testing, with a statistically significant improvement shown in the BDP 3,200 microg day(-1) suspension for nebulization group compared with pre-treatment for other parameters, including FEV1 and peak expiratory flow rates. All treatments were comparable. All treatments were equally well tolerated. No significant effects on cortisol levels were reported in any of the treatment groups.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate

Nebulization simplifies the administration of effective inhaled medications to young asthmatics who experience hand-to-lung co-ordination problems and inspiratory difficulties associated with metered-dose and dry-powder inhalers, respectively. The objective of this double-blind, double-dummy multicentre, randomized, parallel-group study was to compare the efficacy and safety of corticosteroids given by nebulization or metered-dose inhalation in paediatric patients with exacerbation of asthma. Following a 24-h run-in period, 151 patients, aged 6-16years, with moderate to severe exacerbation of asthma were randomized to one of two treatment groups for 4 weeks: beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. given via a nebulizer (n = 75), or BDP spray 800 microg day(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 76). Superimposable and statistically significant improvements over baseline were noted at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, asthma symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was the morning pulmonary expiratory flow rate (PEFR). In the BDP nebulization group, mean morning PEFR increased statistically significantly from 233.2 +/- 86.31 min(-1) to 322.0 +/- 101.81 min(-1), while in the BDP MDI group the increase was from 222.9 +/- 87.31 min(-1) to 314.9 +/- 96.61 min(-1). Moreover, an additional 4-week treatment period at half doses, completed by 26 patients, demonstrated that improvements were maintained or further enhanced. The two treatments were equally well tolerated. A total of 25 and 26 patients in the BDP nebulization and BDP MDI groups, respectively reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 1,600 microg day(-1) given via a nebulizer and BDP spray 800 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in paediatric patients with moderate to severe asthma exacerbation.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Patient Satisfaction

Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18-70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3,000-4,000 microgday(-1) b.i.d. given via a nebulizer (n = 63), or BDP spray 1,500-2000 microgday(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 +/- 107.81 min(-1) to 3 19.2 +/- 104.01 min(-1) while in the BDP MDI group the increase was from 301.5 +/- 94.71 min(-1) to 309.3 +/- 86.71 min(-1). The two treatments were equally well tolerated.A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,000-4,000 microg day(-1) given via a nebulizer and BDP spray 1,500-2,000 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Peak Expiratory Flow Rate; Vital Capacity

Inhaled steroids are recommended for long-term control of asthma, but their use may be limited in young children because of difficulties in using the associated inhaler device. The use of nebulizers may help to overcome this issue, without compromising therapeutic efficacy or safety. This 14-week, multicentre, randomized, controlled, open-label, parallel-group study compared the efficacy and safety of nebulized corticosteroids in paediatric patients (aged 6 months to 6 years) with severe persistent asthma. Beclometasone dipropionate (BDP) 800 microgday(-1) suspension for nebulization and budesonide (BUD) 750 microg day(-1) given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters. The primary efficacy endpoint was the number of patients who did not experience any major exacerbation, this being 40.4% and 51.7% in the BDP and BUD groups respectively in the ITT population (P = 0.28), and the mean number of global exacerbations (major plus minor) decreased respectively by -37.5% in the BDP group and -23.3% in the BUD group. Both treatments were also associated with marked reductions in the number of nights with wheezing and the number of days of oral steroid use. Moreover, the two treatment groups had a similar adverse-event incidence and profile. Only 11 adverse events were reported, and no serious adverse events were related to treatment. Urinary cortisol and the time course of height and weight were unaffected by both treatments, and BDP was confirmed to have a neutral effect on bone metabolism. In conclusion, this study demonstrates that both BDP 800 microg day(-1) suspension for nebulization and BUD 750 microgday(-1) administered by nebulization are effective, with an acceptable safety profile, for treatment of severe persistent asthma in infants and young children.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Treatment Outcome

The use of nebulization for the administration of inhaled steroids plays an important role in asthma patients who are unable to use pressurized aerosol or dry-powder inhalers effectively. Moreover, the type of nebulizer used may affect how much drug is delivered to the lungs. The objective of this multinational, multicentre, randomized, active-controlled, parallel-group study was to compare the efficacy and safety of nebulized corticosteroids in adult patients with chronic asthma. Following a 1-week placebo run-in period, 205 patients, aged 18-65 years, with moderate persistent asthma were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 2,400 microg day(-1) b.i.d. (n = 103), or fluticasone propionate (FP) suspension for nebulization 2,000 microg day(-1) b.i.d. (n = 102), both administered by a jet nebulizer Comparable efficacy in controlling asthma was demonstrated by the two treatments at study end, as evident when evaluating various efficacy parameters (pulmonary function tests, asthma exacerbations and symptoms, and the use of rescue salbutamol). The primary efficacy endpoint was the variation in the pulmonary expiratory flow (PEF) at treatment end over the baseline visit. For the intent-to-treat population, in the BDP group mean PEF values increased statistically significantly from 5.2 +/- 1.31 s(-1) to 5.7 +/- 1.61 s(-1), while in the FP group the increase was from 5.2 +/- 1.21 s(-1) to 5.8 +/- 1.81 s(-1). Mean PEF values as per cent of predicted also increased in a statistically significant way, from 71% to 77.1 % in the BDP group, and from 70.1% to 76.9% in the FP group. The two treatments were equally well tolerated.A total of 23 and 32 patients in the BDP and FP groups, respectively, reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP 2,400 microg day(-1) and FP 2,000 microg day(-1), both suspensions for nebulization administered via a jet nebulizer, are equally effective, with an acceptable safety and tolerability profile, when used in adult patients with moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Vital Capacity

To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program.. Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were randomly assigned to control and intervention groups. Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program. Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking. Pediatric Asthma Care Knowledge Survey, Pediatric Asthma Caregiver's Quality of Life Questionnaire, asthma symptom history, spirometry, and health services utilization data were collected at the initial visit and at 3 and 12 months.. Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers, decreased asthma symptom days (81 vs 51 per year), and decreased number of emergency department visits (1.93 vs 0.62 per year) among the intervention group participants. The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids (434 vs 754 micro g [beclomethasone equivalents]) at visit 3. Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits (r = 0.37) and less frequent use of quick-relief medicines (r = 0.30).. Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Caregivers; Child; Computer-Assisted Instruction; Emergency Service, Hospital; Female; Glucocorticoids; Health Education; Humans; Internet; Male; Multimedia; Outcome Assessment, Health Care; Patient Education as Topic; Program Evaluation; Quality of Life; Self Care

Acute severe exacerbation of asthma is potentially life threatening and requires critical assessment and appropriate therapy. Now a days, steroids are often combined with bronchodilators for the treatment of bronchial asthma. Therefore, the present study was undertaken to compare effectiveness of beclomethasone diproprionate-salbutamol combination versus salbutamol alone by MDI (with or without spacer) in acute asthma.. A total of 57 paediatric patients (5-12 years) with acute attack of bronchial asthma attending emergency department of Indira Gandhi Medical College and Hospital was randomised to receive salbutamol (100 microg/puff) alone or with BDP (50 microg/puff) by metered dose inhaler with or without spacer. All baseline investigations were repeated one hour after the therapy.. Clinical parameters indicative of severity of asthma improved statistically in all treatment groups. The increase in PEFR was better with MDI-S+B with spacer as compared to other groups, though it failed to reach statistical significance. The fall in serum potassium level is significantly more with MDI-S+B group when spacer was not used. No serious adverse effects were observed in any of the treatment groups.. Metered dose inhalation of BDP-salbutamol combination with spacer provides better recovery whereas fall in serum potassium with MDI-S+B suggests use of spacer and monitoring of serum potassium during treatment.

Topics: Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Female; Humans; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate

We examined whether a combination of glucocorticoids and beta-agonists inhaled by asthmatics had an influence on the metabolism of L-arginine, an amino acid involved in the production of urea, creatinine, and NO that is known to play a significant role in asthma. After lung function tests, we assayed nitrates, urea, and creatinine and determined urinary osmolality in urine samples taken from groups of 129 children (10+/-3 years old) with mild-to-moderate asthma treated with different regimens of drugs. No significant differences in urinary urea levels were noted between the groups. On the other hand, the children treated by the combination of glucocorticoid and beta-agonist (n = 52) had a higher level of urinary creatinine (+40%, P < .001, and a higher creatinine/urea ratio (C/U) expressed as % mass= 5.98 +/- 2.44, P < .001) than did the untreated children (n = 43, C/U = 4.03 +/- 1.24), those treated with glucocorticoid (n = 23, C/U = 4.01 +/- 1.32) or beta-agonist alone (n = 11, C/U = 4.09 +/- 1.01) or control children of the same age (n = 20, C/U = 4.81 +/- .90). Children treated with beta-agonist alone had the lowest mean levels of urinary nitrates (P < .05). The children in group 1 whose C/U ratio was above 6 (n = 24) had a higher FVC (P < .02) and FEV1 (not significant (NS)). However, an overly high C/U may also be indicative of a deleterious influence on the biosynthesis of NO from arginine. Further investigations will be required to determine whether there is a relationship between C/U ratios and lung function parameters, and whether the urinary C/U ratio could be employed as a simple and noninvasive parameter for assessment of treatment in asthmatics.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Creatinine; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Nitrates; Osmolar Concentration; Salmeterol Xinafoate; Terbutaline; Urea

To determine whether the dose of inhaled corticosteroids can be stepped down in patients with chronic stable asthma while maintaining control.. One year, randomised controlled, double blind, parallel group trial.. General practices throughout western and central Scotland.. 259 adult patients with asthma receiving regular treatment with inhaled corticosteroids at high dose (mean dose 1430 microg beclomethasone dipropionate).. Participants were allocated to receive either no alteration to their dose of inhaled corticosteroid (control) or a 50% reduction in their dose if they met criteria for stable asthma (stepdown).. Comparison of asthma exacerbation rates, asthma related visits to general practice and hospital, health status measures, and corticosteroid dosage between the two groups.. The proportions of subjects with asthma exacerbations were not significantly different (stepdown 31%, control 26%, P=0.354). Similarly, the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different. On average the stepdown group received 348 microg (95% confidence interval 202 microg to 494 microg) of beclomethasone dipropionate less per day than the controls (a difference of 25%), with no difference in the annual dose of oral corticosteroids between the two treatment regimens.. By adopting a stepdown approach to the use of inhaled steroids at high doses in asthma a reduction in the dose can be achieved without compromising asthma control.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Health Status; Humans; Middle Aged; Treatment Outcome

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Budesonide; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Middle Aged; Reference Values; Regional Blood Flow; Severity of Illness Index; Vasoconstriction

QVAR, an extrafine hydrofluoroalkane/beclomethasone dipropionate formulation, has been shown to double lung deposition in adults. The aim of the present study was to assess the total body deposition and distribution of technetium-99m-labelled (99mTc) QVAR in children after inhalation via an Autohaler. Sixteen male asthmatic children (5-14 yrs) inhaled labelled drug (<4 MBq 99mTc; 100 microg beclomethasone dipropionate) via an Autohaler within 30 min after salbutamol (200 microg) administration. Simultaneous anterior and posterior planar scintigraphic scans (120 s acquisition time) were collected after inhalation of labelled drug. Mean+/-SD lung deposition of labelled drug (attenuation-corrected; percentage of ex-actuator dose) was 36.9+/-9.2, 46.5+/-11.6 and 54.1+/-10.7% in children aged 5-7, 8-10 and 11-14 yrs, respectively. Combined oropharyngeal and gastrointestinal deposition was 59.7+/-8.2, 48.9+/-12.3 and 40.3+/-11.8%. Lung deposition positively correlated with the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Gastrointestinal dose negatively correlated with the FEV1, FVC, height and age. In older children (11-14 yrs), lung deposition was almost identical to that reported in adults using QVAR. In children aged 5-10 yrs, lung deposition using QVAR was greater than the levels measured using other commercial aerosol delivery systems. Oropharygeal and gastrointestinal deposition was inversely related to age.

Topics: Administration, Inhalation; Adolescent; Age Factors; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Humans; Hydrocarbons, Fluorinated; In Vitro Techniques; Male; Metered Dose Inhalers; Radionuclide Imaging; Reproducibility of Results; Severity of Illness Index; Technetium

To evaluate the therapeutic effects of H(1) blocker in combination with low dose inhaled corticosteroid on allergic asthma.. A multi-center, double blind, randomized, placebo control study was conducted in 67 patients with mild to moderate allergic asthma. Patients were randomized to receive either Loratadine 10 mg or placebo twice a day on the basis of inhaled beclomethasone dipropionate (400 microg/d for 14 days, then reduced to 200 microg/d) for 5.3 +/- 1.3 months. Symptom scores of asthma, frequencies of episode of rhinitis and common cold and doses of inhaled Salbutamol as rescue drug were recorded. Bronchial hyperresponsiveness (PD(20) FEV(1) in response to Histamine) and serum ICAM-1 and VCAM-1 were measured before and after the treatment.. After treatment, there was much better improvement in symptom score (2.4 +/- 0.9 vs 3.1 +/- 0.9, P < 0.01), symptomatic days due to rhinitis (4.0 +/- 1.2 d/week vs 1.9 +/- 0.9 d/week, P < 0.001), episode of common cold symptom (0.8 +/- 0.5 time vs 1.1 +/- 0.4 time, P < 0.001), average doses of inhaled beta(2) agonist as rescue medication (2.6 +/- 0.9 puff/week vs 3.7 +/- 0.8 puff/week, P < 0.001) and bronchial responsiveness (P < 0.05) in Loratadine group as compared with the control group. However, there was no significant change in serum ICAM-1 and VCAM-1 levels after treatment in both groups (P > 0.05).. On the basis of low dose inhaled corticosteroid, orally administered Loratadine significantly improves the therapeutic efficacy of asthma in patients with allergic asthma and rhinitis.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Intercellular Adhesion Molecule-1; Loratadine; Male; Middle Aged; Rhinitis, Allergic, Perennial; Vascular Cell Adhesion Molecule-1

Inhaled steroids are the most commonly used anti-inflammatory agents for asthma and are increasingly recognised as having a more rapid onset of action than was previously thought. We have investigated the effect of a single dose of inhaled steroid on nocturnal worsening of asthma.. Ten patients with steroid naive moderate asthma and nocturnal asthma participated in a randomised, double blind, placebo controlled, crossover trial. Participants spent three nights in the laboratory, one week apart. On each night they underwent spirometric testing at 16.00 hours and received one of the three treatments (placebo, beclomethasone 1000 micro g, or fluticasone 1000 micro g) delivered by metered dose inhaler. Spirometric tests were repeated at 04.00 hours the following morning.. Following placebo administration the mean (SE) overnight fall in FEV(1) was 0.65 (0.27) l compared with -0.02 (0.13) l following fluticasone (p=0.019) and 0.23 (0.12) l following beclomethasone (p=0.048 v placebo).. A single dose of inhaled steroid (within the therapeutic range) reduced the fall in FEV(1) in patients with nocturnal asthma when administered at 16.00 hours. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single night study.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged

Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur.. To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis.. The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter.. The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids.. Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Androstadienes; Anti-Inflammatory Agents; Antifungal Agents; Asthma; Beclomethasone; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Fluticasone; Glucocorticoids; Humans; Japan; Male; Middle Aged; Regression Analysis; Statistics as Topic; Treatment Failure

This double-blind, randomised, multi-centre, parallel-group study compared the effect of adding Foradil (formoterol fumarate) to existing medium-high doses of inhaled corticosteroids (ICS) with that of doubling the dose of ICS in patients with sub-optimally controlled asthma. After a run-in period, 203 patients with moderate-to-severe asthma who remained symptomatic despite treatment with 500 microg beclomethasone twice daily, were randomised to receive either 12 microg formoterol twice daily (Foradil Aerolizer), Novartis) in addition to beclomethasone 500 microg twice daily, or beclomethasone 1000 microg twice daily and placebo for 12 weeks. The primary efficacy variable was mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment. The difference in PEF between treatments was 27.78 l/min in favour of the formoterol/beclomethasone combination (95% CI 13.42, 42.14 l/min, p=0.0002, intention-to-treat population). Significant differences in the urinary cortisol/creatinine ratio between treatment groups at 12 weeks (p=0.001) indicated suppression of the hypothalamic-pituitary-adrenal axis in the patients on beclomethasone 1000 microg twice daily. The addition of formoterol 12 microg twice daily to beclomethasone in patients with asthma who were poorly controlled with beclomethasone 500 microg twice daily was more effective than doubling the ICS dose and resulted in less suppression of the hypothalamic-pituitary-adrenal axis.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Australia; Beclomethasone; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Humans; Male; Middle Aged

Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD.. HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful.. There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful.. Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Fluticasone; Humans; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome

To evaluate the long-term effects of the anti-IgE antibody omalizumab in children with asthma.. This was a 28-week, double-blind, randomized, placebo-controlled trial with a 24-week open-label extension. In the core trial 225 children (ages 6 to 12 years) with moderate-to-severe allergic asthma requiring inhaled beclomethasone dipropionate (BDP) received omalizumab every 2 or 4 weeks, and 109 received placebo. BDP dosage was stable for weeks 1 to 16, then reduced during weeks 17 to 24 using strict safety criteria. The lowest dose for optimal asthma control was maintained for 4 more weeks. During the 24-week extension, all patients (n = 309) received open-label omalizumab in addition to other asthma medications. One-year safety data were analyzed.. The incidence of adverse events in patients treated with omalizumab for 52 weeks was similar to those treated for 28 weeks in the core trial, which was generally comparable with placebo. In the 52-week omalizumab group, upper respiratory tract infection and headache were the most frequently reported adverse events (47.1% and 42.7%, respectively). Eleven patients (4.9%) reported urticaria, which resolved spontaneously or with antihistamine, except for 1 patient who was discontinued because of severe urticaria. No anaphylactic reactions or adverse events suggestive of serum sickness or immune complex formation occurred. No anti-omalizumab antibodies were detected in any of the children. There is no evidence that new or more serious adverse events occur with long-term omalizumab treatment.. Long-term treatment with omalizumab is safe and well tolerated in children with allergic asthma.

Topics: Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Injections, Subcutaneous; Longitudinal Studies; Male; Omalizumab; Platelet Count

The aim of the present study was to assess the dose-dependency from inhaled steroids of changes of airways inflammation [eosinophils count and eosinophil cationic protein (ECP)] measures in induced sputum and in serum, as well as that of exhaled nitric oxide. Twenty steroid-naive patients with nonatopic asthma of mild to moderate degree [forced expiratory volume in 1 s (FEV1) = 70% of predicted] and with negative response to the standard tests for allergy were selected; after a 1-week run-in period they were randomized to receive a 12-week treatment period of inhaled beclomethasone dipropionate dry powder given with the Pulvinal inhaler (Clenil P, Chiesi Farmaceutici S.p.A., Parma, Italy) in two different dose regimens, 400 microg bid (high dose) or 200 microg bid (low dose), over a double blind, parallel groups design. The following outcome measures were assessed in baseline and after 1, 6 and 12 weeks of treatment: FEV1 (l), eosinophils count in sputum (%), is ECP (microg/l), serum eosinophils count (%), serum ECP (microg/l) and exhaled NO (ppb). The results showed that all the considered parameters improved in both groups: the increase over baseline of FEV1 and the decrease of NO were significant at any time in the high-dose group and only at week 12 in the low-dose group (NS between groups), whereas the markers of eosinophilic activity showed more consistent reductions in the high-dose than in the low-dose group when measured in induced sputum (P < 0.05 between groups after 6 and 12 weeks for eosinophils count and after 12 weeks for ECP). Decreases over baseline of markers measured in serum were more rapid in the high-dose group, without differences between groups. A marked trend towards a negative correlation was found between FEV1 and ECP, (r = -0.72, P < 0.05), between FEV1 and eosinophils in sputum (r = -0.31, NS) and between FEV1 and exhaled NO (r = -0.38, NS), all of them only in the high-dose group. The results of the study demonstrate that changes of levels of eosinophilic activity in the airways are dependent from the daily dose of inhaled steroids when measured in induced sputum and that the local assessment can therefore represent a practical and noninvasive method to monitor the extent of airways inflammation.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Dose-Response Relationship, Drug; Eosinophil Granule Proteins; Eosinophils; Exhalation; Female; Humans; Male; Middle Aged; Nitric Oxide; Pulmonary Eosinophilia; Ribonucleases; Sputum

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 microg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33-77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200-900 microg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200-600 microg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6-7.9 microg/dL, p < 0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p < 0.01; evening: 67.3 to 72.1%, both p < 0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p < 0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.

Topics: Administration, Inhalation; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal Function Tests

Eighty-one adult patients with bronchial asthma who suffered asthmatic episodes in spite of treatment with 400 mg/day of BDP were placed on pranlukast therapy for 4 weeks. Group I, which showed a 5% or greater increase in PEFR, continued oral pranlukast medication for an additional two years. Those patients who did not show an increase of 5% or greater in PEFR after 4 weeks of pranlukast therapy were instructed to continue the medication for another year. Group II, which exhibited a 5% or greater increase in PEFR after a one-year period continued medication for one more year. Medication was suspended for Group III, which failed to show improvement in PEFR after one year, and the group was placed under observation for the following year. Group I improved significantly in PEFR and exhibited a reduction in the frequency of b2 inhalation, the number of night visits to a medical facility, the amount of steroids inhaled, and the quantity of oral steroids given at regular intervals; and the Group I peripheral eosinophil count, serum ECP level, and FEV1.0 ameliorated. After one year, Group II also showed significant improvement in PEFR and a reduction in both the peripheral eosinophil count and the serum ECP level. This group's PEFR continued to improve after two years. One year after medication was suspended, Group III showed a significant increase in the number of night visits to a medical facility and a rise in the serum ECP level. These findings indicated the efficacy of pranlukast.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Chromones; Drug Therapy, Combination; Eosinophil Granule Proteins; Eosinophils; Female; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Ribonucleases; Treatment Outcome

Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance.. Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days.. The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide.. Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Humans; Ipratropium; Middle Aged; Mucociliary Clearance; Placebos; Radionuclide Imaging

This study investigated the impact of providing low-dose inhaled corticosteroids (ICS) at school or at home to asthmatic inner city children over a 14-week period, compared with the existing community standard. Eight elementary schools in the Dallas Independent School District with a high incidence of asthma located in predominantly urban African-American communities were randomly assigned to one of four groups. The treatment arms were school-based delivery of inhaled steroids, home-based delivery of inhaled steroids, and home-based delivery of inhaled steroids with school-based asthma education, and the control group was no change in current therapy. Fifty students were objectively diagnosed with mild, persistent asthma and participated in the study. Students in the treatment arms received beclomethasone (42 mcg/puff) 4 puffs, twice a day, either at school or at home. Students in the control, "community standard of care" group received no additional medical intervention. Higher peak flows for the treatment groups were seen in the first week and maintained throughout the study (P = .047). By week 5 significant differences were found in frequency of bronchodilator use (P = .025), episodes of nocturnal awakening with asthma symptoms (P = .022), and visits to the primary health care provider (P = .022). Treatment groups rated their asthma as "better than the week before" more frequently than the control group (P = .001). Delivering ICS in school is associated with improved asthma control than when anti-inflammatory medication was delivered to children with asthma in a home-based setting, and both are superior when compared with a control, "community standard of care" group in which no additional medical intervention occurred.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Glucocorticoids; Humans; Patient Education as Topic; School Health Services; Urban Health

Inhaled corticosteroids for asthma treatment have become mainstay of therapy for patients with persistent asthma. Numerous inhaled corticosteroids are available but to date no prospective cost-effectiveness studies have been reported using exclusively US patients and costs. The purpose of this study was to examine the cost-effectiveness of HFA-bectomethasone (QVAR) compared to CFC-beclomethasone (Vanceril) using data from a year-long prospective randomized, open label, parallel multicenter trial. Eligibility criteria required patients to have been on a stable dose of CFC-BDP prior to enrollment. Patients were randomized to either HFA-BDP at approximately half their previous daily dose of CFC-BDP or to continue CFC-BDP Effectiveness data, in terms of symptom-free days (SFDs), were used in a cost-effectiveness analysis conducted from the viewpoint of managed care. Patients receiving HFA-BDP reported a greater increase (median = 22.1) in the number of SFDs than those receiving CFC-BDP (median = 14.3) (P = 0.03). Total costs of care were less for patients taking HFA-BDP (median = dollars 668) compared to CFC-BDP (median = dollars 977). The median incremental cost-effectiveness ratio was dollars -5.77 (95% CI: dollars -68.08 to dollars -4.08). The results of this analysis indicate that HFA-BDP was a dominant therapy (more effective, less costly) compared to CFC-BDP.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Cost-Benefit Analysis; Drug Costs; Female; Forced Expiratory Volume; Health Resources; Humans; Hydrocarbons, Fluorinated; Male

Th2 cytokines play an important role in the pathogenesis of asthma. In the present study, we investigated the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control, in terms of subjective symptoms and pulmonary function in patients treated with inhaled corticosteroids. Thirty-eight patients with bronchial asthma being treated with inhaled corticosteroids were given suplatast tosilate (100 mg three times daily) for 12 weeks, in a multicenter setting. During the study period, other medications were continued. Morning and evening peak expiratory flow, asthma symptoms, blood eosinophil count and serum IgE levels were monitored. Suplatast tosilate treatment was associated with a significant improvement in mean morning peak expiratory flow (from 295 L/min to 348 L/min, P < 0.01) and evening peak expiratory flow (from 313 L/min to 357 L/min, P < 0.01). The mean daily variation in peak expiratory flow was significantly reduced (from 11.6% to 7.3%, P < 0.01) by suplatast tosilate treatment. The greatest improvement in peak expiratory flow was observed in patients whose blood eosinophil counts were decreased by suplatast tosilate treatment. Treatment with suplatast tosilate improved pulmonary function in patients with bronchial asthma. Our results suggest the therapeutic effects observed may occur through suppression of eosinophilic inflammation.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Arylsulfonates; Asthma; Beclomethasone; Cytokines; Histamine Antagonists; Humans; Peak Expiratory Flow Rate; Sulfonium Compounds; Th2 Cells

It is now recommended to add an inhaled long-acting beta 2-agonist, or as an alternative, to add a leukotriene-antagonist, in patients whose asthma is insufficiently controlled with an inhaled corticosteroid alone. A randomised, multicentre, open-label, parallel-group study was carried out in 246 patients of at least 15 years, whose asthma was not adequately controlled with a medium dose of an inhaled corticosteroid. They received either fluticasone/salmeterol combination 250/50 micrograms one inhalation twice daily or CFC beclomethasone dipropionate 250 micrograms two puffs twice daily plus montelukast 10 mg in the evening for 12 weeks. The mean morning PEFR (main criterion) was significantly (p = 0.017) more improved with fluticasone/salmeterol (+44.2 L/min) than with beclomethasone dipropionate plus montelukast (+31.0 L/min). Other outcomes showed significantly better improvements (p 0.022 Pound) with fluticasone/salmeterol than with beclomethasone plus montelukast. The two treatments were well tolerated. Fluticasone/salmeterol provided a better asthma control than beclomethasone dipropionate plus montelukast in patients insufficiently controlled with an inhaled corticosteroid alone.

Topics: Acetates; Administration, Inhalation; Adult; Aerosols; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cyclopropanes; Drug Combinations; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Powders; Prospective Studies; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

To examine the relationship between changes in quality of life and measures of lung function and bronchial hyper-responsiveness (BHR) during treatment with high-dose inhaled corticosteroids in patients with uncontrolled asthma.. Thirty patients with uncontrolled asthma currently receiving inhaled corticosteroids (median dose 550 microg/day) were treated with beclomethasone dipropionate (BDP) dry powder 2000 microg/day for 4 weeks. Patients completed the Asthma Quality of Life Questionnaire (AQLQ), underwent bronchial challenge with methacholine and spirometry, and made entries in asthma diary cards at baseline and after treatment with beclomethasone dipropionate.. The mean change in overall AQLQ score improved significantly (p < 0.05) during the 4-week period by 0.57 (95% CI 0.29-0.84, p < 0.05), representing a minimal important difference, with similar improvements in individual domains. Change in overall AQLQ score correlated significantly with FEV(1) (p < 0.001), forced mid-expiratory flow between 25-75% of vital capacity (FEF(25-75)) [p < 0.05] and morning PEF (p < 0.05), but not with methacholine PD(20) i.e. the provocative dose of methacholine causing a 20% fall in FEV(1).. Quality-of-life scores related to changes in lung function but not BHR during short-term high-dose inhaled corticosteroid therapy for uncontrolled asthma.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Lung; Middle Aged; Quality of Life; Respiratory Function Tests

To assess the impact of the Buteyko Breathing Technique (BBT) on medication use in asthma.. A blinded randomised controlled trial comparing BBT with control was conducted in 38 people with asthma aged between 18 and 70. Participants were followed for six months following the intervention. Medication use and indices of ventilatory function were recorded.. No significant change in FEV1 (forced expiratory volume in one second) was recorded in either group. The BBT group exhibited a reduction in inhaled steroid use of 50% and beta2-agonist use of 85% at six months from baseline. In the control group inhaled steroid use was unchanged and beta2-agonist use was reduced by 37% from baseline. Investigator contact between the two groups was equal. There were no adverse events recorded in either group.. BBT is a safe and efficacious asthma management technique. BBT has clinical and potential pharmaco-economic benefits that merit further study.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Asthma; Beclomethasone; Combined Modality Therapy; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Respiratory Therapy; Single-Blind Method

Activated eosinophils play a critical role in asthma pathogenesis, and eosinophil cationic protein (ECP) is a useful indicator of inflammation. Inhaled corticosteroids and long-acting beta2-agonists (LABA) effectively control asthma symptoms and improve airway function. Salmeterol's anti-inflammatory efficacy as add-on therapy to inhaled corticosteroids has not been evaluated in Caribbean populations. We investigated nine non-smoking subjects (three men and six women; mean age: +/- SE, 50.7 +/- 3.82 years) with stable mild and moderate persistent asthma who were inhaling > or = 500 microg beclomethasone dipropionate (BDP) daily. This was a with-in-patient controlled laboratory blind study performed over 8 weeks. Patients received BDP for 2 weeks, add-on salmeterol 100 microg in weeks 3-6 and BDP alone in weeks 7-8. Patients recorded daily morning and night symptoms. Morning peak expiratory flow rate was measured on entry to the study and with sputum ECP at the end of weeks 2, 4, 6 and 8. Salmeterol together with BDP decreased sputum ECP from a pretreatment median value of 897.84 microg/l to 628.38 microg/l after 4 weeks, and ECP continued to decrease even after salmeterol withdrawal. Both drugs decreased the frequency of rescue medication use by approximately 50% and increased the median number of days per week without rescue salbutamol from 0 to 3 days. Salmeterol's bronchoprotective effect was maximal after 4 weeks and was sustained after its withdrawal. In conclusion, this study, performed in Trinidadian asthmatics, used ECP as a surrogate marker of bronchial inflammation and supports the recent Salmeterol Multi-center Asthma Research Trial (SMART) data recommending add-on salmeterol therapy to adequate anti-inflammatory medication such as inhaled corticosteroids for optimal asthma management. Further studies are required to evaluate the anti-inflammatory efficacy and possible tolerance to salmeterol in Caribbean patients.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Eosinophil Granule Proteins; Eosinophils; Female; Humans; Male; Middle Aged; Outpatients; Ribonucleases; Salmeterol Xinafoate; Treatment Outcome; Trinidad and Tobago

In adults with asthma, hydrofluoralkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol provides equivalent asthma control at half the daily dose of conventional chlorofluorocarbon (CFC)-BDP.. We sought to compare the efficacy and tolerability of switching from CFC-BDP to HFA-BDP at half the daily dose in children with stable asthma.. This 6-month, open-label, randomized, multicenter study enrolled 520 children aged 5 to 11 years with well-controlled asthma receiving inhaled CFC-BDP or budesonide 200 to 800 microg/d x. (Four hundred fifty-two patients were using doses within the recommended range of 200-400 microg and were analyzed separately.) During a 4-week run-in period, patients used CFC-BDP plus a spacer (CFC-BDP+S) at approximately the same dose as they were using before study entry. Patients were then randomized in a 1:3 ratio to continue on CFC-BDP+S or switch to HFA-BDP Autohaler at half the daily dose.. The change from baseline in morning peak expiratory flow was significantly greater in patients receiving 100-200 microg of HFA-BDP compared with those receiving 200-400 microg of CFC-BDP+S at weeks 7 to 8 (8.5 and 0.4 L/min, respectively; P =.014), with continuing improvement in both groups over 6 months (12.2 and 12.4 L/min, respectively, at month 6). There were no significant differences between treatments in mean change from baseline in FEV(1), percentage of days or nights without asthma symptoms, and daily beta-agonist use over the 6-month treatment period. The proportion of patients who had one or more asthma exacerbations, the incidence of adverse events, and the percentage change from baseline in 24-hour urinary free cortisol levels were similar in the 2 treatment groups.. This study confirms that asthma control can be well maintained in children when switching from CFC-BDP+S to an HFA-BDP Autohaler at doses as low as 100 to 200 microg/d.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Chlorofluorocarbons; Drug Administration Schedule; Female; Humans; Hydrocarbons, Fluorinated; Male; Patient Compliance; Treatment Outcome

To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate (BDP) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable.. Twenty-four patients with mild-to-moderate asthma were studied using a randomized crossover design with the following three treatment blocks: (1) beclomethasone, 100 microg/d, alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks; (2) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of zafirlukast, 20 mg bid; (3) beclomethasone, 100 microg/d, followed by 400 microg/d, with the addition of theophylline, 200 to 300 mg bid. Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline.. The mean trough plasma theophylline concentration was 6.7 mg/L, coinciding with the anti-inflammatory target range (ie, 5 to 10 mg/L). The provocative dose of methacholine causing a 20% fall in FEV(1) (as doubling dose difference from baseline) was significantly (p < 0.05) greater with beclomethasone, 100 microg, plus zafirlukast (1.1 doubling dose) but not with beclomethasone, 100 microg, plus theophylline (0.7 doubling dose) compared to beclomethasone, 100 microg alone (0.4 doubling dose), but not compared to beclomethasone, 400 microg alone (1.1 doubling dose). There were also significant (p < 0.05) differences between beclomethasone, 100 microg, plus zafirlukast (but not BDP, 100 microg, plus theophylline) vs beclomethasone, 100 microg, alone in terms of nitric oxide level, midexpiratory phase of forced expiratory flow, and peak expiratory flow. There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone, 400 microg.. A leukotriene receptor antagonist, but not low-dose theophylline, conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid. Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Respiratory Function Tests; Sulfonamides; Theophylline; Tosyl Compounds

Steroid-induced adverse effects including suppression of humoral immunity should be considered in steroid-dependent severe asthma. Only a few studies have determined the exact steroid dose that could potentially suppress humoral immunity in asthmatics.. Randomly selected 100 adult asthmatics treated with inhaled beclomethasone dipropionate (BDP) were classified into three groups based on the dose of steroid to determine the serum IgG, IgA and IgM levels by radioimmunoassay. Relationships between serum immunoglobulin levels and the daily dose and duration of oral prednisolone (PSL) therapy were examined.. None of the patients on inhaled corticosteroid alone had hypogammaglobulinemia. Patients on oral PSL at a dose >12.5 mg/day for at least 1 year had low serum IgG. There was no significant correlation between the duration of oral PSL therapy and serum IgG.. Oral PSL can potentially suppress humoral immunity in severe asthma. In asthmatics, hypogammaglobulinemia could develop in those on a daily dose of PSL >12.5 mg, but is independent of the duration of such treatment. No suppression of humoral immunity was noted on inhaled corticosteroid therapy alone, either at low or high dose.

Topics: Administration, Inhalation; Administration, Oral; Adult; Agammaglobulinemia; Anti-Inflammatory Agents; Asthma; Beclomethasone; Drug Therapy, Combination; Female; Humans; Immunoglobulins; Male; Middle Aged; Prednisolone; Time Factors

Symptoms often deteriorate in well-controlled asthmatics after a step down in inhaled beclomethasone dipropionate (iBDP) therapy if the serum concentration of eosinophil cationic protein (sECP) is high. This deterioration is significantly abrogated by pranlukast, a leukotriene receptor antagonist, or by seratrodast, a thromboxane A2 receptor antagonist. However, these results were based on short-term (less than 6 months) observations.. We studied 35 well-controlled adult asthmatics. We assigned the patients into different groups according to their sECP levels before the step down: (i) group A, sECP < 25 microg/L; (ii) group B, sECP > or = 25 microg/L; and (iii) group C, sECP > or = 25 microg/L but patients treated with pranlukast or seratrodast. We began the study with a step down in iBDP therapy (initial step down), then followed the clinical course of the asthma for 2 years. During the study period, we decreased, increased or maintained the iBDP dose on the basis of the stepwise approach described in the National Institutes of Health guidelines. We monitored the time and frequency of exacerbation and evaluated the iBDP dose required to control the asthma symptoms.. The rates of exacerbation after the step down were high in groups A and B. In group A, the conditions were again qualified for the step down in all patients, but this was not the case for most group B patients. From 15 to 21 months after the initial step down, the average dose of iBDP required to control symptoms was significantly higher in group B than in group A patients (P = 0.0127-0.0373). The exacerbation rate in group C after 12 months tended to be lower than in the other two patient groups (P = 0.0743). In group C, the average dose of iBDP from 9 to 24 months after the initial step down was significantly lower than before the step down (P < 0.0001) and was not significantly different from the mean dose of iBDP in groups A or B.. High sECP in well-controlled asthma may indicate the necessity for a higher iBDP dose over a long period than when the sECP concentration is not high. Even if sECP is high, pranlukast or seratrodast help to prevent exacerbation of asthma and enable successful step down in iBDP therapy for at least 2 years thereafter.

Topics: Adult; Aged; Analysis of Variance; Asthma; Beclomethasone; Benzoquinones; Blood Proteins; Chromones; Chronic Disease; Drug Therapy, Combination; Eosinophil Granule Proteins; Female; Glucocorticoids; Heptanoic Acids; Humans; Leukotriene Antagonists; Male; Middle Aged; Prognosis; Prospective Studies; Prostaglandin Antagonists; Respiratory Mechanics; Ribonucleases; Statistics, Nonparametric

To compare the cost effectiveness of hydrofluoroalkane 134a-beclomethasone dipropionate (HFA-BDP; Qvar) [corrected] with chlorofluorocarbon-beclomethasone dipropionate (CFC-BDP) in patients with chronic stable asthma previously receiving CFC-BDP, from the perspective of a healthcare provider.. Cost-effectiveness analysis based on a 12-month pragmatic, randomised, parallel group, open-label clinical trial assessing safety and efficacy of HFA-BDP at approximately half the dose of CFC-BDP in patients with stable asthma.. International, multicentre study at 57 study sites in the US, UK, The Netherlands, and Belgium. Healthcare costs were calculated for UK-based healthcare [in 1999 as pounds (pounds sterling)].. Patients (n = 473) > or =12 years of age with currently stable asthma that had been stable (i.e. no exacerbations requiring oral corticosteroid use in the last 4 weeks) for at least the preceding month.. Average and incremental cost-effectiveness ratios based upon symptom-free days, improvement in health-related quality of life, and total and drug-only direct healthcare costs.. Patients in the HFA-BDP group experienced a significantly higher percentage of symptom-free days than patients in the CFC-BDP group by the end of the study period (42.4 vs 20.0%; p = 0.006). A greater percentage of patients in the HFA-BDP group had a clinically significant improvement in health-related quality of life than in the CFC-BDP group [35.3 (n = 116/329) vs 16.1% (n = 18/112)]. Total per patient healthcare costs were similar between the two groups. The average cost per symptom-free day per patient was 1.36 pounds sterling for HFA-BDP and 1.81 pounds sterling for CFC-BDP based on total healthcare costs. The incremental cost per symptom-free day for using HFA-BDP instead of CFC-BDP was negative, indicating that HFA-BDP is a dominant strategy and may be a cost-saving intervention compared with CFC-BDP. A sensitivity analysis varying both cost and outcome parameters further supported this finding for most scenarios tested. The cost to achieve a clinically significant improvement in health-related quality of life over the study period was 13.24 pounds sterling per improved patient per week for HFA-BDP and 29.38 pounds sterling per patient per week for CFC-BDP.. These findings indicate that HFA-BDP is a cost-effective intervention when compared with CFC-BDP in this group of patients with stable asthma. In the majority of scenarios HFA-BDP provides more effective asthma control at a similar cost to CFC-BDP.

Topics: Asthma; Beclomethasone; Chlorofluorocarbons; Chronic Disease; Cost-Benefit Analysis; Humans; Hydrocarbons, Fluorinated; Prospective Studies; Quality of Life; Treatment Outcome

Inhaled corticosteroids and long-acting beta2-agonists effectively control asthma symptoms and improve airway function. The effects of beclomethasone were compared with those of salmeterol on markers of eosinophilic inflammation in induced sputum in steroid-naive asthmatic subjects with moderate asthma. Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 microg b.i.d.) or salmeterol (50 microg b.i.d.) for 4 weeks, according to a randomised, double-blind, parallel-group study design. All patients underwent spirometry, methacholine test, sputum induction, and blood sampling before and after 2 and 4 weeks of treatment. They also recorded daily symptoms and peak expiratory flow (PEF). Sputum eosinophils, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and blood eosinophils, as well as the forced expiratory volume in one second (FEV1) and morning PEF, significantly improved after beclomethasone but not after salmeterol. PEF variability, the symptom score and rescue beta2-agonist use significantly improved after both treatments, although the improvement in the symptom score tended to be greater after beclomethasone. After 2 and 4 weeks of beclomethasone treatment, both serum ECP and EPX decreased. With salmeterol, only serum EPX decreased, after 4 weeks. Bronchial hyperresponsiveness to methacholine did not change after either treatment. The authors conclude that beclomethasone, but not salmeterol, substantially improves airway inflammation in asthma. Beclomethasone also had an overall greater clinical effect, although the improvement in symptoms and peak expiratory flow variability was similar after both treatments.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Proteins; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Humans; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Respiratory Function Tests; Ribonucleases; Salmeterol Xinafoate; Severity of Illness Index; Sputum

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 microg x day(-1)) than in the placebo group (43 microg x day(-1)). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypersensitivity; Male; Middle Aged; Omalizumab; Severity of Illness Index; Time Factors; Treatment Outcome

Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.. After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.. Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).. Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Quality of Life; Survival Analysis; Treatment Outcome

In the drive to replace chlorofluorinated hydrocarbons (CFCs) by alternative more environmentally friendly propellants in pressurized metered dose inhalers (pMDIs), Chiesi has developed new inhalers using Modulite technology. The aim was to obtain CFC-free pMDIs which are equivalent, in terms of safety and efficacy, to the previous CFC devices at the same dose. When beclometasone dipropionate (BDP) and budesonide Modulite formulations were compared to the equivalent CFC products there was no significant difference in morning serum cortisol or urinary cortisol excretion, at the maximum recommended daily dose (2000 micrograms or 1600 micrograms respectively). Single dose pharmacokinetic studies in both healthy volunteers and asthmatic patients compared systemic exposure (B17MP levels) for BDP-CFC with BDP Modulite and extrafine BDP-HFA (QVAR). B17MP levels for BDP-CFC and BDP Modulite were comparable, but substantially less than that seen with extrafine BDP-HFA. After 6 weeks of treatment in asthmatic patients, B17MP AUC after inhalation of BDP (1000 micrograms twice-daily) from BDP Modulite was comparable with that obtained after BDP-CFC (Becloforte). Plasma profile of BDP and B17MP were similar after inhalation from BDP Modulite with standard actuator or delivered via a spacer, suggesting that pulmonary delivery of BDP to the lung is similar with both actuators.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Cross-Over Studies; Double-Blind Method; Drug Delivery Systems; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Nebulizers and Vaporizers; Therapeutic Equivalency

With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.. Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).. For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).. There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoconstrictor Agents; Bronchodilator Agents; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Methacholine Chloride

Exhaled nitric oxide (eNO) is an easily measured marker of airway inflammation. This study was undertaken to evaluate the usefulness of serial eNO in investigating the dose-response relationship for inhaled beclomethasone (BDP), and to compare eNO with other markers of airway inflammation. Following withdrawal of inhaled corticosteroid (ICS) therapy, 65 patients entered a double-blind, parallel-group, placebo-controlled trial of 50, 100, 200 or 500 microg x BDP x day(-1) for eight weeks. eNO and spirometry were performed weekly and a hypertonic saline challenge with sputum induction was performed at the beginning and end of treatment. The relationship between the dose of ICS and changes in eNO and forced expiratory volume in one second (FEV1) was linear at 1 week and at the end of treatment. A linear dose-response relationship was also seen for sputum eosinophils. Changes in eNO correlated significantly with changes in sputum eosinophils. Changes in the provocative dose of saline causing a 15% fall in FEV1 saline did not differ across the treatment groups nor did they correlate with changes in other measurements. Exhaled nitric oxide may be used to assess the dose-response relationship for the anti-inflammatory effects of inhaled beclomethasone. The relationship found in this study was linear over the dose range 0-500 microg x day(-1) soon after commencing therapy and continued over time.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Breath Tests; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Peak Expiratory Flow Rate; Saline Solution, Hypertonic; Sputum

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asian People; Asthma; Beclomethasone; Chromones; Female; Fluticasone; Forced Expiratory Volume; Genetic Carrier Screening; Glutathione Transferase; Humans; Japan; Leukotriene Antagonists; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic

The present study demonstrates the equivalent efficacy for BDP 500 microg bid given via MDI with the new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma) compared to a conventional CFC propellant (Becotide, Allen & Hanburys, UK). One hundred and sixteen adult patients with stable mild to moderate asthma (FEV1 > or = 60% of predicted normal) entered a 2-week run-in period where they maintained their own inhaled corticosteroids and were then assigned to a 12-week treatment with the test drug in a randomized, multicentre, double-blind, double-dummy, parallel-group design. Ninety-one patients completed the study period. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of daytime and nighttime asthma attacks, number of nighttime awakenings, and clinical symptoms were recorded daily by patients on a diary card. Pulmonary function tests (FEV1, FVC, PEFR, MEF50 and FEF25) were completed at study entry, at the start of treatment and every 2 weeks thereafter. Morning (08.00-10.00 AM) serum cortisol was measured at the start and at the end of treatment. Adverse events were collected for the total study period. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1 (the 95% CI of the treatments' difference was within the 5% of the LSM of BDP CFC). The other secondary pulmonary function tests measured at the clinic visit showed a satisfactory asthma control, albeit without statistically significant differences between groups. Decreases in the use of rescue salbutamol and in clinical symptoms were also reported in both groups, with no differences between them. Adverse events were reported in 81.4% of patients in the BDP HFA group and in 82.5% in the CFC group. There were 73 and 59 adverse drug reactions in the two groups, respectively; the difference was mainly due to differences in taste. No drug-related serious adverse events were reported in either group. No difference was seen for morning serum cortisol between baseline and end of treatment, or between groups. In conclusion, the BDP-HFA 134a formulation proved to be statistically equivalent to the standard BDP CFC product over 12 weeks in adult patients with mild to moderate asthma.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Least-Squares Analysis; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome; United Kingdom; Vital Capacity

Aim of our study was to evaluate if the type of nebulizer can influence the effects of steroid aerosol therapy. We considered 27 asthmatics allergic to grasses with FEV1<80% of the predictive value or methacholine PD20 FEV1<750 mcg. The patients were divided into three groups in relation to the type of nebulizer they used and treated 9 weeks by aerosol therapy with beclomethasone dipropionate bid (800 mcg). Respect to the values recorded at the beginning and at the end of the therapy we found different variations of spirometric indeces and PD20 values among the three groups. We can conclude that the type of nebulizer influences steroid aerosol therapy and, particularly, jet nebulizers seem more efficient than ultrasonic nebulizers.

Topics: Adult; Albuterol; Animals; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoconstrictor Agents; Bronchodilator Agents; Drug Delivery Systems; Female; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Mites; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Spirometry

This study was carried out with the aim of demonstrating the efficacy and tolerability of beclomethasone dipropionate (BDP) aerosol spray 500 microg b.i.d. via a spacer device (Jet, Chiesi Farmaceutici S.p.A.) using a new HFA-134a formulation or chlorofluorocarbon (CFC) propellant. After having completed a 2-week run-in period, 154 adult patients (77 in each group) with mild-to-moderate persistent asthma were randomised into two groups to receive the study treatment for a duration of 12 weeks in a double-blind, multinational, multicentre, parallel-group design. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of day- and night-time asthma attacks, number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards. Pulmonary function tests (FEV1, FVC, PEFR, FEF25-75%, MEF50 and FEF25) and vital signs were measured at the clinic at study entry, at the start of treatment and every 2 weeks thereafter. Morning serum cortisol (8.00-10.00 a.m.) was measured at the start and at the end of the treatment period. Adverse events were recorded throughout the total study period. Significant improvements over baseline were reported in both groups in terms of lung function, symptoms and use of rescue inhaled salbutamol. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1. No statistically significant differences in the comparisons between groups, except for FEF25 (P=0.044), were observed in any of the other efficacy variables. Adverse events were reported in 31% of patients in the BDP-HFA group and in 32% in the CFC group. Adverse drug reactions were 4 and 2 in the two groups, respectively. No drug-related serious adverse events were reported in either of the groups. No signs of relevant adrenal suppression were observed in both groups: 2 patients in each group had final values below the normal range. In conclusion, the BDP-HFA-134a formulation proved to be equivalent in efficacy and comparable in safety to the standard BDP-CFC product over 12 weeks in adult patients with mild-to-moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Female; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Respiratory Mechanics; Treatment Outcome

Omalizumab is a recombinant, humanized, monoclonal anti-immunoglobulin E (IgE) antibody, developed for the treatment of IgE-mediated diseases. In children with allergic asthma, it was shown to reduce the requirement for inhaled corticosteroids while protecting against disease exacerbation. Here we report the effects of treatment with omalizumab on asthma-related quality of life (AQoL) in children with allergic asthma.. This evaluation was part of a previously reported 28-week, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks) in children with allergic asthma who were well controlled on daily treatment with inhaled corticosteroids. Dosage of beclomethasone dipropionate was kept constant for 16 weeks (steroid-stable phase), then reduced over 8 weeks to the minimum effective dose (steroid-reduction phase). This dose was then maintained for the final 4 weeks. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) was administered at baseline, week 16, and week 28.. Baseline demographics, PAQLQ scores, and other data were comparable for the 2 treatment groups. At the end of the steroid-reduction phase, patients in the omalizumab-treated group reported significant improvements in the "activities" and "symptoms" domain scores as well as overall AQoL compared with placebo. More patients in the omalizumab group achieved clinically relevant (> or =0.5) changes in PAQLQ scores during the course of the study, and this difference was significant for activities and overall AQoL.. Omalizumab improves AQoL in children with allergic asthma.

Topics: Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Health Status; Humans; Injections, Subcutaneous; Male; Omalizumab; Placebos; Quality of Life; Surveys and Questionnaires; Treatment Outcome

The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as "excellent/good", compared with approximately 40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Immunoglobulin E; Injections, Subcutaneous; Male; Middle Aged; Omalizumab; Peak Expiratory Flow Rate; Quality of Life

The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.

Topics: Acetates; Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Breath Tests; Bronchial Provocation Tests; Bronchodilator Agents; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Nitric Oxide; Peak Expiratory Flow Rate; Quinolines; Sputum; Sulfides

Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control.. An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control.. In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences.. The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1).. Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness.

Topics: Acetates; Adolescent; Adult; Aged; Asthma; Beclomethasone; Cyclopropanes; Double-Blind Method; Forced Expiratory Volume; Humans; Middle Aged; Quinolines; Sulfides

The pulmonary distribution and clearance of 99m-Tc-labelled beclomethasone dipropionate (Bec)--dilauroylphosphatidylcholine (DLPC) were compared in nine asthmatic patients on inhaled steroids after a 1-week medical treatment period of long-acting beta2-agonist formoterol. The patients were given formoterol 12 microg (OxisTurbuhaler) twice daily in addition to their own regular inhaled corticosteroid therapy. Gamma lung scintigraphy and lung function tests were performed before and after formoterol treatment. The bronchodilating effect ofthe combined therapy was significant: 1-week usage of inhaled formoterol enhanced peripheral lung deposition of beclomethasone liposome and thus diminished central/peripheral deposition ratio (C/P ratio). All measured lung function values except FEV1/FVC% improved after the medication period, although statistically significant levels were not reached. A systemic positive connection was seen between enhanced lung functions and greater lung deposition measured as AUC(0-24h)/24 Beclomethasone liposome formulation maintained its long-lasting effect in connection with formoterol treatment. At the 4-h measurement, 76% of the liposome-entrapped radioactivity still remained in the lungs before and 75% after the medication period.

Topics: Administration, Inhalation; Adult; Aged; Area Under Curve; Asthma; Beclomethasone; Bronchodilator Agents; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Liposomes; Lung; Male; Middle Aged; Mucociliary Clearance; Radionuclide Imaging; Respiratory Function Tests; Technetium; Time Factors

Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy.. We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat.. The sputum eosinophil count was 63% (95% CI 24-100) lower over 12 months in the sputum management group than in the BTS management group (p=0.002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0.01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0.047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups.. A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Sputum; Treatment Outcome

The aim of this study was to compare the efficacy of BDP 200 microg bid via metered dose inhaler, using HFA-134a (Chiesi Farmaceutici S.p.A., Parma, Italy) versus CFC (Becotide, Allen & Hanburys, U.K.) as a propellant. 172 adult patients (86 in each group) with stable mild persistent asthma who completed a 7-day run-in period were randomized to receive a 6-week treatment in a double-blind, double dummy, parallel-group design; 164 patients completed the study. Morning and evening PEFR, use of rescue salbutamol, number of day-time and night-time asthma attacks, number of night-time awakenings and clinical symptoms were recorded daily on a diary card. Pulmonary function tests (FEV(1), FVC, PEFR, and MEF(50)) were measured at the clinic before and after the 1-week run-in period, and after 3 and 6 weeks of treatment. A challenge test with inhaled methacholine was completed at baseline and at the end of the treatment period to assess potential bronchial hyper-reactivity in a subgroup of subjects (n = 65; 34 HFA, 31 CFC). In accordance with asthma of mild severity (FEV(1) predicted over 90% in both groups), a small improvement in lung function compared to baseline was seen for both treatments, significantly for FEV(1) in BDP HFA and MEF(50) in both groups. The two formulations of BDP had similar efficacy for the primary outcome variable morning PEFR (ITT population mean difference 5.8 L/min; C.I. -4.9 to +16.5) as well as for the secondary outcomes of evening PEFR and clinic FEV(1). There were small improvements in methacholine PD(20) and PC20 in both groups, with no significant difference between treatments. A total of 22 and 19 drug-related adverse events were reported in the BDP HFA and CFC groups, respectively; most events were of seasonal nature or were local effects due to the use of inhaled corticosteroids. It can be concluded that the newly developed formulation of BDP given via HFA-134a seems to provide similar asthma control, compared with the same low daily dose of the active drug delivered via CFC. Further studies are needed using higher doses in moderate to severe asthma to confirm these preliminary findings.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aerosols; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests

To assess effect of a breath-actuated inhaled steroid, Fluticasone Diskhaler (Flutide) on health-related quality of life in asthmatic patients using Hyland's living with asthma questionnaire (LWAQ).. Randomly selected asthmatic patients filled out the LWAQ (the first study). Then, the eight physicians switched inhaled steroid from pressurelized metered-dose inhaler of beclomethasone (BDI) to Flutide according to their own decision. Consequently some patients were switched their prescriptions and others were not. In 12 weeks after the first study, all the patients again filled out the LWAQ (the second study).. The patients treated with Flutide were 87 and without were 159. The scale scores of the Flutide group (mean, 1.900) were significantly higher than those of the BDI-group (mean, 1.789). In the second study, there was no significant difference between the scale scores in the two groups (mean, 1.782 vs. 1.705). Among the 8 domains, only medication score significantly decreased by Flutide therapy. More than 80% of the patients favored easy handling of Flutide including no necessity of the spacer.. Flutide therapy significantly improved quality of life in asthmatic patients. The possible mechanisms are the stronger effectiveness of fluticasone propionate and improvement of adherence to inhaled steroid.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d.. Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period.. After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP.. We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Long-Term Care; Lung Volume Measurements; Male; Middle Aged; Terbutaline; Treatment Outcome

A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.. The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.. A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.. Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).. Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Prospective Studies; Treatment Outcome

The rapid growth of clinical trials sponsored by the pharmaceutical industry and conducted by community physicians raises concerns about the scientific quality of this research and the adequacy of protections for research participants. In this article, we present an in-depth ethical analysis of a recent industry-sponsored placebo-controlled study for treatment of asthma. The ethical analysis uses a proposed ethical framework for evaluating clinical research focusing on seven ethical requirements: (1) scientific value, (2) scientific validity, (3) fair subject selection, (4) favorable risk/benefit ratio, (5) independent review, (6) informed consent, and (7) respect for enrolled subjects.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Conflict of Interest; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Industry; Ethics Committees, Research; Ethics, Medical; Female; Forced Expiratory Volume; Humans; Informed Consent; Male; Mometasone Furoate; Patient Selection; Pregnadienediols; Research Support as Topic; Treatment Outcome

To assess efficiency and safety of high-dose beklometasone dipropionate in patients with bronchial asthma (BA).. The trial included 14 female and 3 male patients with moderate or severe BA (mean age 43.6 years) in declining exacerbation. The patients inhaled beklometasone dipropionate as a dose-adjusted aerosol with built-up spacer (beklojet) in a daily dose 1000-2000 mcg for 8 weeks. Changes in clinical symptoms, life quality (AQLQ) and bronchial permeability (peak flowmetry, FEV1) were registered. Concentration of H2O2 in expired air condensate was measured spectrophotometrically to evaluate activity of airway inflammation. Oral smears were studied mycologically, hydrocortisone in blood plasma was measured with enzyme immunoassay.. The treatment produced positive trend in clinical symptoms and quality of life. Bronchial permeability improved since the 7th treatment day. H2O2 significantly fell, hydrocortisone levels and fungal flora did not change significantly.. Beklometasone dipropionate in high doses for 8 weeks is effective and safe against BA.

Topics: Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Hydrogen Peroxide; Male; Middle Aged; Quality of Life

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Probability; Reference Values; Single-Blind Method; Treatment Outcome; Triamcinolone

To assess the long-term safety of hydrofluoroalkane 134a (HFA)-beclomethasone dipropionate (BDP) extrafine aerosol administered by the Autohaler compared with chlorofluorocarbon (CFC)-BDP administered by a press-and-breathe metered-dose inhaler (pMDI) and spacer (+S) in the treatment of children with asthma.. This 12-month, open-label, randomized, multicenter study enrolled 300 children who were aged 5 to 11 years and had well-controlled asthma on inhaled CFC-BDP or budesonide; 256 patients were using doses within the recommended range (200-400 microg) and were analyzed separately. Patients were randomized in a 1:3 ratio to continue on CFC-BDP+S at approximately the same dose as they were using before study entry or switch to HFA-BDP at half the daily dose.. Asthma control was well maintained in the HFA-BDP group as evidenced by lung function tests and asthma symptoms compared with CFC-BDP+S at approximately twice the dose. There were no significant differences between the HFA-BDP 100 to 200 microg and CFC-BDP+S 200 to 400 microg treatment groups in mean change from baseline in height (5.23 cm vs 5.66 cm at month 12, respectively) or mean growth velocity from day 1 to month 12 (5.27 cm/y vs 5.71 cm/y, respectively). There were no significant differences between groups in adrenal function tests or markers of bone metabolism.. In this long-term study in children with asthma, extrafine HFA-BDP provided long-term maintenance of asthma control at approximately half the dose compared with CFC-BDP+S. There were no clinically meaningful differences between HFA-BDP extrafine aerosol and conventional CFC-BDP+S with regard to growth or other systemic effects.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Child; Child Development; Child, Preschool; Chlorofluorocarbons; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Growth; Humans; Hydrocarbons, Fluorinated; Male; Respiratory Function Tests; Treatment Outcome

Options for step-down therapy include use of inhaled corticosteroids alone or in combination with a long-acting beta2-agonist.. We sought to evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM) combination administered through a dry powder inhaler (DPI; Advair Diskus) versus a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP) administered through a breath-actuated pressurized metered-dose inhaler (QVAR Autohaler).. Thirty-nine patients with uncontrolled moderate-to-severe asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI-BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n = 20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8 weeks in a double-blind, double-dummy, parallel-group design. We measured the provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20) as the primary outcome, with secondary outcomes being lung function, surrogate inflammatory markers, diary card responses, quality of life, and safety.. There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP maintained this improvement, whereas FP-SM produced a further significant improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory flow, and quality of life (symptoms and emotions) were similar to those on methacholine PD20, with a significant difference between FP-SM and HFA-BDP. Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or FP-SM administration.. After high-dose inhaled corticosteroid, stepping down with the combination inhaler conferred further improvements in bronchoprotection, bronchodilatation, and clinical control, but not inflammatory markers, compared with that seen with a medium dose of inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Hydrocarbons, Fluorinated; Middle Aged; Outcome Assessment, Health Care; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate

Clinical trials of asthma treatments usually use measures of asthma control to assess efficacy. However, it is also important to determine whether patients themselves benefit from interventions. The aim of this study was to evaluate health-related quality of life in patients with asthma switched from conventional chlorofluorocarbon (CFC) beclomethasone dipropionate (BDP) to hydrofluroalkane-134a (HFA) BDP extrafine aerosol at half the daily dose.. Open-label, 12-month, parallel-group, randomized trial.. Fifty-seven centers in four countries (United States, Belgium, the Netherlands, and United Kingdom).. Four hundred seventy-three patients with a > or = 6-month history of asthma, stable symptoms, and maintained on CFC-BDP, 400 to 1,600 microg/d.. HFA-BDP, 200 to 800 microg/d (n = 354), or CFC-BDP, 400 to 1,600 microg/d (n = 119).. The Asthma Quality of Life Questionnaire (AQLQ) and pulmonary function tests were completed at months 0, 2, 4, 8, and 12. For 1 month before each visit, patients made daily recordings of symptoms, peak expiratory flow, and beta(2)-agonist use. Two hundred ninety-six patients completed the study (HFA-BDP, 83.6%; CFC-BDP, 83.2%). At month 12, improvements in overall AQLQ scores were greater in the HFA-BDP group than in the CFC-BDP group (p = 0.0024). The number of patients who need to be treated with HFA-BDP for one to have a clinically important improvement in overall asthma-specific quality of life compared with CFC-BDP was 7.3. There was no evidence of differences (p > 0.05) between treatment groups for airway caliber, symptoms, or beta(2)-agonist use.. Clinically important improvements in the AQLQ score were observed at month 12 for HFA-BDP vs CFC-BDP, while conventional clinical indexes of pulmonary function and asthma control were similar in the two groups.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Male; Particle Size; Quality of Life; Severity of Illness Index

Flunisolide hydrofluoroalkane (HFA) has efficacy equivalent to that of flunisolide chlorofluorocarbon (CFC) at one third the dose of the CFC formulation, a reduction from 250 microg/puff for flunisolide CFC to 85 microg/puff for flunisolide HFA. Flunisolide HFA delivers a smaller particle size (1.2 microm) in solution, resulting in improved lung deposition as compared with flunisolide CFC (3.8 microm), which is delivered in suspension. An added built-in spacer has reduced oropharyngeal deposition that may result in fewer adverse events and make it easier to use. The objective of this study was to compare the year-long safety of flunisolide HFA (daily dosage 340 microg) with that of CFC beclomethasone dipropionate (BDP) (daily dosage 336 microg) and cromolyn sodium (daily dosage 6,400 microg) in children 4-11 years old with mild-to-moderate asthma. The effects of these drugs on linear growth and growth velocity were also compared. The study was a 1-year open-label, parallel-group trial. Changes in physical examinations (including growth), adverse events, vital signs, electrocardiograms, cosyntropin stimulation tests, mouth and throat cultures for Candida albicans, and laboratory findings were analyzed. Patients 4-5 years old received flunisolide HFA only. In total, 235 children were evaluated (152 receiving flunisolide HFA, 39 BDP, and 44 cromolyn). The incidence of adverse events was comparable among treatment groups; most were mild or moderate and considered unrelated to treatment. Among patients 6-11 years old, mean changes from baseline height at week 52 were 6.2 cm for the flunisolide HFA and cromolyn groups and 5.1 cm for the BDP group. Thus growth in children receiving flunisolide HFA was unaffected by 1 year of treatment. Changes from baseline in other parameters, including response to cosyntropin stimulation, were insignificant and similar among the 3 treatment groups. At the dosages studied, and following 1 year of treatment, flunisolide HFA with its small particle size and built-in spacer is safe and well tolerated in children 4-11 years old. There are no adverse effects associated with hypothalamic pituitary axis (HPA) function of flunisolide HFA, including linear growth in children 6-11 years old when compared with BDP and cromolyn sodium.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child Development; Child, Preschool; Cromolyn Sodium; Female; Fluocinolone Acetonide; Growth Disorders; Humans; Hypothalamus; Male; Pituitary Gland; Severity of Illness Index; Time Factors

The objectives of this study were to test the dose and strength proportionalities of beclomethasone dipropionate (BDP) delivered from two strengths of a pressurized extrafine solution formulation.. Thirty adults with mild, stable asthma, aged between 18 years and 70 years, completed the study; written informed consent was obtained from all patients. Each patient received, according to a randomized four-period crossover design, 100 microg BDP as two inhalations from 50-microg/actuation strength, 100 microg BDP as one inhalation from 100-microg/actuation strength, 400 microg BDP as eight inhalations from the 50-microg/actuation strength, and 400 microg BDP as four inhalations from the 100-microg/actuation strength. Patients self-administered all inhalations at the same time of day during the study. Blood samples were collected for 12 h during each period to assay for the presence of BDP and metabolites. The log-transformed pharmacokinetic data were compared for proportionality equivalence using a confidence-interval approach.. Almost all the BDP-derived material in the plasma was the active metabolite beclomethasone 17-monopropionate (17-BMP). Due to low levels, neither elimination half-life ( t(1/2)) nor the area under the plasma concentration-time curve (AUC) for 17-BMP could be calculated for the 100-microg BDP doses. Dose proportionality of the 100-microg and 400-microg BDP doses, using 17-BMP maximum plasma concentration (C(max)) was demonstrated for each strength. Strength proportionality of the 50-microg and 100-microg/actuation strengths was observed for C(max) at both dose levels and for AUC at the higher dose level. The t(1/2) of 17-BMP was found to be approximately 2.8 h.. This study demonstrated both the strength and dose proportionalities of the BDP extrafine aerosol. This important information will allow physicians maximum flexibility in prescribing this aerosol product.

Topics: Adult; Aerosols; Aged; Anti-Asthmatic Agents; Area Under Curve; Asthma; Beclomethasone; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Male; Middle Aged

In asthmatic subjects cough can be related to the degree of airway inflammation. The aim of this study was to evaluate the effect of treatment with high dose inhaled beclomethasone dipropionate (BDP) on cough threshold in asthmatic subjects. Cough threshold to inhaled capsaicin (one breath of 10(-8)-10(-4)M solution) and to citric acid (one breath of 10(-4)-1 M), expressed as provocative concentration of two (PC2) and four coughs (PC4), was measured in 16 normal and 36 asthmatic subjects. After baseline evaluation, asthmatic subjects were randomized in two groups: (a) Group A, n=20: treated with salbutamol (200 microg t.i.d.) plus BDP (500 microg t.i.d.); (b) Group B, n=16: treated with salbutamol plus placebo in the same doses. After 1 month, cough threshold and clinical and functional evaluation were repeated. After treatment, asthmatics of group A showed a significant improvement in PC4 citric acid, in total symptom and cough scores, and in PD20FEV1 methacholine. In asthmatics of group B, treatment caused no improvement in symptoms, PD20FEV1 methacoline and cough threshold. In addition, cough threshold was not different between normal and asthmatic subjects and, in asthmatics, cough threshold did not correlate with PD20FEV1 methacholine. These data confirm that cough in asthma can be partially related to airway inflammation.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Capsaicin; Citric Acid; Cough; Female; Humans; Male; Treatment Outcome

To study the therapeutic equivalence of two formulations (innovator v. generic) of beclomethasone dipropionate (BDP) 400 micrograms twice daily administered per metered dose inhaler (MDI), in adults with moderate to severe asthma.. A double-blind randomised parallel-group trial was performed with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult asthmatics on a mean daily dose of 750 micrograms inhaled corticosteroids during run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted normal and a mean histamine concentration provoking a 20% reduction in FEV1 (histamine PC20) of 0.11 mg/l were randomised to one of the two treatment groups. Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine PC20. Secondary variables were beta 2-agonist use, symptom score and nocturnal awakening. The Schuirmann two one-sided tests procedure was used for the statistical analysis. Ninety-five per cent confidence intervals (CIs) were calculated for the differences in means.. The mean differences end of treatment to baseline for the two formulations (Becotide and Beclate) respectively were: mPEF 5.6 l/min (CI - 16.4-27.6) and -22.3 l/min (CI -35.6(-)-9); FEV1 -2.9% (CI -11-5.2) and 0.2% (CI -4.8-5.2); Histamine PC20 -0.04 mg/ml (CI -0.15-0.06) and 0.02 mg/ml (CI -0.37-0.4). Changes in clinical variables were not conclusive. The mean differences with CIs for primary variables were contained within the limits set for equivalence. The sample size was sufficient to differentiate the groups for mPEF, but this was not of clinical significance.. After 8 weeks of treatment the two formulations of BDP, delivered by MDI through a large-volume spacer, were therapeutically equivalent in moderate-to-severe asthmatic adults.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Double-Blind Method; Drugs, Generic; Female; Forced Expiratory Volume; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Severity of Illness Index; Therapeutic Equivalency; Treatment Outcome

Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.. Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.. Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.. In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Bronchodilator Agents; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Osteocalcin; Peak Expiratory Flow Rate; Prospective Studies; Regression Analysis; Treatment Outcome

Mometasone furoate (MF) is a new inhaled glucocorticoid administered by dry powder inhaler (DPI).. MF-DPI was evaluated for safety and efficacy and compared with placebo DPI and beclomethasone dipropionate (BDP) administered by metered dose inhaler (MDI) in the treatment of patients with moderate persistent asthma.. Eligible patients (n = 227), 13 to 75 years of age, maintained on inhaled glucocorticoids before entering the trial, were randomized to receive: MF-DPI, 100 microg, twice daily, MF-DPI, 200 microg, twice daily, BDP MDI, 168 microg, twice daily, or placebo in a 12-week, multicenter, double-blind study.. At endpoint, FEV1 (primary efficacy variable) significantly improved for all three active treatments compared with placebo (P < .01, all comparisons). The response to MF-DPI, 200 microg, twice daily treatment was approximately twice as large as the response to MF-DPI, 100 microg, twice daily or BDP MDI treatment, although the differences between these groups did not reach statistical significance. Secondary efficacy variables including PEFR, asthma symptoms, nocturnal awakenings, and albuterol use showed similar trends. The MF-DPI, 100 microg, twice daily and BDP MDI, 168 microg, twice daily treatment groups produced comparable results for all efficacy variables.. MF-DPI, 100 microg and 200 microg, twice daily were well-tolerated and significantly improved lung function and symptom control in the treatment of patients with moderate persistent asthma. In this study, MF-DPI, 200 microg, twice daily seemed to be the most effective dosage.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Powders; Pregnadienediols; Therapeutic Equivalency

The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI.. Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials.. At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated.. Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Consumer Product Safety; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Statistics, Nonparametric

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Eosinophils; Equipment Design; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Leukocyte Count; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Treatment Outcome

Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol breath-actuated inhaler (Qvar Autohaler; BDP-AH) provides an alternative to chlorofluorocarbon metered dose inhalers or dry powder inhalers (DPIs). The aim of this six-week, open-label study was to determine whether BDP-AH demonstrates equivalent asthma control to twice the dose of budesonide (BUD)-DPI (Pulmicort Turbuhaler). Adults with symptomatic asthma inadequately controlled on BUD-DPI 400 micrograms/day and beta-agonist were enrolled. Patients (n = 193) were randomised to receive 400 micrograms/day BDP-AH (n = 98) (two puffs of 100 micrograms/actuation inhaler twice daily) or 800 micrograms/day BUD-DPI (n = 95) (two puffs of 200 micrograms/actuation inhaler twice daily). Both groups showed a statistically significant change from baseline in morning (a.m.) peak expiratory flow (PEF) at weeks 5-6 (p < 0.01), indicating study treatment improved a.m. PEF over prestudy 400 micrograms/day BUD. Changes from baseline in a.m. PEF at weeks 5-6 were 15.9 l/min for BDP-AH and 14.2 l/min for BUD-DPI; the groups were statistically equivalent (90% CI -7.02-10.44; p < -0.001 [equivalence = within +/- 25 l/min]). Other efficacy assessments (evening PEF, FEV1, asthma symptoms, beta-agonist use) confirmed the treatments were clinically equivalent. Thirty-nine (40%) patients on BDP-AH and 35 (37%) on BUD-DPI experienced at least one adverse event (p = 0.767). Four (4%) patients on BDP-AH and 3 (3%) on BUD-DPI reported increased asthma symptoms. BDP-AH at half the daily dose provided equivalent asthma control to BUD-DPI; both treatments were well tolerated.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Peak Expiratory Flow Rate; Sleep; Vital Capacity

The fractional concentration of exhaled nitric oxide (FENO) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the FENO fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients.. Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 microg/d of iBDP; period 3, 400 microg/D of iBDP; and period 4, 800 microg/d of iBDP. Spirometry, FENO, and provocative concentration of methacholine resulting in a 20% fall in FEV(1) (PC(20)) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 microg/d of iBDP for 14 days (period 2), washout on placebo treatment until the FENO was within 15% of baseline (period 3), and 200 microg/d of iBDP for 14 days (period 4).. Study A: Mean FEV(1) rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV(1) rise compared to placebo treatment, but with no significant separation of doses using FEV(1). FENO geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in FENO from placebo treatment, but with significant separation of only the 100-microg and 800-microg doses by FENO. Geometric mean (95% confidence limits) PC(20) rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC(20) from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC(20). Study B: FENO fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between FENO in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220).. FENO was superior to FEV(1) and PC(20) in separating doses of iBDP. The fall in FENO after two identical administrations of iBDP separated by placebo washout was highly reproducible.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Nitric Oxide; Prospective Studies; Reproducibility of Results

Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel).. To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks.. This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy.. Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference).. BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.

Topics: Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Particle Size; Peak Expiratory Flow Rate; Safety; Treatment Outcome

This study was carried out in an attempt to compare the efficacy and safety of fluticasone propionate (FP) at the half dose of budesonide (BUD) and beclamethasone dipropionate (BD) in childhood asthma. Ninety-six children with moderate to severe asthma (9.6 +/- 2.17 years) whose asthma was already controlled on BUD (n = 52) or BD (n = 44) were recruited into the study. In the first part of the study (the first 12 weeks) each group was followed with three weekly lung function measurements, daily diary records, and peak expiratory flow (PEF) measurements on the initial medication. At the end of 6 weeks, drugs were switched to a half dose of FP, and the subjects were followed for another 6 weeks. Blood samples were obtained for osteocalcin and plasma cortisol levels after each treatment period. In the second part of the study, 50 patients continued to take FP at the half dose of BUD or BD for another 30 weeks. Clinic visits, including lung function and PEF measurements, were conducted every 10 weeks. After 6 weeks of FP treatment, there was a small but statistically significant decrease in FEV1 and FEF(25-75) in both groups (BUD and BD) without any significant obstruction. These mild changes in lung function measurements continued during long-term follow-up. However, there was no statistically significant further decrease in any lung function parameters while receiving FP (visits 3-8) (coefficient = -0.00751 L/day, p = 0.39 for FEF(25-75) and coefficient = -0.00910 L/sec/day, p = 0.055 for FEV1). There were no significant changes in the morning and evening PEF measurements and diurnal PEF variations after 6 weeks of treatment with FP compared with BUD and BD treatments. There were no significant changes in basal cortisol and osteocalcin levels before or after 6 weeks of FP treatment (p > 0.05). The present study concluded that, although FP at the half dose of BUD or BD seems to maintain reasonable control of the disease symptoms, a mild but significant and persistent decrease in lung function parameters may indicate that FP may not be twice as potent as BUD or BD in childhood asthma by evaluation of lung functions. This conclusion must be further verified with long-term studies.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Female; Fluticasone; Follow-Up Studies; Humans; Male; Respiratory Function Tests; Time Factors

Topics: Adolescent; Adult; Aged; Ambulatory Care; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Monitoring; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Patient Participation

Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.. We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.. We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects.. There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05).. These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Biopsy; Bronchi; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Mucous Membrane; Staining and Labeling; Treatment Outcome

Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported.. To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma.. Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively.. Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period.. Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Middle Aged; Predictive Value of Tests; Quinolines; Sulfides; Time

Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. Recent studies have shown that administration of inhaled corticosteroids is associated with evidence of derangement in bone turnover. Therefore, we studied the bone mineral density (BMD) of asthmatic women receiving long-term inhaled corticosteroids and compared them with healthy individuals matched for age, sex, menopausal status and body mass index.. Thirty-two female patients with bronchial asthma, who had been using inhaled corticosteroids (beclomethasone dipropionate 750-1500 microg/day) regularly for at least 3 months, were included in the study. Bone mineral density measurements were done with dual X-ray absorptiometry in the lumbar area of the spine and the hip. Detailed laboratory examination was also done for the patients and 26 controls.. There was a significant decrease in BMD of the patient group at the lumbar region and femur as compared with normal controls. In the patients there was a significant negative correlation between the duration of therapy, daily and cumulative doses, and BMD at the lumbar region but not BMD at the femur.. These results indicate that long-term use of inhaled corticosteroids is associated with significant bone loss in asthmatic women and is especially related to the duration of therapy. Therefore, it is necessary to appropriately screen and give prophylactic treatment to those who are likely to develop osteoporosis from inhaled corticosteroid treatment.

Topics: Absorptiometry, Photon; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Mass Index; Bone Density; Calcium, Dietary; Cross-Sectional Studies; Female; Glucocorticoids; Humans; Middle Aged; Pneumonia; Time Factors; Women

There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (FcepsilonRI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of FcepsilonRI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6. More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. (ABSTRACT TRUNCATED)

Topics: Acute Disease; Anti-Allergic Agents; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Injections, Subcutaneous; Male; Omalizumab; Placebos; Treatment Outcome

Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients.. To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP).. Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast.. Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma.. Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chromones; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Membrane Proteins; Peak Expiratory Flow Rate; Receptors, Leukotriene; Treatment Outcome

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Beclomethasone; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Peak Expiratory Flow Rate; Recurrence; Severity of Illness Index; Time Factors; Treatment Outcome

We studied the effects of fluticasone propionate (FP) inhalation and the airway inflammation in beclomethasone dipropionate (BDP)-resistant bronchial asthma. Twenty-five patients who had used BDP and whose mean PEF was less then 80% were enrolled in this study. After 2 weeks of BDP inhalation. FP inhalation was administered. The total eosinophil count in the peripheral blood (/microliter), their percentage of the total WBC count (% Eos), the count in induced sputum, the serum ECP content and the induced sputum ECP content were measured before and after 6 weeks of FP treatment. There was a significant increase of morning and evening PEF, from 63.1% to 76.1% and from 63.6% to 76.2%, respectively. There was a significant positive correlation between the peripheral blood % Eos and the % increase of PEF (p < 0.01). There was also a significant positive correlation between the induced sputum % Eos and the % increase of PEF (p < 0.05). The induced sputum ECP content was still as high as 180 micrograms/l after FP treatment. The mean % PEF did not reach 80% after FP treatment. This study suggests that airway inflammation persists in some severe asthma patients despite inhalation of FP 800 micrograms.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Drug Resistance; Eosinophil Granule Proteins; Female; Fluticasone; Humans; Inflammation Mediators; Male; Middle Aged; Peak Expiratory Flow Rate; Ribonucleases; Sputum; Treatment Outcome

High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Biomarkers; Budesonide; Chronic Disease; Contusions; Creatinine; Female; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Quality of Life

Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Child; Child, Preschool; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Humans; Immunoglobulin E; Male; Ribonucleases

Clinical studies comparing the potency of inhaled corticosteroids require steep dose-response slopes (b) and minimal response variability (s), as statistical power is inversely related to the s/b ratio. To evaluate a new study model, we performed a randomized, crossover study of 12 adult asthmatics who required 800 to 2,000 microg of inhaled corticosteroids daily, and calculated s/b for 21 raw clinical outcomes and 36 mathematically derived variables based on these raw outcomes. Each of two 21-d treatment periods was preceded by 4 to 7 d of oral prednisone to maximize asthma control and minimize carry-over of previous inhaled treatment. Treatments were 100 and 800 micron/d of an HFA-134a beclomethasone dipropionate formulation. Assessments included daily home spirometry, histamine challenge, inhaled albuterol use, and asthma symptom scores. Efficacy variables with the greatest power (lowest s/b values) were A.M.FEF25-75, A.M.FEV1, and A.M.PEF, (s/b = 0.46, 0.48, and 0.59). Carry-over between treatment periods was not significant. Crossover study sample size calculations using these ratios yielded samples of 23, 25, and 37 patients, respectively. Otherwise identical parallel studies would require sample sizes of 657, 1,438, and 2,261 patients. These results support the use of a crossover asthma stability model after a short course of oral prednisone as a clinical study model for comparing topical potency of inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Peak Expiratory Flow Rate; Prednisone

Hydrofluoroalkane-beclomethasone dipropionate Autohaler (HFA-BDP AH) is a breath-actuated chlorofluorocarbon (CFC)-free metered dose inhaler in which BDP is in a solution of HFA propellant. Budesonide Turbuhaler (BUD TH) is a breath-dependent dry powder inhaler.. To test the hypothesis that half the daily dose of HFA-BDP AH would provide an equivalent control of asthma symptoms to the BUD TH.. This was an 8-week open study in patients with symptomatic moderate-to-severe asthma, previously on BUD 500-1,000 microg x day(-1), or an equivalent. After 5-14 days' run-in, patients were randomized to HFA-BDP AH 800 microg x day(-1) or BUD TH 1,600 microg x day(-1). The intent-to-treat population consisted of 111 patients on HFA-BDP AH and 98 patients on BUD TH.. Mean change from baseline in PEF in the morning (AM PEF) at week 8 was 23.95 liters x min(-1) for HFA-BDP AH and 24.46 liters x min(-1) for BUD TH. A two-sided equivalence test using the 0.51 liter x min(-1) difference gave 95% confidence intervals within a defined equivalence interval of (-infinity, 25 liters x min(-1)) indicating that the mean change in AM PEF was equivalent for the two groups. There were no significant differences in the mean change from baseline in FEV1 or beta-agonist use. Patients using HFA-BDP AH had a significantly greater mean change from baseline in the percentage of days free from shortness of breath (p = 0.05), chest tightness (p = 0.02) and nights without sleep disturbance (p = 0.04) at week 3, and wheeze (p = 0.01), shortness of breath (p = 0.02), chest tightness (p < 0.01) and daily asthma symptoms (p = 0.03) at week 8. The incidence, type and severity of adverse events were similar in each group. At week 8, the mean change from baseline in corrected urine cortisol/creatinine ratio in a subgroup of patients was -0.36 for HFA-BDP and -4.88 for BUD TH (p < 0.01).. HFA-BDP 800 microg x day(-1) provided control of moderate-to-severe asthma with efficacy and safety at least similar to BUD TH 1,600 microg x day(-1).

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Proteins; Budesonide; Cohort Studies; Creatinine; Eosinophil Granule Proteins; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; France; Germany; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Netherlands; Peak Expiratory Flow Rate; Respiratory Function Tests; Ribonucleases; Treatment Outcome

To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children.. Prospective, multicenter, randomized, double-blind, parallel-group study.. Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 (prepubertal).. Three hundred forty-three children aged 4 to 11 years with asthma. The growth population (excluding patients with protocol violations likely to affect growth measurements) included 277 patients.. Fluticasone propionate or beclomethasone dipropionate, both at a dosage of 200 microg administered twice daily via a dry powder inhaler (Diskhaler) for 12 months.. Growth velocity, lung function, and serum and urinary cortisol levels.. The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group (5.01 [SE, 0.14] vs 4.10 [SE, 0.15] cm/y; difference, 0.91 cm; 95% confidence interval, 0.63-1.20 cm; P<.001). Both treatments improved lung function, with significant differences in favor of fluticasone. Adverse events were similar in both groups, and there were no significant differences in effect on serum and urinary cortisol levels.. The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma, especially if moderate doses are required.

Topics: Androstadienes; Asthma; Beclomethasone; Body Height; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Prospective Studies

The use of short-acting beta2-agonists is associated with oral mucosa injuries that are probably provoked by decreased saliva flow and decreased concentrations of immunoglobulin (Ig)A in saliva.. To explore the effect of salmeterol, alone or combined with beclomethasone, on the health of oral mucosa, as well as its effect on saliva flow and IgA concentration in saliva.. Patients ranging in age from 6 to 15 years with moderate-persistent chronic asthma were enrolled. Patients received two 6-week treatments, one with salmeterol plus beclomethasone and the other with only salmeterol, with a 1-week washout period between treatments. Patients had oral cavity examinations and assessments of saliva flow, IgA in saliva, and total protein in saliva before the beginning and at the end of each treatment. The results of the baseline oral examinations were normal in all patients. The postsalmetrol (PS) examinations detected 13 patients with gingivitis and the postbeclomethasone-salmeterol (PBS) examinations disclosed 10 patients with gingivitis and 1 with lower-lip ulceration. Baseline saliva flow was 16.25 +/- 7.04 mm/minute (confidence interval [CI] 95% 13.67; 18.89), PS was 13.53 +/- 5.93 mm/minute (CI 95% 11.33; 15.73), and PBS was 16.57 +/- 5.54 mm/minute (CI 95% 14.51; 18.62). No statistical differences between the different assessments were found. Mean saliva IgA at baseline was 4.99 +/- 1.96 mg/dL (CI 95% 4.26; 5.71), PS IgA was 6.53 +/- 3.02 mg/dL (CI 95% 5.41; 7.65), and PBS IgA was 4.82 +/- 1.98 mg/dL (CI 95% 4.08; 5.56). PS IgA was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests). Baseline saliva IgA-to-protein ratio was 0.72 +/- 0.24 (95% CI 0.64; 0.80), PS IgA:protein ratio was 1.02 +/- 0.38 (95% CI 0.88; 1.16), and PBS IgA:protein ratio was 0.72 +/- 0.25 (95% CI 0.62; 0.82). PS IgA:protein ratio was significantly higher than the other two determinations (P < 0.05 by Bonferroni and Tukey tests).. In the present study it was demonstrated that salmeterol alone or in combination with beclomethasone induced injuries in the oral mucosa, but only salmeterol alone induced increases in the total and protein-adjusted IgA in saliva.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Child; Chronic Disease; Cross-Over Studies; Drug Interactions; Female; Humans; Immunoglobulin A; Longitudinal Studies; Male; Mouth Diseases; Saliva; Salivary Glands; Salivary Proteins and Peptides; Salivation; Salmeterol Xinafoate; Single-Blind Method

Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects.. We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months.. Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude.. We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up.. Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Signal Processing, Computer-Assisted; Sound Spectrography; Speech Acoustics; Vital Capacity; Voice Quality

This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Cross-Over Studies; Cyclopropanes; Female; Forced Expiratory Volume; Health Resources; Humans; Male; Patient Compliance; Patient Satisfaction; Quinolines; Sulfides; Time Factors; Treatment Outcome

To observe the systemic side effects of low dose inhaled Beclomethasone dipropionate (BDP) in children with mild asthma.. 30 children with mild asthma were randomly divided into 3 groups to receive treatment with inhaled placebo (group A), BDP 200 micrograms/d (group B) and BDP 400 micrograms/d (group C) respectively. Bronchial hyperresponsiveness (BHR), height growth, bone mineral density (BMD), calcium and phosphate metabolism and hypothalamic-pituitary-adrenal axis (HPAA) function were measured.. Inhaled BDP of 200 micrograms/d and 400 micrograms/d reduced BHR in mild asthmatic children and there was no significant difference between two groups [log(PD20-FEV1)]:(2.04 +/- 0.47) micrograms to (2.70 +/- 0.13) micrograms in group A and (1.94 +/- 0.46) micrograms to (3.15 +/- 0.18) micrograms in group B (P < 0.01). Serum osteocalcin, calcium, phosphate, alkaline phosphatase, basic cortisol and BMD didn't change significantly after BDP treatment in three groups (all P > 0.05) [In group A, B and C, concentrations serum osteocalcin were (29 +/- 12) micrograms/L, (22 +/- 6) micrograms/L, (31 +/- 11) micrograms/L, serum calcium: (2.49 +/- 0.11) mmol/L, (2.39 +/- 0.28) mmol/L, (2.20 +/- 0.35) mmol/L, serum phosphate: (1.8 +/- 0.6) mmol/L, (1.7 +/- 0.7) mmol/L, (1.5 +/- 0.4) mmol/L, radius BMD: (0.44 +/- 0.02) g/cm2, (0.42 +/- 0.05) g/cm2, (0.40 +/- 0.10) g/cm2, ulna BMD:(0.35 +/- 0.04) g/cm2, (0.36 +/- 0.08) g/cm2, (0.32 +/- 0.07) g/cm2, serum alkaline phosphatase: (410 +/- 113) U/L, (337 +/- 99) U/L, (351 +/- 122) U/L, serum basic cortisol: (350 +/- 86) nmol/L, (407 +/- 199) nmol/L, (365 +/- 71) nmol/L, lumbar spine (L4-5) BMD: (0.64 +/- 0.06) g/cm2, (0.59 +/- 0.08) g/cm2, (0.62 +/- 0.09) g/cm2 respectively]. Height growth had a trend of reducing after BDP treatment though not reaching statistical difference. Height standard deviation score (SDS): 1.1 +/- 0.7 to 1.2 +/- 0.9 in group A, 1.3 +/- 0.7 to 1.3 +/- 0.9 in group B and 1.1 +/- 0.7 to 1.0 +/- 0.7 in group C. Serum cortisol after ACTH stimulation reduced significantly in group C [(621 +/- 199) nmol/L to (482 +/- 97) nmol/L, P < 0.01].. The results of this study suggest that 200 micrograms/d BDP can reduce BHR significantly and has no detected systemic side effects in mild asthmatic children, and 400 micrograms/d BDP can reduce serum cortisol after ACTH stimulation. The long-term dose of BDP should be controlled to be less than 400 micrograms/d in children with mild asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Male; Single-Blind Method

Problems in using conventional inhalation aerosols, in addition to environmental reasons, have driven development of the dry powder inhalers.. To compare therapeutic equivalence and acceptability of two dry powder inhalers, Easyhaler (EH) and Diskhaler (DH), in the delivery of beclomethasone dipropionate (BDP) in the treatment of asthma.. Adult asthmatics (n = 185), previously treated with inhaled steroids, were recruited in this open parallel-group study. After a run-in period of 2 weeks during which the patients inhaled 800 microg/day of BDP via DH, the patients were randomly allocated into three groups: EH 200 group (62 patients) using EH 200 microg/dose inhaler (1 inhalation q.i.d.), EH 400 group (62 patients) using EH 400 microg/dose inhaler (1 inhalation b.i.d.), and DH group (61 patients) using DH 200 microg/dose inhaler (1 inhalation q.i.d.) for 12 weeks. The primary outcome variables were PEF and FEV(1).. The 95% CI for treatment difference in morning PEF between the EH 200 and DH groups was -16 to 23 litres/min and between the EH 400 and DH groups -18 to 21 litres/min. There was an increase in the morning PEF of 13 litres/min (p < 0.05) in the EH 200 group, and 9 and 11 litres/min in the DH and EH 400 groups. No differences between the groups were seen in the lung function parameters, in the symptom scores, in the use of rescue medication or in the incidence of adverse events. The treatments had no effects on morning cortisol levels. The patients in the EH groups compared the inhalers by using an 11-item questionnaire. In 8 questions the majority of the patients rated EH superior to DH.. The tested inhalers were therapeutically equal. However, based on the acceptability data, the EH was better accepted by the patients than DH.

Topics: Adult; Asthma; Beclomethasone; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Therapeutic Equivalency

There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Chlamydia Infections; Chlamydophila pneumoniae; Double-Blind Method; Female; Glucocorticoids; Humans; Immunoglobulin A; Immunoglobulin G; Logistic Models; Male; Severity of Illness Index

Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol (1). In this multi-centre, randomized, double-blind study, the therapeutic equivalence of two formulations of beclomethasone dipropionate (BDP) containing CFC or non-CFC (HFA134a) propellant, both delivered via the Easibreathe (Norton Healthcare Ltd, London, U.K.) inhaler, was determined in 229 asthmatic children. Each child received 100 microg doses of BDP (containing either CFC or HFA propellant) twice daily for 12 weeks. Both CFC and HFA formulations produced statistically and clinically significant improvements in patient's lung function and symptom scores when administered via the Easibreathe inhaler. The improvements in mean morning peak expiratory flow (PEF) were 41 l min(-1) and 34 l min(-1) for the BDP-HFA and BDP-CFC products respectively (P<0.001) and for mean evening PEF the improvements were 38 l min(-1) and 38 l min(-1), respectively (P<0.001). Similar findings were demonstrated for the other efficacy parameters. The two formulations were statistically equivalent with respect to efficacy. For mean morning PEF the estimated treatment difference (BDP-CFC/BDP-HFA ratio) was 102.6% (95% CI 99.1, 106.2). Similar equivalence was shown for the other efficacy parameters. Both products were well tolerated, with no difference in the adverse event profiles, effects on 24 h urinary cortisol or Candida colonisation. This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner. This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out. In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children.

Topics: Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Nebulizers and Vaporizers; Therapeutic Equivalency; Treatment Outcome

The past decade of research has led to a greater understanding of the pathogenesis of asthma and, in particular, the pivotal role of the underlying inflammatory process. Along with inheritance in atopic patients, the presence of inhaled triggering allergens are considered the predominant predisposing factors in the development of the disease. We have conducted a longitudinal clinical therapeutic study, which included 45 pediatrics patients with asthma, in order to evaluate whether the removal of any potential inhaled triggering factor, could decrease the requirement of drug based anti-inflammatory therapy. Patients admitted in this study presented at least, two monthly asthma attacks during the last four months. A single treatment with theophylline (group A), beclomethasone (group B) or salbutamol (group C), was prescribed during the first 2 weeks, along with specific instructions to avoid inhaled allergens. Regardless of the drug used, patients showed impressive and prolonged clinical improvement during 6 months, reduction of total IgE serum levels in the three groups (p < 0.02; 0.005 and 0.02 respectively) and favorable modification of force expiratory volume at the first second, forced vital capacity and flow expiratory peak. During the observation period a constant monitoring of mites allergens concentrations was performed, showing a decrease of these antigens, associated with clinical improvement, and only in those patients who remained symptomatic (group A 31%, group B 29% and group C 9%), failures performing the measures designed to reduce their exposure to environmental allergens, was demonstrated. These results suggest that reduction of inhaled triggering factors may decrease the requirement of anti-inflammatory drug therapy to control the symptoms in patients with asthma.

Topics: Adolescent; Albuterol; Allergens; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Data Interpretation, Statistical; Dust; Female; Humans; Immunoglobulin E; Inhalation Exposure; Longitudinal Studies; Male; Respiratory Function Tests; Theophylline; Time Factors

The study objective was to assess whether asthmatic adolescents who were regular users of inhaled corticosteroids preferred treatment with zafirlukast tablets or inhaled beclomethasone dipropionate (BDP), and, secondarily, to assess adolescents' inhaler technique and their opinions about treatment. An open-label, randomized, two-period, crossover study was conducted in 18 centres (primary care to specialist asthma centres) in South Africa, the UK, Finland and the Czech Republic. One hundred and thirty-two adolescents aged 12-17 years with asthma for at least 1 year and FEV1 > or = 75% of predicted, treated with short-acting bronchodilators and inhaled corticosteroids, entered the study. Patients received oral zafirlukast tablets (Accolate) 20 mg b.i.d. or inhaled BDP 100 or 200 microg b.i.d., provided by a standard pressurized metered-dose inhaler, for 4 weeks each. One questionnaire was used to determine preference (the primary outcome measure) and a second questionnaire was used to determine patients' likes and dislikes of treatment. Investigators also scored inhaler technique. Of 113 adolescents, 79 (70%) preferred zafirlukast compared with 31 (27%) who preferred the BDP inhaler (p < 0.001); three had no preference. Only 35 (29%) of 122 adolescents could use their inhaler correctly at study entry. Seventy-six patients (65%) rated zafirlukast tablets as 'very easy' to use, compared with 35 (30%) for the BDP inhaler. Both treatments were well-tolerated. This study shows that asthmatic adolescents prefer zafirlukast tablets by a ratio of 2.6:1 over inhaled BDP, and these results may have implications for improving adolescent patient compliance with asthma therapy.

Topics: Administration, Oral; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Cross-Over Studies; Female; Humans; Indoles; Male; Nebulizers and Vaporizers; Patient Compliance; Patient Satisfaction; Phenylcarbamates; Sulfonamides; Surveys and Questionnaires; Tablets; Tosyl Compounds

There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism.. This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500. Their mean age was 39 years, 67% were men, and all the women were premenopausal.. The results of peripheral quantitative computed tomographic (pQCT) measurements (primary variable) showed that, compared with baseline values, there was no loss of trabecular or integral (cortical and trabecular) bone in the distal radius or tibia in any of the patients over the 12 month study period. No consistent pattern emerged from the analysis of changes from baseline in markers of bone formation and resorption after six and 12 months of treatment.. The results of this study provide reassuring prospective one year data showing that inhaled corticosteroids, in the range of doses used, had no adverse effects on bone mass and metabolism in this group of asthmatic patients.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bone and Bones; Bone Density; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies

An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 microgram of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared.. One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits.. Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination.. It was concluded that the devices tested were equivalent in terms of efficacy and safety.

Topics: Administration, Inhalation; Adult; Aerosols; Asthma; Beclomethasone; Dosage Forms; Double-Blind Method; Equipment Safety; Evaluation Studies as Topic; Female; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Powders; Quality of Life; Therapeutic Equivalency; Treatment Outcome

A randomized, double-blind, double-dummy protocol was used to compare the safety and efficacy of beclomethasone dipropionate (BDP) delivered by a novel dry powder inhaler (DPI, Clickhaler) or by a pressurized metered-dose inhaler (MDI) plus spacer. There was a four-week run-in period, completed by 240 adult patients, who received BDP via an MDI. Patients with stable asthma were then randomized into a 12-week treatment period and received BDP (< or =2 mg/day via DPI or MDI). There were no significant differences in morning peak expiratory flow (PEF) (primary endpoint), evening PEF, overall daytime or nighttime symptom scores, or lung function parameters (forced expiratory volume in 1 sec, forced vital capacity) between DPI and MDI. The safety profiles were similar and patient acceptability for Clickhaler was high. In conclusion, BDP administered via Clickhaler was found to be clinically equivalent to an optimally used MDI. Patients with stable asthma currently receiving BDP via MDI may be effectively switched to treatment via Clickhaler DPI.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders

We examined the efficacy of inhaled corticosteroid (beclomethazone dipropionate: BDP) in elderly patients with chronic obstructive pulmonary disease (COPD). Eighty-six patients with COPD were divided into 3 groups: COPD treated without BDP (group 1, n = 26), COPD treated with BDP (group 2, n = 25), and BDP-treated COPD with asthmatic symptoms (group 3, n = 35). Pulmonary function test findings, symptoms, and prognosis for the 3 groups were retrospectively compared. No significant differences in yearly decline of FEV1.0 were observed. Of the patients treated with inhaled corticosteroid (groups 2 and 3), 30% exhibited improved FEV1.0. Of these patients, monthly decline of FEV1.0 correlated negatively with bronchial reversibility in FEV1.0 before and after inhalation of salbutamol (delta FEV1.0) (r = -0.28, p = 0.03). Cough and sputum scores were significantly improved in groups 2 and 3 (p < 0.01). Fewer admissions and episodes of acute exacerbation were noted in groups 2 and 3 than in group 1. From these results, we concluded that inhaled corticosteroid was effective in elderly COPD patients with bronchial reversibility and airway symptoms.

Topics: Administration, Inhalation; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Female; Humans; Lung Diseases, Obstructive; Male; Maximal Expiratory Flow Rate; Prognosis; Retrospective Studies

To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate (BDP), we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years, and obtained the following results. 1) 15 patients achieved step-down therapy (group A), 17 patients maintained initial dose of BDP (group B), and 11 patients required step-up therapy of BDP or daily use of oral prednisolone (group C). 2) There was no significant difference in age, sex, duration of disease, severity of disease, peripheral eosinophil counts, %FEV1 and histamine PC20 before BDP treatment among three groups. The percentage of atopic asthmatics was significantly higher in group C than in group A. 3) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups. 4) After 1 year from the start of BDP treatment, only 18% patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics. Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Male; Middle Aged; Prognosis; Retrospective Studies

Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma.. We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma.. We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (> or =1500 microg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4.. Data were available from 34 patients. After the reduction of BDP doses, FEV(1), peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P =.003).. Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Indomethacin; Male; Middle Aged; Nitric Oxide; Placebos; Respiratory Function Tests

Treatment with inhaled corticosteroids improves symptoms and reduces bronchial hyperresponsiveness (BHR) associated with asthma. Delivery of drugs into the lung is dependent on the inhaler device. Furthermore, environmental concerns regarding the use of chlorofluorocarbon propellants in pressurised inhalers and patient acceptability of inhaler devices both influence the extent of use of different delivery systems.. To compare the efficacy of beclomethasone dipropionate (BDP) administered via a novel multidose dry-powder inhaler (DPI) and a conventional pressurised metered-dose inhaler (pMDI) with spacer in patients with BHR.. A randomised, double-blind, crossover study was carried out in a group of 27 patients (aged 19-55 years) with a clinical diagnosis of reversible airway disease, who demonstrated BHR to methacholine (PD(20) < or =6.4 mg). Each patient received BDP (< or =2 mg/day) via the DPI or pMDI, for periods of 4 weeks. The randomised treatment periods were preceded by 3-week washout periods when no corticosteroid was used. Five clinic visits marked the start and end of each study phase. The primary efficacy endpoint was BHR as defined by the pharmacodynamic parameter, PD(20), which was determined at the start and end of each treatment period. Clinical endpoints including lung function, symptoms and adverse events were also evaluated.. Both treatments caused a significant decrease in BHR (p<0.05 vs. pre-treatment values). Mean +/- SD changes in log PD(20) were: DPI 0.59+/-1.29; pMDI 0.59+/-0.94 mg. There was no statistically significant difference between treatments and no evidence of a carry-over effect between treatments on BHR. Clinical efficacy and safety parameters also demonstrated no statistically significant treatment differences, and patients found the DPI easier to use.. Efficacy of BDP in reducing BHR is comparable via the DPI and pMDI plus spacer.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Equipment Design; Female; Follow-Up Studies; Humans; Male; Methacholine Chloride; Nebulizers and Vaporizers; Respiratory Function Tests; Statistics, Nonparametric

H2O2 is elevated in the exhaled air condensate in several inflammatory disorders of the lung, including bronchial asthma, and thus may reflect inflammatory processes in the airways. Exhaled H2O2 may be used to guide the anti-inflammatory treatment of patients with asthma. Therefore in this study we analysed the effect of inhaled glucocorticosteroid beclomethasone for 4 weeks on H2O2 level in the exhaled air condensate. Seventeen asthmatics and 10 healthy subjects were included to the study. Eleven patients were given inhaled beclomethasone and six were given placebo (3M Health Care). In all patients pulmonary function tests were performed. H2O2 in the expired air condensate was measured spectrofluorimetically (homovanillic acid method). Inhaled beclomethasone significantly decreased H2O2 in the expired air condensate in the active-treatment group, with a fall from baseline on day 1 which remained on day 43 (follow-up) (P<0.05). Exhaled H2O2 in the active-treatment group was significantly lower than that in placebo group (P<0.05). A negative correlation between H2O2 and forced expiratory volume in 1 sec (FEV1) on day 29 was observed. The decrease in exhaled H2O2 in the active-treatment group was accompanied by an improvement in pulmonary function tests results. Inhaled glucocorticoids reduce the level of H2O2 in the expired air condensate of asthmatic patients over a 4-week period and this may reflect their anti-inflammatory activity in lung diseases.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrogen Peroxide; Male

To assess the change in bronchial response to cumulative doses from two beclomethasone dipropionate metered-dose inhalers (MDI), each using chlorofluorocarbon (CFC) propellants, in asthma patients previously showing falls in forced expiratory volume in 1 s (FEV1) shortly after exposure to beclomethasone MDI.. A total of 18 patients were randomized to a single-blind, three-period cross-over treatment regimen, whereby each was administered increasing doses of control mixture (containing surfactant and CFC propellants) or beclomethasone, formulated as either Becloforte or Respocort (250-1000 microg per dose; cumulative dose 2000 microg). Bronchial response was measured by comparison of FEV1 values pre- and post-inhalation.. Respocort formulation produced the least post-dose mean maximum reduction in FEV1 (0.36 +/- 0.17 L; 14.3 +/- 7.2% of baseline FEV1), while the reduction caused by the control was similar (0.40 +/- 0.18 L; 16.2 +/- 9.9% of baseline FEV1). Becloforte produced a significantly greater maximum reduction in FEV1 than Respocort (0.55 +/- 0.32 L, P = 0.003; 22.0 +/- 15.3% of baseline FEV1, P = 0.005). No serious adverse events were reported, but four patients experienced falls in FEV1 of greater than 15% (three on Becloforte, one using the control).. The incidence of falls in FEV1 following use of beclomethasone MDI was low and generally not serious even in a selected population. The Becloforte preparation produced significantly more post-dose bronchoconstriction than the Respocort formulation, perhaps because of differences in the composition of the surfactant and/or CFC propellant mixtures used to formulate each of the aerosols.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchoconstriction; Chlorofluorocarbons, Methane; Cross-Over Studies; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Single-Blind Method; Surface-Active Agents

The replacement of chlorofluorocarbon (CFC) by hydrofluoroalkane has the potential to improve airway deposition of BDP. We investigated whether HFA-BDP extra-fine solution aerosol 400 microg day(-1) is as effective as CFC-BDP 1000 micro day(-1) in patients with stable, moderate asthma, having persistent bronchial hyperresponsiveness.. One hundred and fifty patients with moderate asthma from 20 centres, on inhaled steroids for < or = 3 months, entered a 4-week run-in period with 1000 microg day(-1) CFC-BDP. Patients were then allocated to a 10-week study phase, receiving CFC-BDP 1000 microg day(-1) or HFA-BDP 400 microg day(-1). Symptom score and PEF were measured daily and recorded as biweekly means. Spirometry, PC20FEV1, blood eosinophils and serum ECP were determined on days 15, 29, 43 and 71, and compared to the last visit of the run-in period. All group members were trained in a quality control centre.. Treating the population of the HFA-BDP group (n = 72) and the CFC-BDP group (n = 78) did not show significant differences in terms of symptoms, lung function, airway hyperresponsiveness and serum markers of inflammation at the end of the run-in period and the end of the study phase.. Using HFA instead of a CFC metered dose inhaler, containing less than half the daily dose of BDP, allows control of symptoms and lung function parameters, without changes in bronchial hyperresponsiveness.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Reproducibility of Results

Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Phenylcarbamates; Safety; Sulfonamides; Tosyl Compounds; Treatment Outcome

Seventy-two children (mean age, 10.1 years) with stable moderate asthma who completed a 7-day run-in period were randomized to receive a 4-week treatment with beclomethasone dipropionate (200 micrograms twice daily) administered through two different powder inhalers (Pulvinal; Chiesi Farmaceutici S.p.A, Parma, Italy and Diskhaler; Glaxo-Wellcome, Evreux, France) in a parallel group design. Sixty-nine patients completed the study. Morning and evening peak expiratory flow values, the use of rescue salbutamol, and the severity of clinical symptoms were recorded daily on a diary card. Pulmonary function tests were performed at baseline and then after 2 and 4 weeks of treatment. Pulmonary function values, daily morning and evening peak expiratory flow, and most of the clinical symptoms significantly improved, although the use of rescue salbutamol significantly decreased from the second week of treatment until the end of the study in both groups. Equivalence of efficacy between groups was demonstrated for both pulmonary function and clinical parameters. We conclude that the Pulvinal inhaler is as efficacious as the Diskhaler in beclomethasone-based therapy of asthmatic children.

Topics: Administration, Inhalation; Adolescent; Aerosols; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Female; Humans; Male; Nebulizers and Vaporizers; Patient Compliance; Respiratory Function Tests; Statistics, Nonparametric; Treatment Outcome

In the United Kingdom, about 40% of patients with asthma are homozygous for the glycine-16 beta(2)-adrenoceptor polymorphism, which predisposes them to agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor. We assessed the effects of adding treatment with either a long-acting beta(2)-agonist (inhaled formoterol, 12 microg twice daily) or a leukotriene receptor antagonist (oral zafirlukast, 20 mg twice daily) to inhaled corticosteroid therapy in patients with this genotype.. We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids. Patients were randomly assigned to receive one of three treatments (placebo, zafirlukast, or formoterol in addition to inhaled corticosteroids) for 1 week each in a crossover fashion, separated by a 1-week placebo run-in and washout period. Measurements of bronchoprotection (measured as the provocative dose of methacholine that produced a 20% decline in forced expiratory volume in 1 second [FEV(1)]), exhaled nitric oxide (a surrogate marker of airway inflammation), and symptoms were made before each treatment and 12 hours after the last dose of each treatment.. Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo: the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold (95% confidence interval [CI]: 1.1- to 2.2-fold) for zafirlukast and 1.9-fold (95% CI: 1.2- to 2.9-fold) for formoterol. As compared with placebo, zafirlukast caused a significant suppression in exhaled nitric oxide (1.7-fold difference in geometric mean values, 95% CI: 1.1- to 2.6-fold) but formoterol did not (1.2-fold difference, 95% CI: 0.8- to 1.9-fold). Diary cards showed significant (P <0.05) improvements in the peak flow with formoterol (morning and evening) and zafirlukast (evening) as compared with placebo.. Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta(2)-agonists. The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Confidence Intervals; Cross-Over Studies; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Genotype; Glucocorticoids; Glycine; Homozygote; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Nitric Oxide; Phenylcarbamates; Placebos; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Sulfonamides; Tosyl Compounds

The objective of this study was to evaluate the efficacy and safety of low doses (50 and 100 microg b.i.d.) of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) extrafine aerosol in improving asthma control. Reformulation of BDP in a new chlorofluorocarbon (CFC)-free propellant (HFA) has produced an extrafine aerosol with increased delivery of the drug to the airways of the lung. The study population comprised 270 steroid-naive patients with mild to moderate asthma (mean baseline forced expiratory volume in 1 sec [FEV1] as a percentage of predicted normal of 65%-85%). This was a 6-week, blinded, placebo-controlled, multicenter study. Patients were randomized to receive 50 or 100 microg b.i.d. HFA-BDP or HFA-placebo. Treatment with either 50 or 100 microg b.i.d. HFA-BDP resulted in a significantly greater improvement compared with placebo in FEV1 (mean change from baseline as percentage of predicted normal of 6.7%, 8.6%, and 0.4%, respectively; p < or = 0.01 active treatment groups vs. placebo), with a significant trend toward increasing improvement with increasing doses (p < or = 0.0001). Treatment also resulted in significantly greater mean changes from baseline in morning peak expiratory flow compared with placebo (29.5, 33.8, and 5.0 L/min, respectively; p < or = 0.01 active treatment groups vs. placebo). All other pulmonary function and asthma symptom measures supported these data. The study treatments were well tolerated. These results show that low doses of HFA-BDP extrafine aerosol effectively improve asthma control in adult patients with mild to moderate asthma. However, it is important that inhaled corticosteroid therapy is still given at a dose high enough to control airway inflammation as well as asthma symptoms.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Safety

We investigated whether the serum concentration of eosinophil cationic protein (s-ECP) can be used to determine when a step-down in inhaled corticosteroid therapy is indicated for patients with chronic asthma. A total of 24 adult patients, whose symptoms were well controlled with inhaled beclomethasone dipropionate (iBDP), were studied. The dosage of iBDP was reduced by half once a month until the dose reached one-quarter of the original level. s-ECP and blood eosinophil counts were determined once a month before and during the 6-month period after the step-down. In 12 patients, moderate and frequent exacerbation occurred, thus requiring a return to the initial or twice the initial dose of iBDP. Thus, the step-down here was defined as unsuccessful. In the remaining 12 patients, the symptoms were stable over the course of the 6 months, and the step-down was defined as successful. s-ECP correlated with eosinophil counts in peripheral blood (EOS) in both the successful and the unsuccessful groups. Although EOS before the step-down did not differ significantly between the two groups, s-ECP was significantly higher in the unsuccessful group (mean 35.7 microg/L) than in the successful group (mean 17.0 microg/L, p < 0.03). Thus, s-ECP appears to be a useful marker for determining when a step-down in iBDP therapy is indicated, and thus may contribute to successful long-term management of chronic asthma.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Eosinophil Granule Proteins; Eosinophils; Female; Glucocorticoids; Humans; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Prognosis; Ribonucleases

It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.. In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.. In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.. Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Compliance; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.. In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 microgram beclomethasone dipropionate (BDP) daily and inhaled beta(2) agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 microgram BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 microgram BDP) over a six month period was examined.. One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.. There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Chronic Disease; Double-Blind Method; Family Practice; Female; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Theophylline; Treatment Outcome

Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma.. 85 patients with moderate to severe asthma taking high doses (> or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists.. Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group.. Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed.

Topics: Administration, Inhalation; Administration, Oral; Anti-Allergic Agents; Anti-Asthmatic Agents; Arylsulfonates; Asthma; Beclomethasone; Circadian Rhythm; Cytokines; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Sulfonium Compounds; Th2 Cells

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low-dose inhaled corticosteroids. Randomized, double-blind, placebo-controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run-in weeks, on treatment with low-dose inhaled beclomethasone dipropionate (BDP, 250 microgram b.i.d. in the last 3 months). At the end of the run-in, all patients underwent a methacholine challenge test and sputum induction (T1). They then stopped therapy and received either placebo (20 subjects, study group) or BDP at the same dose as in the previous 3 months (10 subjects, control group). They continued to monitor PEF and symptom score for 3 months, or until asthma symptoms recurred (diurnal and nocturnal symptom score >/=2 on two consecutive days). At the end of the study (T2), i.e., either within 5 days from the beginning of asthma symptoms or after 3 months in subjects without recurrence of asthma symptoms, all subjects repeated the methacholine challenge test and sputum induction. In the placebo-treated group, sputum eosinophils at T1 were significantly higher in subjects who subsequently developed recurrence of asthma symptoms (n = 7) after cessation of treatment than in subjects who remained asymptomatic for 3 months (8.2% [0-56.6] vs 0.9% [0-11], P < 0.05). At the time of recurrence of asthma symptoms, sputum eosinophil percentages significantly increased (from 8.2% [0-56.6] to 16.6% [5.8-73.6], P < 0.05). The positive predictive value of sputum eosinophils for the recurrence of asthma symptoms was 71%, while the negative predicting value was 84%. In the BDP-treated control group, none of the subjects experienced recurrence of asthma symptoms, and sputum eosinophil percentages measured at the beginning (T1) and at the end (T2) of the study were similar. Sputum eosinophil percentages may vary over a wide range in asthmatic subjects, although regularly treated and apparently well controlled. However, high sputum eosinophil percentages are related to early recurrence of asthma symptoms after cessation of inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Eosinophils; Female; Glucocorticoids; Humans; Leukocyte Count; Male; Predictive Value of Tests; Recurrence; Sputum

The hypothesis that eosinophilic airway inflammation is present in many patients presenting with respiratory symptoms suggestive of asthma but with normal lung function was tested. Thirty-six consecutive patients presenting with these features were studied. Twenty-five asthmatics and 43 healthy volunteers served as control groups. Signs of eosinophilic inflammation in blood and induced sputum were studied. Patients with respiratory symptoms were single-blindly treated with inhaled beclomethasone dipropionate (BDP), 800 microg daily, or placebo for 3 months, and re-examined at 3 months and 1 yr. Patients with respiratory symptoms had higher numbers of blood and sputum eosinophils than healthy persons (p<0.0001), but the degree of eosinophilic inflammation was less pronounced than in asthmatics (p<0.01). Three-month's treatment with BDP significantly reduced total symptom score (p<0.001), cough score (p<0.0001), and the number of blood eosinophils (p<0.01). For cough alone, the improvement was significant compared with placebo (p<0.05). The patients were followed-up for 1 yr, and 17 (55%) still had symptoms but retained normal lung function. Four (13%) patients had developed asthma and another 10 (32%) had become free of symptoms. Using lung function measurements and induced sputum analyses, a group of patients with symptoms suggestive of asthma and signs of eosinophilic airway inflammation but without enough airflow variability to be diagnosed as asthmatics were detected. They seemed to respond favourably to inhaled beclomethasone dipropionate treatment.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Cells; Eosinophilia; Female; Follow-Up Studies; Humans; Inflammation; Lung; Male; Middle Aged; Reference Values; Respiratory Tract Diseases; Single-Blind Method; Sputum

The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Prednisolone; Treatment Outcome

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Chronic Disease; Clodronic Acid; Fluticasone; Humans; Infusion Pumps; Male; Middle Aged; Osteoporosis

To investigate the effect of small dose of oral theophyllin combined with low dose of inhaled beclomethasone dipropionate (BDP) on clinical symptoms, bronchial responsiveness and hypothalamic-pituitary-adrenal axis (HPAA).. 43 patients with mild-moderate bronchial asthma were randomly divided into A and B groups. 21 subjects in group A were treated with oral substained release theophyllin (Protheo) (200 mg/night) and inhaled BDP (300 micrograms/day); 22 cases in group B received inhaled BDP (600 micrograms/day) and oral placebo.. Before and 13 weeks after the treatment, symptom scores, peak flow(PEF), and peak flow rate (PEFR) for group A were (1.8 +/- 0.9) and (0.10 +/- 0.30), (295 +/- 98) L/min and (444 +/- 150) L/min, (22 +/- 8)% and (9 +/- 3)% respectively, and those for group B were (1.90 +/- 0.70) and (0.10 +/- 0.30), (328 +/- 129) L/min and (441 +/- 146) L/min, (24 +/- 7)% and (9 +/- 3)% respectively, which were remarkably improved in both groups (P < 0.01), and bronchial provocation responsiveness to histamine tests (BHR) in both groups were also improved significantly (P < 0.01). There were no differences between two groups (P < 0.05). Frequency of using inhaled beta 2 agonist to relieve nocturnal asthmatic attacks in group B (3.9 +/- 1.7) was significantly greater than that in group A (1.3 +/- 1.0, P < 0.05). Plasma ACTH concentrations, basic cortisol levels and cortisol responses to ACTH before and 13 weeks after the treatment in group B were (31 +/- 13) ng/L and (20 +/- 8) ng/L, (95 +/- 50) micrograms/L and (86 +/- 48) micrograms/L, (156 +/- 98)% and (74 +/- 46)% respectively, which were decreased significantly after the treatment (P < 0.05). There were no such changes in group A.. It was suggested that small dose of oral theophylline combined with low dose of inhaled BDP might have the same effect on relief of clinical symptoms and bronchial responsiveness, without suppression on HPAA function, comparing with relatively higher dose of inhaled BDP.

Topics: Administration, Inhalation; Administration, Oral; Adrenocorticotropic Hormone; Adult; Aged; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Theophylline; Time Factors; Treatment Outcome

The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis.. A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy (inhaled beta-agonist and CFC-BDP [< or = 400 microg/d]). A short course of oral prednisone, 30 mg/d for 7 to 12 days, was followed to establish the patients were steroid responsive and to provide an "in-study" baseline of "optimal" asthma control.. A total of 347 patients were then randomized to HFA-BDP 400 microg/d, CFC-BDP 800 microg/d, or HFA-placebo for 12 weeks.. Morning peak expiratory flow (AM PEF) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment. All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo. The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported.. These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied, but at half the total daily dose.

Topics: Adult; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Drug Combinations; Female; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Peak Expiratory Flow Rate; Treatment Outcome

To examine the efficacy of an inhaled steroid, when added to a standard regimen of beta-agonist therapy, in the treatment of patients with mild to moderately severe asthma in the emergency department.. A convenience sample of adult patients with asthma (FEV1 % predicted 40% to 69%) presenting to the ED was randomly assigned in a double-blind fashion into 2 treatment groups. The first group received 2.5 mg nebulized salbutamol plus 1 mg (4 puffs) of beclomethasone dipropionate (BDP) at baseline, 30 minutes, and at 1, 2, and 4 hours, delivered by a metered-dose inhaler (MDI) attached to a spacer device (Vent-AH-aler, Glaxo). The second group was given the same salbutamol regimen plus MDI placebo through the Vent-AH-aler. The primary endpoint was improvement in FEV1 %predicted at 6 hours.. Of 54 patients enrolled, 28 were assigned to the BDP group and 26 to the placebo group. Spirometry improved significantly in both groups over the 6 hours compared with baseline (ANOVA, P <.001). At 6 hours, the mean absolute improvement in FEV1 % predicted for BDP was 18% versus 17% for placebo (95% confidence interval for the absolute difference of 1% [-8% to 10%]). The proportion of patients in the BDP group who were hospitalized was 7% compared with 19% for patients in the placebo group (95% confidence interval for the difference of 12% [-6%, 30%]).. In this group of patients with mild to moderately severe asthma, 5 mg BDP delivered by MDI during the initial 4 hours of an emergency visit was of no added benefit over standard therapy, as measured by improvement in FEV1 % predicted at 6 hours. However, a trend toward a difference in admission favoring BDP was observed. [Afilalo M, Guttman A, Colacone A, Dankoff J, Tselios C, Stern E, Wolkove N, Kreisman H: Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: A randomized clinical trial.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Forced Expiratory Volume; Humans; Male; Spirometry

Salmeterol inhaled twice-daily is now being used more frequently as additional treatment in asthma insufficiently controlled by inhaled corticosteroids. We compared oral bambuterol in a dose of 20 mg taken once daily in the evening with inhaled salmeterol at 50 microgram taken twice daily in 126 asthmatic patients (60 bambuterol, 66 salmeterol) aged 18 to 74 yr who were treated for at least 4 wk with inhaled corticosteroids at a constant dose of 400 to 2,000 microgram/d or with oral corticosteroids at /= 15% overnight decrease in peak expiratory flow (PEF) on 3 of the preceding 7 d, in order to be randomized into this double-blind, double dummy, multicenter parallel group study (2-wk run-in period and 6 wk of treatment). There was no significant difference between bambuterol and salmeterol in morning change from baseline in PEF (p = 0.53). The median increases in morning PEF were 50 L/min for bambuterol and 55 L/min for salmeterol. Other variables (evening PEF, percent of overnight decrease in PEF, number of awakenings, percent of nights with an awakening, number of puffs of rescue medication, asthma symptoms during the day and night, and mean tremor score) also showed no significant difference between bambuterol and salmeterol. Both treatments, at the doses given, were well tolerated. Once-daily oral bambuterol is a convenient, effective, and less expensive alternative to twice-daily inhaled salmeterol for treating nocturnal asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Terbutaline

Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.. To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.. Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.. 36 sites worldwide.. 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.. Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo.. Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.. Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.. Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Cell Count; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Eosinophils; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos; Quality of Life; Quinolines; Sulfides

Current guidelines on asthma management recommend the early use of inhaled corticosteroids. Recent studies of patients with moderate to severe asthma show that the addition of salmeterol is superior to a further increase of the steroids. In this study with adult, mild persistent asthma patients, we compared the effects of adding salmeterol 50 microg b.i.d. versus beclomethasone dipropionate (BDP) 200 microg b.i.d. (both via Diskhaler dry powder inhaler) to the low-dose inhaled steroids. A double-blind, randomized, parallel-group study was conducted with a run-in period of 2 weeks and a treatment period of 12 weeks. Patients (n = 233) were randomized with a peak expiratory flow (PEF) reversibility of 22 +/- 10% (mean +/- SD) in the run-in period. The morning PEF was 84 +/- 17% predicted and the age was 42 +/- 14 years (45% males). The average prestudy inhaled steroid dose was 361 microg daily. Within a week of salmeterol treatment the daily PEF recordings reached maximal levels. At the end of the treatment period the evening PEF remained significantly better in the salmeterol group than in the BDP group (p = 0.036). The PEFs, measured at the general practitioners' (GPs') office, were at least 95% of the predicted values and the post-salbutamol values at the end of both treatments. However, the salmeterol group had already obtained this level after 2 weeks and differed significantly from the beclomethasone group (p = 0.003 for percent predicted and p = 0.0007 for post-salbutamol PEF values). The symptom scores and the use of rescue medication showed a similar profile. Quality of life improved with both treatments, but without significant statistical differences between the groups. The frequency of adverse events, typical for beta2-agonists, was low and showed no differences between the groups. These results showed that the addition of salmeterol is at least as effective as adding beclomethasone in normalizing peak flows and improving asthma control in mild persistent asthma patients. Furthermore, salmeterol has a much faster onset of action.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Salmeterol Xinafoate; Steroids; Treatment Outcome

One week of regular treatment with salmeterol can induce tolerance to the protective effect of a beta2-agonist on early airway response to allergen (EAR). The objective was to assess whether inhaled corticosteroids revert tolerance to salmeterol.. The study had a randomized, double-blind, placebo-controlled design.. Twelve subjects with mild allergic asthma and positive result of specific bronchial provocation test (sBPT) to allergen underwent three sBPTs, separated by 1 week. sBPT was done in all subjects after a single dose (T1) and after 1 week of regular treatment with inhaled salmeterol (50 microg bid) (T2) in order to induce tolerance. Subjects were then randomized to receive either the same dose of salmeterol + beclomethasone dipropionate (BDP, 500 microg bid) (group 1, n = 6) or placebo + BDP (group 2, n = 6) for 1 week before sBPT (T3).. After a single dose of salmeterol (T1), all subjects were protected against EAR, whereas after 1 week of regular treatment, the protective effect of salmeterol was totally or partially lost (T2). Maximum FEV1 percent fall (MaxdeltaFEV1%) after allergen inhalation was significantly higher at T2 than at T1. All subjects except one of group 1 were protected against EAR after salmeterol + BDP (T3), and MaxdeltaFEV1% at T3 (median, 12%; range, 4 to 6%) was significantly lower than T2 (median, 22%; range, 12 to 43%; p < 0.05 by Wilcoxon test). Subjects of group 2 did not show any significant protection against EAR after placebo + BDP treatment (T3) MaxdeltaFEV1% at T2 (median, 31%; range, 9 to 40%) and T3 (median, 31%; range, 3 to 42%; not significant).. In conclusion, the addition of inhaled BDP partially restored the bronchoprotective effect of salmeterol on allergen challenge that was lost after 1 week of regular treatment with salmeterol alone. This ability of BDP in reverting tolerance cannot be ascribed to a direct effect of corticosteroids per se on allergen challenge in this group of asthmatics.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Salmeterol Xinafoate

A high serum immunoglobulin (Ig)E level is considered a potent predictor for the development of asthma and IgE is targeted for treatment of asthma. Although inhaled corticosteroids are well established in the treatment of asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma remain uncertain.. We therefore examined asthma symptoms, concentrations of total serum IgE and specific IgE antibodies to selected allergens, blood eosinophil counts and lung functions before and 3 months after treatment with either inhaled beclomethasone dipropionate (BDP; 800 microg/day) (n = 7) or inhaled beta2-agonists alone (n = 7) in patients with atopic asthma in a randomized, double-blind, parallel-group controlled trial.. Inhaled BDP significantly improved asthma symptom scores and forced expiratory volume in 1 s, and decreased blood eosinophil counts, total serum IgE levels and specific IgE antibodies to house dust mite and cedar. Decreases in total serum IgE significantly correlated with an improvement in asthma symptom scores. In contrast, none of parameters altered in patients with atopic asthma treated with inhaled beta2-agonists alone.. Inhaled corticosteroids may improve the subsequent clinical course of atopic asthma in association with a reduction of serum IgE levels.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Eosinophils; Female; Humans; Immunoglobulin E; Male

Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few.. We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma.. Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards.. Fluticasone propionate treatment resulted in significantly (P

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Tachycardia

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.

Topics: Amino Acids; Asthma; Beclomethasone; Biomarkers; Bone Density; Bone Remodeling; Child; Child, Preschool; Female; Glucocorticoids; Humans; Male; Osteocalcin

Since equivalent efficacy is achieved with lower doses of the reformulated beclomethasone dipropionate in the chlorofluorocarbon (CFC)-free propellant HFA-134a (HFA) than with the original CFC-beclomethasone dipropionate formulation, it is possible the HFA-beclomethasone dipropionate may have less safety concerns than the CFC formulation. Despite its chronic use, the steady-state pharmacokinetics of beclomethasone dipropionate has never been studied before. This double-blind study examined adrenal effects and pharmacokinetics after 14 days of dosing with HFA-beclomethasone dipropionate. Forty-three steroid-naïve asthmatic patients were randomised into 5 parallel groups and dosed every 12 h for 14 days with: HFA-placebo; 200, 400 or 800 microg day(-1) HFA-beclomethasone dipropionate; or 800 microg day(-1) CFC-beclomethasone dipropionate. After two weeks of dosing, the 24-h urinary free cortisol of all but one patient remained within the normal range, showing that all doses were well tolerated from a systemic safety perspective. The active HFA-beclomethasone dipropionate treatment groups showed a dose-related fall in 24-h urinary free cortisol. Total-beclomethasone (beclomethasone dipropionate and metabolites) pharmacokinetics after either the first dose of HFA-beclomethasone dipropionate or CFC-beclomethasone dipropionate were not substantially affected by subsequent doses. The extent of drug absorption from 800 microg day(-1) HFA-beclomethasone dipropionate and CFC-beclomethasone dipropionate was in the ratio of 1.7 : 1. A non-linear correlation between 24-h urinary free cortisol and the pharmacokinetic parameters was observed, reflecting smaller changes in 24-h urinary free cortisol than in pharmacokinetics as the dose was increased. No clinically meaningful change in the pharmacokinetics of beclomethasone dipropionate plus metabolites was seen on multiple dosing. The greater systemic availability of HFA-beclomethasone dipropionate was still associated with adrenal effects comparable with that of the CFC formulation at the same dose.

Topics: Administration, Inhalation; Adrenal Glands; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biological Availability; Chlorofluorocarbons; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Nebulizers and Vaporizers; Particle Size; Placebos; Smoking

We undertook a community based case-control study to measure the effect of pranlukast on the reduction of inhaled steroid in adult asthmatics. Forty-one adults completed a run-in period of 4 weeks on 800 microgram of beclomethasone dipropionate (BDP) documenting twice daily peak expiratory flow (PEF) and symptom score and therapeutic score on a standard diary. Forced expiratory volume in one second (FEV1.0), V50, V25 was measured once during the run-in period. Patients were then randomized to receive either pranlukast with 400 microgram of BDP or 400 microgram alone for 8 weeks. There was no difference in the symptom score and therapeutic between the two groups at any time point. However, morning and evening % PEF run-in expressed as a % of the PEF average during the run-in period was significantly lower at 8 weeks in the groups without pranlukast. There were subjects in the group without pranlukast (35.3%) compared to those with (20.8%) who had a 10% or more reduction in % PEF from the run-in period. The patients with an FEV1.0 < 80% predicted who were randomized to the control group were more likely (5 of 7) to have a fall in % PEF run-in and those randomized to received pranlukast were less likely to have a fall in % PEF run-in though this was not significant (2 of 6). In this study, pranlukast has demonstrated steroid sparing effect. Severe asthmatics (FEV1.0 < 80%) who deteriorate after reduction of inhaled steroid may benefit most from pranlukast. Larger studies are now required to explore this important effect.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Case-Control Studies; Chromones; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Respiratory Function Tests

Home exposure to high levels of house dust mite allergen has been shown to aggravate airways reactivity and asthma.. The purpose of this study was to determine whether specific house dust mite control measures could reduce exposure levels and asthma severity.. This double-blinded, randomized trial compared asthma progression over 1 year in children whose homes received standard environmental control intervention with those whose homes received aggressive intervention for dust mite elimination. The primary end point was doubling in PD20 methacholine.. Symptom scores and quality-of-life scores were similar for the standard and aggressive intervention groups. PD20 methacholine doubling occurred in 9 members of the aggressive intervention group vs 4 control patients (P <.05). Dust mite levels decreased in the aggressive intervention homes compared with the standard intervention homes (P <.05).. Aggressive dust mite intervention decreased dust mite levels and improved bronchial hyperresponsiveness.

Topics: Adolescent; Air Pollution, Indoor; Allergens; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antigens; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Cromolyn Sodium; Dust; Environmental Pollutants; Glycoproteins; Humans; Methacholine Chloride; Mites; Respiratory Function Tests; Socioeconomic Factors; Triamcinolone

Recent investigations revealed that in patients with bronchial asthma the same anti-inflammatory effect is achieved by inhalation of half the dose of budesonide by a Turbuhaler (i.e. by using corticosteroid in powder form) as by a full dose of beclomethasone driven into the lungs by compressed chlorofluorocarbons (i.e. MDI = pressure dosage inhalator). The objective was to assess whether there is a difference between 12-week treatment with budesonide Turbuhaler in a smaller dose of 400 micrograms/day and treatment with beclomethasone dipropionate MDI 800 micrograms/day.. After an initial two-week period of the 227 patients with mild or medium severe asthma who had not taken corticosteroids for three months, into the budesonide Turbuhaler group 94 patients were included and into the beclomethasone MDI group 99 patients. Characteristics: group treated with budesonide (46 men, 48 women, mean age 38 years, FEV1 78% of appropriate values). Group treated with beclomethasone (51 men, 48 women, mean age 39 years, FEV1 81.5% of appropriate values). Morning and evening values of the peak expiration rate (PEF) increased significantly after budesonide treatment 2 x 200 micrograms/day) as compared with beclomethasone treatment (2 x 400 micrograms/day). Differences of morning PEF between budesonide and beclomethasone: 47:28 l/min, p < 0.05, differences of evening PEF: 32:10 l/min., p < 0.027. The number of dyspnoic attacks declined after both types of treatment, as well as the amount of inhaled bronchodilatating substances (terbutalin Turbuhaler). The differences between drugs were however not statistically significant.. Budesonide Turbuhaler, 400 micrograms/day when administered to patients with bronchial asthma was at least as effective as beclomethasone MDI, 800 micrograms/day. The increase of morning and evening PEF values was after budesonide significantly higher than after beclomethasone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Humans; Male; Middle Aged

While inhaled steroids (IS) are increasingly recognized as having a more rapid onset of action than was once thought, little is known about the early changes in objective measures of respiratory function that follow the inhalation of repeated doses. These early effects were examined in a randomized, double-blind, placebo-controlled, crossover study of 20 children aged 10-16 years with stable mild asthma. Beclomethasone dipropionate (BDP) 2,000 mcg, fluticasone propionate (FP) 400 mcg, and placebo were given twice daily for three doses. Airway hyperreactivity (AHR) to methacholine (PC20), pulmonary function tests (PFT: FVC, FEV1, FEF25-75%), and the rate of recovery from methacholine-induced bronchospasm following administration of salbutamol were determined at 8 h (after 1 dose) and at 32 h (after three doses). At 8 h, minor improvements in AHR were demonstrated, averaging 0.32 doubling doses in PC20. At 32 h, significant improvements in AHR and PFTs were present, averaging 0.92 doubling doses in PC20, 3.96% of predicted values in FEV1, and 7.74% of predicted values in FEF25-75%. No significant changes occurred in FVC. There were no significant differences between the effects of BDP and FP. Inhaled steroids were associated with a slower response to salbutamol following methacholine challenge testing at 32 h. We conclude that IS, given in repeated high doses, result in significant improvements within 32 h in both AHR and PFTs, along with changes in response to beta2 agonists. These effects are likely to be the result of the topical activity of IS.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Respiratory Function Tests; Respiratory Mechanics; Treatment Outcome

There is a paucity of data comparing the long-term safety and efficacy of long-acting inhaled beta2-agonists versus low-dose inhaled corticosteroids in the treatment of asthma.. To compare the safety and efficacy of salmeterol xinafoate, beclomethasone dipropionate (BDP), and placebo over a 6-month treatment period in patients with persistent asthma.. Salmeterol (42 microg twice daily), BDP (84 microg four times daily), or placebo was administered via metered-dose inhaler to 386 adolescent and adult inhaled corticosteroid-naive patients in a randomized, double-blind, double-dummy, parallel-group study. Eligible patients demonstrated a forced expiratory volume in 1 second (FEV1) from 65% to 90% of predicted values. Pulmonary function, symptom control, frequency of asthma exacerbations, bronchial hyperresponsiveness (BHR) to methacholine challenge, and adverse events were assessed.. There were few statistically significant differences between the two active treatments over 6 months of therapy. Asthma symptoms and lung function were significantly improved with both salmeterol and BDP compared with placebo (changes from baseline in FEV1 of 0.28 L (SE = 0.04) and 0.23 L (SE = 0.04), respectively, compared with 0.08 L (SE = 0.04); P < or = .014). There were no significant differences among the treatment groups with respect to the distribution of asthma exacerbations over time. Both salmeterol and BDP significantly reduced BHR compared with placebo (P < or = .033; changes from baseline of 1.29 (SE = 0.26) and 1.42 (SE = 0.24) doubling doses at 6 months, respectively, compared with 0.24 (SE = 0.29) doubling dose for placebo). No rebound effect in BHR was seen upon cessation of any of the three treatment regimens. There were no clinically important differences in the safety profiles among the three treatments.. Both salmeterol and BDP are effective and well-tolerated when administered for 6 months to inhaled corticosteroid-naive patients with persistent asthma.

Topics: Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Child; Double-Blind Method; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Placebos; Salmeterol Xinafoate; Therapeutic Equivalency

A variety of methods are available for analysing repeated measurements data where the outcome is continuous. However, there is little information on how established methods, such as summary statistics and repeated measures analysis of variance (RMAOV), compare in practice with methods that have become available to applied statisticians more recently, such as marginal models (based on generalized estimating equation methodology) and multilevel models (that is, hierarchical random effects models). The aim of this paper is to exemplify the use of these methods, and directly compare their results by application to a clinical trial data set. The focus is on practical aspects rather than technical issues. The data considered were taken from a clinical trial of treatments for asthma in 240 children, in which a baseline and four post-randomization measurements of outcomes were taken. The simplicity of the method of summary statistics using the post-randomization mean of observations provided a useful initial analysis. However, fixed time effects or treatment-time interactions cannot be included in such an analysis, and choice of appropriate weighting when there is substantial missing data is problematic. RMAOV, marginal models and multilevel models generally provided similar estimates and standard errors for the treatment effects, although in one example with a relatively complex variance structure the marginal model produced less efficient estimates. Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right, and that they can be naturally extended to handle multivariate outcomes.

Topics: Adolescent; Analysis of Variance; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Data Interpretation, Statistical; Glucocorticoids; Humans; Models, Statistical; Multicenter Studies as Topic; Multivariate Analysis; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic

Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Contusions; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Prospective Studies; Skin Diseases

The objectives of this study were to assess the acceptability and efficacy of Jet (a metered dose inhaler with a 100 ml chamber giving 250 micrograms beclomethasone dipropionate per puff) in patients with mild to moderate asthma using a dose-for-dose schedule in substitution for their standard metered dose inhaler with or without an inhalation chamber. An open trial was conducted over 5 weeks in 356 asthma patients treated with inhaled corticosteroids at a mean 914 +/- 198 micrograms/24 h dose. beta 2-agonists were used by all patients, either systematically (prescription) or as needed. Prior to the study, 27% of the patients used a standard metered dose inhaler with a large-volume inhalation chamber and 73% used a standard metered dose inhaler alone. The rate of nocturnal, early morning, and diurnal symptoms and cough decreased by 31.4, 33.4, 46.9, and 37.0% respectively and the variability of peak expiratory flow rate fell from 2 +/- 0.08% to 0.9 +/- 0.02% in the group using the metered dose inhaler with the chamber and from 1.3 +/- 0.04 to 0.5 +/- 0.01% in the group using the standard metered dose inhaler. The investigators determined that treatment efficacy was good or excellent in 94.8%. These findings should be confirmed by studies comparing Jet directly with other inhalation chamber systems or with standard metered dose inhalers. For 97.5% of the patients, it was easy to learn to use Jet and 88.2% of the patients felt no discomfort when using Jet; 64.8% of the patients stated they experienced clinical improvement. At the end of the trial, 77.9% of the patients (76.3% of those who used the inhalation chamber during the study and 78.4% of those who used the metered dose inhaler alone) stated they preferred Jet over their prior system.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Respiratory Therapy; Time Factors

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Antioxidants; Asthma; Beclomethasone; Catalase; Double-Blind Method; Erythrocytes; Female; Glucocorticoids; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Male

Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids have reduced bone mass. This prospective 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids. Patients (n = 33) (males aged 18-50 yrs, females aged 18-40 yrs) on inhaled corticosteroids 1,000-2,000 microg x day(-1), were randomized in a double-blind fashion to either fluticasone propionate (FP) 1,000 microg x day(-1) or beclomethasone dipropionate (BDP) 2,000 microg x day(-1). In parallel, three open control groups of the same age range were studied: asthmatics (n = 8) receiving low dose inhaled corticosteroids (< or =400 microg x day(-1)) (group A); chronic, severe asthmatics (n = 8) receiving oral corticosteroids (> or =10 mg x day(-1) (group B); and healthy untreated volunteers (n = 7) (group C). Bone densitometry scans (quantitative computed tomography (QCT) of spine; dual X-ray absorptiometry of spine, femoral neck, and single photon absorptiometry of forearm) were performed at baseline and after 6, 12 and 24 months of treatment. Biochemical bone marker measurements (serum osteocalcin, bone alkaline phosphatase, pro-collagen type 1 carboxy terminal propeptide, deoxypyridinoline and C-telopeptide of type 1 collagen) were collected every 3 months. Fifteen FP (mean age 36 yrs, six male) and 9 BDP patients (mean age 33 yrs, five male); completed the study. At 0 months, mean bone mineral density (BMD) was lower in patients receiving inhaled corticosteroids (both low dose and high dose) than in normal volunteers. In the FP-treated group, mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline, whereas there was some decline in the BDP-treated group. The treatment difference between FP and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months (p = 0.006) and 24 months (p = 0.004). This study suggests that over 24 months, changes in bone density are minimal in patients on high-dose inhaled corticosteroids.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Adult; Alkaline Phosphatase; Androstadienes; Asthma; Beclomethasone; Bone and Bones; Bone Density; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Osteocalcin; Peptide Fragments; Procollagen; Tomography, X-Ray Computed

Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown.. We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma.. Inhaled BDP, 800 microg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined.. We observed significant decreases in collagen type III deposition (P <.01) and the expression of submucosal MMP-9 (P <.01) and a significant increase in the expression of submucosal TIMP-1 (P <.05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial (r (s ) = 0.37, P <.05) and submucosal expression of MMP-9 (r (s ) = 0.47, P <.01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group.. Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Biopsy; Bronchi; Collagen; Collagenases; Female; Humans; Inflammation; Male; Matrix Metalloproteinase 9; Middle Aged; Mucous Membrane; Placebos; Tissue Inhibitor of Metalloproteinase-1

The Spacehaler (Evans Medical Ltd, Leatherhead, U.K.) is a new, compact, inhaler device containing the same aerosol canister as a conventional metered dose inhaler (MDI). However, the design of the Spacehaler has been shown to reduce the velocity of the aerosol, thus reducing the proportion of non-respirable particles delivered to the patient. This study compared radioaerosol deposition patterns following inhalation of 250 micrograms of beclomethasone dipropionate from the Spacehaler and a conventional MDI (Beclazone, Norton Health Care, Harlow, U.K.). After rigorous in vitro validation of the radiolabelling technique, 12 asthmatic subjects (seven men aged 20-69 years, mean baseline FEV1 2.59 1 (SD 0.55 1) received one dose of 99mTc-labelled beclomethasone dipropionate 250 micrograms via either a Spacehaler or MDI on each of two study days in a randomized cross-over manner. All subjects had been taught the required inhalation technique before the dose was administered. Inhalation details were recorded using a spirometer connected in series with the device. Lung and oropharyngeal depositions were measured by gamma scintigraphy. The mean percentage of the metered dose deposited in the lungs was 23.0% (SD 8.3%) for the Spacehaler and 12.8% (SD 6.8%) for the MDI (P < 0.01). However, there was no significant difference in the distribution patterns within the lungs between the two devices. Oropharyngeal deposition was significantly lower (P < 0.01) for the Spacehaler than for the MDI [mean (SD) 27.9% (16.4%) and 73.6% (8.7%), respectively] whilst the percentage of the metered dose remaining on the Spacehaler actuator was significantly greater than that on the MDI actuator [mean (SD) 48.0% (11.8%) and 12.4% (8.5%) respectively, P < 0.01]. There was evidence from the inhalation recordings that some patients experienced the 'cold Freon effect' whilst using the metered dose inhaler which may have contributed to the lower lung deposition seen with this device. This study demonstrates that the proportion of a 250 micrograms dose of beclomethasone dipropionate that is delivered to the lungs is significantly greater with the Spacehaler than the MDI. The Spacehaler also reduces the proportion of the does that is deposited in the oropharynx to less than half that observed with the MDI, and reduces the total dose of drug received by the patient.

Topics: Administration, Inhalation; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers

Hydrofluoroalkane-134a (HFA-134a) is a new chlorofluorocarbon (CFC)-free propellant for use in metered dose inhalers. It provides a more environmentally friendly alternative to CFC propellants because it does not contain chlorine which is responsible for ozone depletion by CFCs. Beclomethasone dipropionate (BDP) is widely used for inhalation asthma therapy and is most commonly delivered by a CFC propellant system. The present study evaluated the acute safety of BDP formulated with the new propellant (HFA-134a BDP) compared with BDP in a CFC-11/12 formulation by measuring the acute bronchial response in asthmatic patients. The study was conducted as a randomized, single-blind, placebo-controlled, four-period cross-over trial. Asthmatic patients received eight inhalations of four treatment regimens (HFA-134a BDP, 1600 mg total dose; CFC-11/12 BDP, 2000 mg total dose; HFA-134a placebo and CFC-11/12 placebo) in random order over four study days. Forced expired volume in 1 s (FEV1) was measured before and 2, 10, 20, 40 and 60 min after inhalation of the study treatments. The number of coughs was counted from the start of the first inhalation to 60 s after the last inhalation. There were no statistically significant differences between the treatment groups for changes in FEV1, for the number of coughs or for the occurrence or severity of bronchoconstriction. In asthmatic patients withholding bronchodilators, the new HFA-134a BDP propellant system proved as safe and was as well tolerated as the current CFC-11/12 BDP system. The two propellant systems without active drug were also equally well tolerated.

Topics: Administration, Topical; Adult; Aerosol Propellants; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Cross-Over Studies; Drug Evaluation; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Single-Blind Method

As part of a development programme for a range of new CFC-free beclomethasone dipropionate (BDP) inhalers, two multicentre double-blind studies have been conducted to compare the therapeutic equivalence of a new HFA-134a propellant-formulated BDP metered-dose inhaler (Norton Healthcare Ltd, London, U.K.) with a CFC counterpart for the management of adult patients with all grades of asthma. Doses of 100 micrograms qds for 6 weeks were administered in a low dose study and in a high dose study 500 micrograms qds doses were given for 12 weeks. Efficacy assessments included lung function (FEV1) in the clinic and asthma symptoms, peak flow rates and bronchodilator use by patients on diary cards. Safety parameters measured included routine haematology and biochemistry (including serum cortisols), clinical adverse events and throat swabs for Candida spp. Both CFC and HFA-formulations of inhaled BDP produced similar and significant improvements in lung function and asthma symptoms. In the low dose study, baseline to endpoint FEV1 increased from 2.2 +/- 0.51 to 2.5 +/- 0.81 (P = 0.0001) with BDP-CFC and from 2.2 +/- 0.51 to 2.6 +/- 0.81 with BDP-HFA (P = 0.0001), with no significant difference between treatments. In the high dose study, corresponding increases were 2.1 +/- 0.71 to 2.4 +/- 0.91 (P = 0.0002) for BDP-CFC and 2.1 +/- 0.71 to 2.3 +/- 0.71 (P = 0.017) for BDP-HFA. PEF also improved similarly on both treatments in both studies. Both formulations were well tolerated with no difference in the pattern of adverse events, effect on serum cortisol or Candida colonization. These studies showed that, in the management of asthma, the new HFA-formulated BDP metered dose inhaler is equivalent to, and directly substitutable for, the older CFC-formulated product at the same dose, making change-over for patients straightforward.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome

Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects.. To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily.. Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication.. After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications.. These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Reference Values; Triamcinolone Acetonide; Volunteers

A total of 132 adult asthmatics who were symptomatic on 500 microg x day(-1) inhaled beclomethasone dipropionate (BDP) were studied in an open-label randomized, parallel group, 12 week, clinical trial. The addition of 12 microg formoterol fumarate solution aerosol (pressurized metered dose inhaler) b.i.d. to BDP at a dose of 500 microg x day(-1) was compared with a higher dose of 1,000 microg x day(-1) BDP. Mean morning premedication peak expiratory flow rate (PEF) during the final week of treatment (primary end-point) increased in both groups compared to baseline. The estimated treatment difference of 20.4 L x min(-1) (95% confidence interval 3.2-37.6) after 12 weeks of treatment was statistically significant (p<0.05) in favour of the formoterol/BDP group. The overall mean morning premedication PEF for the entire treatment period was higher in the formotero/BDP group (p=0.002). The overall number of puffs of rescue medication and asthma symptom scores were less in the formotero/BDP group (p<0.01). Safety and tolerability evaluations were satisfactory in both groups. In conclusion, the results suggest that the addition of formoterol fumarate to the existing dose of an inhaled corticosteroid should be considered as an alternative to increasing the dose of inhaled corticosteroid in the inadequately controlled asthmatic.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Drug Therapy, Combination; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Retrospective Studies; Safety; Treatment Outcome

To compare the effect of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP; 400 microg/d) with that of chlorofluorocarbon (CFC) BDP (800 microg/d) on asthma health-related quality of life in a 12-week, parallel-group, multicenter study.. HFA-BDP is a new CFC-free preparation of BDP, which was developed as a result of CFCs being phased out from metered dose inhalers.. Following 7 to 12 days of prednisone, 30 mg/d, 347 adults with moderate asthma were randomized to receive either 400 microg/d HFA-BDP, 800 microg/d CFC-BDP, or HFA placebo for 12 weeks (all other oral and inhaled steroids were withdrawn). Patients completed the Asthma Quality of Life Questionnaire (AQLQ), and clinical asthma status was measured at the end of a run-in period, at randomization (after oral steroid treatment), and at the end of the study treatment.. Sixty-one patients withdrew, 43 due to worsening asthma (33 placebo; 5 HFA-BDP; 5 CFC-BDP). There was a deterioration in the AQLQ score (- 0.81) in the placebo group, and the difference between this and the stability observed in both the HFA-BDP group (+ 0.13) and the CFC-BDP group (- 0.03) was statistically significant (p

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Asthma; Beclomethasone; Chlorofluorocarbons; Drug Combinations; Female; Forced Expiratory Volume; Health Status; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Quality of Life; Safety; Surveys and Questionnaires; Treatment Outcome

Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Allergens; Asthma; Beclomethasone; Blood Proteins; Bronchial Provocation Tests; Double-Blind Method; Drug Therapy, Combination; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Platelet Activating Factor; Reactive Oxygen Species; Respiratory Burst; Ribonucleases; Salmeterol Xinafoate; Treatment Outcome; Zymosan

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides

It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.

Topics: Administration, Inhalation; Adult; Allergens; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Cross-Over Studies; Cyclooxygenase Inhibitors; Double-Blind Method; Forced Expiratory Volume; Glucocorticoids; Humans; Hypersensitivity, Immediate; Mass Spectrometry; Methacholine Chloride; Middle Aged; Oxidative Stress; Prostaglandins F; Reactive Oxygen Species; Skin Tests

A double-blind, randomized, parallel-group pilot study compared the relative efficacy of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP [QVAR]; mass median aerodynamic diameter, 0. 8-1.2 m) versus cholorofluorocarbon-11/12 BDP (CFC-BDP [Beclovent]; mass median aerodynamic diameter, 3.5-4.0 m) in 31 steroid naive patients with mild to moderate asthma (PC(20,) 4 mg/mL). Functional high-resolution computed tomography was used to assess the relative efficacy of HFA-BDP and CFC-BDP on regional air trapping, as an indirect measure of small airways function and on regional hyperreactivity. Pretreatment functional computed tomography was performed at residual volume before and after methacholine challenge. After 4 weeks of treatment, functional imaging was repeated before and after the same concentration of methacholine that was administered before the treatment (n = 19 patients). Quantitative assessment of changes in distribution of lung attenuation was performed. After 4 weeks of treatment, the HFA-BDP group showed significantly more improvement in air trapping overall (a shift in the lung attenuation curve at residual volume toward more attenuation) on the posttreatment computed tomography scan (P <.05; Fisher's Exact Test). After an equal constrictor stimulus (methacholine concentration), subjects treated with HFA-BDP (n = 10 patients) showed less increase in air trapping overall than subjects treated with CFC-BDP (n = 9 patients) on the posttreatment scans compared with the pretreatment scans (P <.001; Fisher's Exact Test). No significant difference was demonstrated between the 2 treatment groups with respect to improvement in symptoms, spirometry, or methacholine responsiveness assessed by FEV(1), except for a greater reduction in breathlessness in the HFA-BDP group (P <.05). We conclude that HFA-BDP may have greater efficacy in the peripheral airways and that this effect is better assessed with functional imaging computed tomography techniques than with conventional physiologic tests.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Asthma; Beclomethasone; Bronchial Provocation Tests; Chlorofluorocarbons; Double-Blind Method; Female; Humans; Hydrocarbons, Fluorinated; Image Processing, Computer-Assisted; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Pilot Projects; Respiratory Function Tests; Spirometry; Tomography Scanners, X-Ray Computed

Leukotrienes are bronchoactive mediators secreted by inflammatory cells in the respiratory mucosa on exposure to asthma triggers.. We investigated the effect of montelukast, a leukotriene receptor antagonist, on the release of leukotrienes in the respiratory mucosa of children with persistent asthma.. Twenty-three children aged 6 to 11 years with moderately severe asthma were treated in a cross-over design starting, after a 2-week run in period, with either montelukast (n = 12) or cromolyn (n = 11) for 4 weeks with a 2-week washout period between treatments. Twelve of them were then treated with either montelukast or beclomethasone for 6 months. The use of beta(2)-agonists was recorded on a diary card. The concentration of leukotriene C(4) (LTC(4)) was measured by HPLC in nasal washes obtained before and at the end of each treatment period. Eosinophilic cationic protein (ECP) was measured in the nasal washes by RIA.. The LTC(4) concentration significantly decreased in the children treated for the first 4 weeks with montelukast, from 5.03 +/- 1.17 to 1.42 +/- 0.33 ng/mL (P <.005), and a nonsignificant increase was noted in children treated with cromolyn, from 3.37 +/- 1.11 to 5.88 +/- 2.17 ng/mL (P =.17). ECP concentration also decreased in the children receiving montelukast (P =.12). The concentration of LTC(4) remained low after 3 and 6 months of treatment with montelukast (0.8 +/- 0.7 and 1.0 +/- 0.3 microg/mL) and was lower than with beclomethasone. Children treated with montelukast required significantly fewer beta(2)-agonists (P <.04),. Montelukast reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma parallel to reduction in ECP and clinical improvement. This effect was not observed when the same children were treated with cromolyn.

Topics: Acetates; Asthma; Beclomethasone; Blood Proteins; Child; Cromolyn Sodium; Cross-Over Studies; Cyclopropanes; Eosinophil Granule Proteins; Female; Humans; Inflammation Mediators; Leukotriene Antagonists; Leukotrienes; Male; Quinolines; Respiratory System; Ribonucleases; Sulfides

This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate (BDP) formulated in hydrofluoroalkane-134a (HFA-BDP) and the standard chlorofluorocarbon propellants (CFC-BDP). Because HFA-BDP has improved lung deposition compared with CFC-BDP, this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP.. In this multicenter, randomized, parallel-group blinded study, asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were randomized to receive one of 6 possible treatments: 100 microg/d, 400 microg/d, or 800 microg/d of HFA-BDP or 100 microg/d, 400 microg/d, or 800 microg/d of CFC-BDP for 6 weeks. Changes in spirometry, daytime asthma symptom and nighttime asthma-related sleep disturbance scores, morning and evening peak expiratory flows, and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment.. Three hundred twenty-three patients were randomized to the 6 treatment groups, which had similar demographics and baseline lung function. There were significantly larger changes from baseline at week 6 in FEV(1) percent predicted with increasing doses of both HFA-BDP and CFC-BDP. The FEV(1) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP. By using the Finney bioassay method, it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1) percent predicted as HFA-BDP (95% confidence interval, 1.1-11.6). All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well. Ten (17%) of 59 patients in this group reported an acute asthma episode, increased asthma symptoms (6 of the 8 reports of increased asthma symptoms were classified as severe), or both, and 8 patients withdrew from the study (3 for adverse events related to asthma).. Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control. Moreover, the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Safety

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Forced Expiratory Volume; Humans; Male; Medical Records; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

We have compared the serum pharmacokinetics of the metabolites of beclomethasone dipropionate after inhalation from chlorofluorocarbon (CFC) and hydrofluoroalkane HFA-134a (HFA) formulations in asthmatic patients. Twenty-three patients completed this open-label, randomized, single-dose, three-period crossover study. Each patient received in separate periods 200 microg or 400 microg HFA-beclomethasone dipropionate, or 400 microg CFC-beclomethasone dipropionate. Venous blood samples were collected over 24 h for the determination of beclomethasone esters and beclomethasone in the serum. Significant differences in pharmacokinetics following HFA- and CFC-beclomethasone dipropionate were observed. Following a 400 microg beclomethasone dipropionate dose, the HFA formulation gave mean maximum concentrations (Cmax) and area under the curve (AUC) values of beclomethasone esters of 1153 pg mL(-1) and 4328 pg h mL(-1), respectively, and beclomethasone Cmax and AUC values of 69 pg mL(-1) and 682 pg h mL(-1), respectively. These values were approximately 2-3-fold those seen with the CFC formulation (beclomethasone esters Cmax and AUC of 380 pg mL(-1) and 1764 pg h mL(-1), respectively; beclomethasone Cmax and AUC of 41 pg ml(-1) and 366 pg h mL(-1), respectively). Beclomethasone esters, the major component of beclomethasone dipropionate in the serum, peaked significantly earlier for the HFA formulation (0.8 h) than for the CFC formulation (2 h). Tests for dose proportionality of beclomethasone esters pharmacokinetics following HFA-beclomethasone dipropionate showed that the two hydrofluoroalkane strengths were proportional. The more rapid and greater efficiency of systemic drug delivery of the HFA formulation compared with the CFC formulation can be explained if most of each inhalation from CFC-beclomethasone dipropionate is swallowed and absorbed orally, whereas most of each inhalation from HFA-beclomethasone dipropionate is absorbed through the lungs. There is a need for comprehensive dose-response efficacy trials, with the use of the steep portion of the dose-response relationship, to evaluate the significance of these pharmacokinetic differences.

Topics: Adult; Anti-Asthmatic Agents; Area Under Curve; Asthma; Beclomethasone; Chlorofluorocarbons; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Single-Blind Method

Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

In order to compare the efficacy of different asthma treatment in subjects with mild-to-moderate asthma, three groups of 11 patients were treated with nedocromil sodium (NS), beclomethasone dipropionate (BDP) and beclomethasone dipropionate plus salmeterol (BDP + S) in an open, randomized study. Symptom score, peak expiratory flow (PEF) maximal amplitude, forced expiratory volume in one second (FEV1), and methacholine reactivity were measured at the baseline and at intervals of 3 months up to 12 months. After 3 months, symptoms reduced significantly in all treatment groups, while PEF variability improved in BDP and BDP + S groups; FEV1 and bronchial responsiveness to methacholine were significantly improved in comparison with baseline value in the BDP + S group only. No significant difference was observed after 6 and 12 months of treatment in PEF variability, FEV1 or bronchial hyperreactivity in the NS group compared with baseline values, while a significant difference was observed in symptom score. BDP group showed a significant improvement in FEV1 and bronchial reactivity to methacholine after 6 and 12 months of treatment. In the BDP + S group, the improvement in symptoms and pulmonary function persisted until the end of the study. In conclusion, the combination of beclomethasone dipropionate and salmeterol improved pulmonary function and bronchial reactivity earlier than beclomethasone dipropionate alone, while nedocromil sodium improved symptoms but not pulmonary function. Assuming that bronchial reactivity could be an indirect measurement of airway inflammation, overtreatment of asthma in relationship with the classification of asthma severity of the International Guidelines could improve both airway inflammation and the prognosis of airway obstruction.

Topics: Adolescent; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Middle Aged; Nedocromil; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Time Factors

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Remodeling; Child; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Male; Prospective Studies

Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma.. We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray.. A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements.. Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed.. Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.

Topics: Adolescent; Adult; Aerosols; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Middle Aged; Spirometry; Theophylline

The efficacy and safety of regular-strength beclomethasone dipropionate MDI prescribed within its recommended dosing range of 2 to 5 puffs three to four times daily has been well established in more than 25 years of worldwide use. A more concentrated formulation delivering 84 microg per puff was developed to provide for a more convenient twice-daily dosing regimen.. This randomized, single-blinded, positive and placebo-controlled, parallel-group, multiple-dose bioactivity study was conducted to assess the potential of a new beclomethasone dipropionate 84 microg double-strength metered-dose inhaler (Vanceril 84 microg Double Strength Inhalation Aerosol/Key) to cause hypothalamic-pituitary-adrenocortical axis suppression.. Beclomethasone dipropionate double-strength 84 microg was compared with beclomethasone dipropionate regular-strength 42 microg, orally administered prednisone, and placebo inhaler after 36 consecutive days of administration in adults with moderate asthma. Beclomethasone dipropionate double-strength was administered as 5 puffs BID and beclomethasone dipropionate regular-strength was administered as 10 puffs BID for the same total daily dose of 840 microg of beclomethasone dipropionate. Oral prednisone was administered by mouth at 10 mg once a day. The potential for hypothalamic-pituitary-adrenocortical axis suppression was evaluated by an adrenocorticotropic hormone (ACTH) stimulation test using cosyntropin 250 microg in 500 mL normal saline infused over six hours on the 36th day of treatment. Sixty-four patients completed this study.. No clinically significant post-study findings were observed from physical examination, electrocardiogram, or clinical laboratory evaluation for any treatment group. No serious or unexpected adverse events were reported. On the 36th day of treatment, there was a significant (P < .01) difference in the plasma cortisol concentration response to cosyntropin stimulation between the prednisone and placebo treatment groups at the sixth hour of infusion. There was no significant difference in the plasma cortisol concentration response to cosyntropin stimulation between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength treatment groups and the placebo group. In addition, comparison of the response between the beclomethasone dipropionate double-strength and beclomethasone dipropionate regular-strength groups showed no significant difference.. Beclomethasone dipropionate, administered either via a double-strength (84 microg/puff) or regular-strength (42 microg/puff) inhaler dosed at 840 microg/day showed no evidence of hypothalamic-pituitary-adrenocortical axis suppression in adults with moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone; Adult; Asthma; Beclomethasone; Cosyntropin; Drug Evaluation; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisone; Safety; Single-Blind Method

Results from previous investigations that examined the psychological side effects of theophylline have been inconsistent, and none have reported about inhaled corticosteroids. The objective of this study was to assess the relative psychological side effects of theophylline and beclomethasone in asthmatic children.. This was a multicenter, randomized, double-blind, parallel-groups study in which 102 asthmatic patients were assigned to one of two treatments: beclomethasone three times daily or theophylline twice daily. At baseline, 1 month, and 1 year, parents completed standardized behavioral questionnaires while the children received psychometric testing of attention and concentration, memory and learning, and problem-solving.. Although power was sufficient to detect meaningful mean score changes, no consistent differential treatment effects were observed. Two significant treatment-by-period interactions were discordant, with one suggesting slightly better attention in the theophylline group, whereas the other indicated a small advantage in attention scores in the beclomethasone group. Numerous significant period effects revealed that behavior and cognitive test performance improved over the 1-year period, regardless of treatment, and confirmed a well established practice effect resulting from repeated administrations of such tests.. Neither theophylline nor beclomethasone should be avoided out of concern for significant psychological side effects. The possibility remains that a subset of asthmatic children may be susceptible to such medication-induced changes; investigators have suggested that preschool children may be at particular risk, although no controlled studies with this age group have been conducted. Parental perceptions of medication side effects can be influenced by temporary effects present at initiation of treatment or by erroneous attribution of the psychological effects of the chronic illness. Reports of psychological changes in response to asthma medications must be addressed respectfully but objectively, with due consideration of available evidence and an awareness of other potential explanations.

Topics: Administration, Inhalation; Adolescent; Adolescent Behavior; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child Behavior Disorders; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Psychology, Adolescent; Psychology, Child; Psychometrics; Theophylline

We investigated the effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor antagonist, in 11 patients with severe bronchial asthma. The patients had been treated with 1600 micrograms/day of beclomethasone or 800-1600 micrograms/day of beclomethasone plus 2.5-20 mg/day of prednisolone, but remained symptomatic. After a 2-week baseline period, the patients received 225 mg of pranlukast twice daily for 8 weeks. Morning and evening peak expiratory flow rate (PEF) and symptom scores (cough, dyspnea, sleep) were recorded in an asthma diary. Ten patients completed the study. Symptom scores, especially dyspnea and sleep scores, and the number of rescue beta 2-agonist inhalations were significantly decreased. The morning PEF significantly improved from a mean baseline value of 311 to 341 L/min by the end of the study period. The evening PEF also improved, from 328 to 348 L/min, although the difference was not significant. These results suggest that pranlukast may be effective in treating patients with severe asthma who are refractory to corticosteroid therapy.

Topics: Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chromones; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Prednisolone

There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.

Topics: Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Belgium; Bone Density; Bronchodilator Agents; Budesonide; Calcium; Cross-Over Studies; Double-Blind Method; Female; Femur Neck; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hydroxyproline; Male; Middle Aged; Osteocalcin; Peak Expiratory Flow Rate; Safety; Salmeterol Xinafoate; Spine

To investigate growth and markers of collagen and bone metabolism in prepubertal children with asthma.. We measured growth velocity over 12 months and markers of collagen types I and III synthesis (PINP, PICP, PIIINP), collagen type I degradation (ICTP), and bone metabolism (bone-specific alkaline phosphatase and osteocalcin) on one occasion in 56 prepubertal children with stable asthma, 39 of whom were treated with inhaled budesonide or beclomethasone. Collagen data were compared with normal control values.. Children treated with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with control subjects (p = 0.038, p = 0.045), although PICP was increased (p = 0.05). Carboxyterminal telopeptide of type I collagen was reduced in patients treated with inhaled steroids (p < 0.0005) compared with nonsteroid-treated patients. Serum osteocalcin but not bone-specific alkaline phosphatase was significantly reduced in children treated with inhaled steroids (p < 0.02). Significant correlation was observed between PIIINP and ICTP and growth velocity.. Collagen turnover is reduced in children with asthma receiving long-term inhaled steroid treatment. Markers of collagen synthesis provide a more accurate reflection of growth disturbance than osteocalcin and bone-specific alkaline phosphatase.

Topics: Administration, Inhalation; Alkaline Phosphatase; Asthma; Beclomethasone; Bone and Bones; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Collagen; Female; Glucocorticoids; Growth; Humans; Male; Osteocalcin

At this time, no placebo-controlled studies in the clinical literature compare the efficacy and safety of the most widely prescribed oral inhaled corticosteroids when dosed at their recommended daily doses. This study compared the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide (TA) 800 microg/day by MDI with a built-in tube extender in adults with persistent asthma.. This 56-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter trial was conducted in 328 adults with mild to moderately severe asthma (FEV1 50% to 90% of predicted while maintained on inhaled corticosteroids). Patients were seen at a baseline visit and on study days 28 and 56. Efficacy variables included pulmonary function tests, physician and patient assessments of asthma condition, and use of rescue medication.. Statistically significant improvements from baseline in most efficacy measures were demonstrated for both active treatments versus placebo, and with the following exception were the same between active treatments: mean increase in FEV1 in the beclomethasone dipropionate group was statistically significantly greater than in the triamcinolone acetonide group on day 28. Throughout the study, BDP was statistically superior to TA with respect to mean change from baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean average weekly use of rescue albuterol (the two active treatments were comparable for this variable at all other time points). Beclomethasone dipropionate and TA were comparable in safety.. In adult patients with mild to moderately severe persistent asthma, treatment with BDP consistently conferred greater improvement from baseline in mean FEV1 than TA. This difference achieved statistical significance after 28 days of therapy but was not maintained to endpoint. Decreases in overall asthma symptom scores and in the use of rescue albuterol were statistically significantly greater for the BDP group compared with the TA group. Based on these findings, we conclude that BDP is at least as effective as TA in the treatment of persistent asthma in adults, and judged by some measures, may be superior.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Triamcinolone Acetonide

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bone Density; Budesonide; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Pilot Projects

The growth of 50 children receiving regular inhaled corticosteroids was segregated into divisions of six weeks from the start of treatment and compared with their growth when not receiving regular corticosteroids using a random effects regression model. Growth suppression was most marked during the initial six weeks after starting treatment, with most suppression occurring during the initial 18 weeks. Thereafter the children's growth was similar to their growth when not receiving treatment. These findings have important consequences for patterns of treatment of asthma in children.

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Growth; Humans; Longitudinal Studies; Regression Analysis; Time Factors

To determine the ability of budesonide via an inhaler (Pulmicort Turbuhaler; Astra Draco AB) to replace oral glucocorticosteroids (GCSs) in adult subjects with moderate-to-severe asthma.. Double-blind, randomized, and placebo-controlled study, with parallel groups.. Multicenter study in outpatient setting.. Eighty men and 79 women, aged 20 to 69 years, with moderate-to-severe asthma and a mean FEV1 of 58.3% predicted normal. All subjects were receiving oral GCS treatment and 79% of subjects were also receiving inhaled beclomethasone dipropionate (BDP). The mean daily doses of prednisone at baseline, including converted dose of BDP, for the placebo, budesonide 400 microg, and budesonide 800 microg, respectively, were 19.7 mg, 19.5 mg, and 18.7 mg.. After a 2-week baseline period, subjects entered a 20-week treatment period, during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals.. Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction (82.9% and 79.0% respectively) in oral GCS dose compared with placebo-treated subjects (27%; p<0.001). Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation, compared with 8% in the placebo group. Additionally, both doses of budesonide resulted in significant improvement in results of pulmonary function tests and asthma symptoms scores, and a significant decrease in the use of bronchodilator therapy. The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects.. Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Prednisone; Respiratory Function Tests

Clodronate is a novel drug used for inhibiting osteoclastic activity. The aim of the present double-blind study was to evaluate the efficacy and tolerability of clodronate (Leiras, Finland) in corticosteroid-induced bone loss among asthmatic patients. Seventy-four adult patients (41 women and 33 men, mean age 57.3 years) having a long history (mean 8.1 years) of oral and inhaled corticosteroid therapy were randomized to four parallel treatment groups: clodronate 800, 1600, or 2400 mg/day, or an identical placebo. The bone mineral density (BMD) of the lumbar spine (L2-4), femoral neck, and trochanter were assessed using dual-energy X-ray absortiometry at entry, 6 months, and 12 months. The baseline BMDs did not differ significantly between the study groups. In the lumbar spine, the mean BMD increased significantly between the baseline and 12-month visit in the clodronate groups of 1600 and 2400 mg/day, 2.6% (0.02 g/cm2, p < 0.02) and 3.0% (0.03 g/cm2, p < 0.01), respectively, but not in the placebo and clodronate 800 mg/day groups. The test for a linear trend (BMD percent change for L2-4) at 12 months was significant (p < 0.02), indicating a dose response to clodronate. The mean BMD values of the femoral neck increased significantly in the 2400 mg/day group, 4.3% (0.03 g/cm2, p < 0.0001), as well as in the trochanter region 2.8% (0.02 g/cm2, p < 0.02). Gastric irritation was the most common adverse effect noted on a clodronate dose of 2400 mg/day. We conclude that oral clodronate is effective in preventing bone loss or increasing bone mass in asthmatic patients having a long history of continuous peroral and inhaled corticosteroid administration.

Topics: Absorptiometry, Photon; Administration, Inhalation; Administration, Oral; Analgesics, Non-Narcotic; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Clodronic Acid; Dose-Response Relationship, Drug; Double-Blind Method; Female; Femur; Femur Neck; Glucocorticoids; Humans; Lumbar Vertebrae; Male; Osteoporosis; Prednisolone

Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective in modifying airway inflammation. However, there is not much data on the effects of corticosteroid-treatment on the basement membrane.. To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the bronchial mucosa, and the expression of growth factors in patients with asthma.. We studied bronchial biopsies from 24 asthmatic patients before and after treatment with inhaled BDP, 400 microg twice a day or placebo, for 6 months in a double-blind manner. Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expression of growth factors were examined by immunohistochemistry in endobronchial biopsy specimens.. After 6 months of treatment, we observed a significant improvement of asthma symptoms (P<0.01), PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P< 0.05) in the BDP group compared with the placebo group. This was accompanied by a significant decrease in the thickness of the lamina reticularis (P < 0.001), and in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant correlation was found between the IGF-I expression and collagen thickening (rs = 0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01).. These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Basement Membrane; Beclomethasone; Bronchi; Bronchoscopy; Double-Blind Method; Forced Expiratory Volume; Humans; Inflammation; Insulin-Like Growth Factor I; Microscopy, Electron; Middle Aged; Mucous Membrane; Peak Expiratory Flow Rate

Topics: Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; History, 20th Century; Humans; Theophylline

Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 microg twice daily (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 microg twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication.

Topics: Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Respiratory Function Tests; Salmeterol Xinafoate; Statistics, Nonparametric; Treatment Outcome

The effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation have not yet been examined. We therefore, compared the effects of inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control outcomes and markers of airway inflammation. Twenty-four adult subjects with mild and moderate asthma were randomized to receive either BDP or placebo for four weeks; then subjects entered a single blind four week placebo run-in period. We found that the BDP group had significantly greater improvements in forced expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol use than the placebo-treated group. The improvement in FEV1 largely reversed one week after treatment was stopped. The decrease in the median percentage of eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not significant, but because eosinophils increased from 8.4% to 12.7% in the placebo group, there was a significant difference between treatment groups (p=0.03). There was no significant difference between groups during treatment in the levels of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or fibrinogen in induced sputum. The change in FEV1 in the BDP group did not correlate significantly with the change in eosinophil percentage or ECP levels. We concluded that four weeks of treatment with inhaled beclomethasone dipropionate 336 microg x day(-1) was associated with significant improvements in peak flow, forced expiratory volume in one second, and rescue salbutamol use in asthmatic subjects but was not associated with large reductions in markers of eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.

Topics: Administration, Inhalation; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Bronchial Provocation Tests; Bronchodilator Agents; Cell Count; Chymases; Double-Blind Method; Eosinophil Granule Proteins; Female; Fibrinogen; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation Mediators; Male; Maximal Midexpiratory Flow Rate; Mucins; Ribonucleases; Serine Endopeptidases; Single-Blind Method; Spirometry; Sputum; Tryptases

Bronchial inflammation plays a central role in asthma. We investigated whether parameters of inflammation were increased in peripheral blood. Furthermore, we tested whether fluticasone propionate (FP), a new inhaled corticosteroid (ICS), and beclomethasone dipropionate (BDP) affected these parameters. FP 750 microg/day and BDP 1500 microg/day were compared in a randomized, crossover study consisting of two 6-week treatment periods, each preceded by a 3-week placebo period. Twenty-one patients with symptomatic asthma completed the study. The results were compared with those of six normal subjects (controls). Immunophenotyping of inflammatory cells was performed in whole blood, and serum eosinophil cationic protein (ECP) was measured. With regard to clinical efficacy, ICS increased PC20 histamine by more than 1.9 doubling doses and FEV1 by more than 0.34 l. The number of CD3/HLA-DR+ lymphocytes was significantly increased in asthmatics compared to the normal subjects, both after placebo (P<0.01) and after therapy (P<0.05). The CD3/HLA-DR+ lymphocytes decreased significantly after treatment with FP (P<0.05). Serum ECP was elevated in patients without ICS and decreased after treatment with BDP (P<0.001). In conclusion, the number of CD3/HLA-DR+ lymphocytes and serum ECP levels were raised in the peripheral blood of symptomatic asthmatics, and decreased by clinically effective doses of ICS. In this respect, FP 750 microg/day was at least as effective as BDP 1500 microg/day.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; CD3 Complex; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Flow Cytometry; Fluticasone; HLA-DR Antigens; Humans; Leukocyte Common Antigens; Male; Middle Aged; Phenotype; Receptors, Interleukin-2; T-Lymphocytes

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from suppressed bone formation may therefore contribute to glucocorticoid-associated bone loss in asthma. Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG. Although the effects of high-dose IG on BMD are associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Beclomethasone; Biomarkers; Bone Density; Budesonide; Dehydroepiandrosterone Sulfate; Female; Femur; Glucocorticoids; Humans; Hydrocortisone; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Ribs

Patient evaluation of asthma severity and medication needs is mostly based on respiratory symptoms and may be influenced by changes in perception of bronchoconstriction-induced sensations. However, the influence of asthma medication on the ability to perceive symptoms is still to be documented. This study evaluated the effects of short-term and regular use of salmeterol on the perception of methacholine-induced bronchoconstriction (MIB) in subjects with mild asthma, using inhaled salbutamol on an "as required" basis (n=15), and in subjects with moderate asthma, using daily inhaled beclomethasone (mean daily dose, 640 microg; n=15) in addition to salbutamol to control their asthma.. Methacholine challenges (MC) were performed at entry into the study, and then before, 1, and 12 h following inhalation of 50 microg of salmeterol or a placebo, after a 15-day baseline period; and after 4 weeks of twice daily use of those treatments. The measurements were then repeated with the alternate treatment after a 15-day washout period. Finally, a last MC was performed after another 15-day washout period. For each MC, the perception score of bronchoconstriction-associated breathlessness at 20% fall in FEV1 (PS20) was evaluated on a modified Borg scale from 0 to 10.. Subjects using regular beclomethasone had a higher baseline PS20 than those using only salbutamol (means: 3.06 0.06 and 2.01+/-0.07, p=0.0001). Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid). Although there were some intraindividual variations, mean PS20 did not vary significantly throughout the study.. These observations show that the perception of bronchoconstriction-associated breathlessness is not influenced by regular use of salmeterol. Patients using inhaled corticosteroids show a greater perception of MIB.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Middle Aged; Perception; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome

The clinical efficacy, tolerability and acceptability of a new multidose powder inhaler (MDPI) containing beclomethasone dipropionate (BDP) were compared with those of a BDP aerosol administered with a large volume spacer (MDI-spacer) among adult asthmatics currently receiving from 500 to 1,000 microgram/day of an inhaled corticosteroid. During the study, the dosage of BDP from both devices was 400 microgram twice daily. Ninety-one patients were randomized to the MDPI group and 42 to the MDI-spacer group. The trial was performed as an open, randomized, parallel group multicenter study. The duration of the treatment period was 12 weeks, and the study was preceded by a 2-week run-in period. During the run-in period, the mean morning peak expiratory flow (PEF) was 487 and 466 1/min in the MDPI and MDI-spacer groups, respectively. After the 12-week treatment, the morning PEF was 491 1/min in the MDPI group and 463 1/min in the MDI-spacer group. The evening values were 500 and 479 1/min during the run-in period and 496 and 476 1/min after the 12-week treatment, respectively. Asthma symptom scores and the use of rescue medication were low in both groups, indicating good efficacy of the preparations tested. The median dose of histamine required to decrease forced expiratory volume in 1 s by 15% increased during the study from 800 to 1,098 microgram in the MDPI group and from 795 to 960 microgram in the MDI-spacer group. The most frequent adverse events in both groups were hoarseness and sore throat. There were no statistically significant differences between the treatment groups in serum cortisol values or in the number of patients with thrush. Seventy-two percent of the patients regarded the MDPI easier to use while 95% considered it more portable. Over 80% of the patients felt that the MDPI was also easier to clean and as easy or easier to learn to use than the MDI-spacer. To conclude, the novel powder inhaler is well tolerated and at least equally effective as the conventional MDI-spacer combination in the treatment of asthma with BDP. However, in everyday use, patients clearly favored the powder inhaler.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Confidence Intervals; Dose-Response Relationship, Drug; Female; Finland; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Statistics, Nonparametric; Treatment Outcome

We hypothesized that regular use of long-acting beta-agonists could delay recognition of ("mask") increasing airway inflammation. We studied steroid-sparing and "masking" effects of salmeterol versus placebo in 13 asthmatic individuals requiring >= 1,500 microgram inhaled corticosteroid daily. Corticosteroid doses were reduced weekly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternative treatment. Subjects maintained symptom and peak expiratory flow (PEF) diaries, and underwent weekly spirometric, methacholine challenge, sputum eosinophil, and serum eosinophil cationic protein (ECP) measurements. Mean corticosteroid dose was reduced by 87% during salmeterol treatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increased before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were higher in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], versus placebo 9.3 +/- 17.6%; p = 0.006). Five subjects showed > 10% sputum eosinophilia before exacerbation during salmeterol treatment, as compared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly more advanced. We conclude that the bronchodilating and symptom-relieving effects of salmeterol can mask increasing inflammation and delay awareness of worsening asthma.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Bronchial Provocation Tests; Bronchitis; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Disease Progression; Eosinophil Granule Proteins; Eosinophils; Female; Glucocorticoids; Humans; Inflammation Mediators; Leukocyte Count; Male; Methacholine Chloride; Middle Aged; Peak Expiratory Flow Rate; Placebos; Ribonucleases; Salmeterol Xinafoate; Spirometry; Sputum

The anti-asthmatic effect of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 micrograms/day. The trial was designed as a randomized, double-blind, parallel-group study in several European countries. 69 patients were treated for 6 weeks with theophylline plus BDP 400 micrograms/day, compared to 64 patients treated with BDP 800 micrograms/day. The mean +/- SD serum theophylline concentration was 10.1 +/- 4.2 mg/l. Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow rate (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p < 0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p < 0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 micrograms/day and beclomethasone dipropionate 800 micrograms/day in patients whose asthma is not controlled on beclomethasone dipropionate 400 micrograms/d. The results support the use of theophylline as steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.

Topics: Adolescent; Adult; Aged; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Europe; Forced Expiratory Volume; Humans; Middle Aged; Theophylline

In this study, the efficacy and safety of triamcinolone acetonide (TA) metered-dose inhaler with a built-in tube extender and beclomethasone dipropionate (BDP) metered-dose inhaler without a spacer device were compared. Both treatments were dosed at their most commonly used daily doses (within labeling).. A 56-day, randomized, double-blind, double-dummy, placebo-controlled trial.. Seventeen asthma/allergy centers.. We enrolled 339 patients 18 to 65 years of age, with a documented history of bronchial asthma (FEV1, 50 to 90% of predicted value) for > or = 2 years who required inhaled corticosteroid therapy.. Patients were randomized to receive BDP 336 microg/d (4 puffs bid) plus TA placebo (4 puffs bid), TA 800 microg/d (4 puffs bid) plus BDP placebo (4 puffs bid), or TA and BDP placebos (4 puffs of each bid). The only other asthma medication permitted was inhaled albuterol that was used as a rescue medication. All medications were administered via the closed-mouth inhalation technique.. At 8 weeks and at study end point, both active treatment groups had statistically significant and comparable improvements in FEV1 relative to baseline, and statistically significant increases relative to placebo. At study end point, improvements in forced expiratory flow (FEF25.75%), clinic peak expiratory flow (PEFR), and FVC were statistically significant for the active treatment groups compared with placebo. At end point, the mean difference between BDP and TA for mean change in FEV1 from baseline in the efficacy population was 0.02 and the 95% confidence interval was -0.11, 0.15. Asthma symptoms recorded at clinic visits showed statistically significant improvements for the BDP and TA groups compared with the placebo group. Treatment-related adverse events occurred with similar frequency in all patient groups-25.5% of placebo-treated patients, 22.3% of BDP patients, and 20.4% of TA patients. The incidence of oropharyngeal adverse events, including cough, thrush, and dysphonia, was not statistically different between the two active treatment groups.. In this randomized, double-blind, placebo-controlled study of adult asthmatics treated with either BDP without a spacer or TA with its built-in tube extender, BDP and TA were comparable in efficacy as measured by FEV1 and other pulmonary function tests, and by improvement in asthma symptoms. Both active treatments were significantly more effective than placebo. All treatment groups were comparable in safety as measured by the incidence of adverse events.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Triamcinolone Acetonide; Vital Capacity

The measurement of exhaled nitric oxide (ENO) is recognized as a marker of airway inflammation. ENO was measured in 10 nonsteroid-treated asthmatics at recruitment, during 3 weeks of inhaled beclomethasone (1000 microg/day) and for 3 weeks after withdrawal. Baseline ENO was increased in asthma compared with nonasthmatics (85.0+/-54.5 vs. 24.5+/-14.8 ppb, p < 0.0001). After inhaled steroid, there was no significant change in forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC), but methacholine PC20 rose significantly (p = 0.0345). ENO (mean+/-SD; % baseline) fell after 1 week on steroid to 60.6+/-31.1 and rose to 95.3+/-46.1 at 1 week after withdrawal. ENO did not correlate with PC20 or FEV1. The changes in ENO and PC20 were inversely correlated (r2 = 0.325). ENO may be an index of airway inflammation and therapeutic response in bronchial asthma.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Methacholine Chloride; Nitric Oxide; Vital Capacity

The study was undertaken to compare the efficacy and safety of beclomethasone dipropionate inhalation powder inhaled by Rotahaler (Becotide Rotacaps, Glaxo Wellcome) and by Cyclohaler (Beclomethasone Cyclocaps, Pharmachemie). Both the Cyclohaler and the Rotahaler are single-dose dry powder inhalation devices for inhalation capsules. 182 asthma patients stabilized on inhaled beclomethasone dipropionate 800 micrograms daily, were randomly assigned to treatment with 800 micrograms beclomethasone dipropionate inhaled by Rotahaler (91 patients) or Cyclohaler (91 patients) in a double-blind manner, using the double-dummy method. It was shown that the asthma remained stable during the 16-week study period with both preparations. There were no statistically significant differences in the pulmonary parameters (morning PEF, evening PEF, FEV1). The test/reference ratio of the morning PEF (99.5%, CI 93.0% - 106.5%) was well within the equivalence interval, which had been set a priori from 85% to 117.6%. There were no marked differences between the Cyclocaps and Rotacaps group in symptom scores and adverse events. A total of 12 patients had an asthma exacerbation: 8 exacerbations occurred in the Rotahaler group and 4 in the Cyclohaler group. The difference was not statistically significant. The use of rescue medication was somewhat higher in the Rotahaler group, but the difference did not reach statistical significance. Significantly more patients (17 patients) withdrew from the study in the Rotahaler group than in the Cyclohaler group (5 patients). In conclusion, there was no difference in asthma control of patients treated with Beclomethasone Cyclocaps inhaled by Cyclohaler and Becotide Rotacaps inhaled by Rotahaler. Both preparations are therapeutically equivalent.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests

To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.. Randomised, double blind, placebo controlled, crossover trial.. Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.. There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.. This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.

Topics: Acute Disease; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Child; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Lung; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Treatment Failure

Home peak expiratory flow (PEF) measurements have become the cornerstone of asthma self-management plans. However, the cut-off values for changing treatment have not been formally tested. This study focusses on the possible overtreatment brought about by the different cut-off values and denominators currently employed. Data from 133 clinically stable asthmatic patients from a 2.5 yr follow-up study were analysed. The results showed that strict adherence to current criteria would lead to severe overtreatment, with up to 30% of clinically stable patients crossing into the lowest (red) zone at least once a year when personal best is the denominator and when it has not been limited to a defined time of day or to defined prior bronchodilator use. As expected, the passage of clinically stable patients into the lower zones became less frequent when cut-off values were sharpened and when time- and treatment-specific PEFs were used as the denominators. Strict adherence to commonly used peak expiratory flow cut-off values would lead to considerable overtreatment. In order to avoid overtreatment, the morning peak expiratory flow before any (bronchodilator) treatment should be related to the personal best peak expiratory flow measured under the same conditions. The choice of the right cut-off value will also depend on studies being performed to test the amount of undertreatment with a given value.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Health Services Misuse; Humans; Ipratropium; Male; Middle Aged; Peak Expiratory Flow Rate; Prevalence; Prognosis; Risk Assessment; Self Administration; Terbutaline; Treatment Outcome

To investigate the adherence behaviors (MDI use, MDI/spacer technique, appointment attendance, smoking in the home) of low-income, urban, primarily African American children with asthma.. Participants were 55 children ages 6 to 17 with moderate to severe asthma. Adherence to MDI anti-inflammatory agents was estimated primarily from canister weight at the follow-up appointment.. The mean use of MDI medication was 44% of prescribed use, with 27% of subjects demonstrating MDI/spacer technique likely to prevent drug delivery. Almost half reported that household members smoked cigarettes, and 21% missed scheduled follow-up appointments.. These findings have implications for how clinicians should assess and improve adherence.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Black or African American; Black People; Child; Cromolyn Sodium; Female; Follow-Up Studies; Health Knowledge, Attitudes, Practice; Humans; Incidence; Male; Middle Aged; Nebulizers and Vaporizers; Nedocromil; Parent-Child Relations; Patient Compliance; Patient Education as Topic; Smoking; Social Class; Socioeconomic Factors; Triamcinolone Acetonide; United States

Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.. The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.. There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.. FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male

There is a dearth of data on long-term effects of inhaled corticosteroids (ICS) on bone architecture in childhood asthma. This study was designed to assess the possible effects of two different inhaled steroids on bone mineral density (BMD) in steroid-naïve, prepubertal children. Twenty-three children were randomized to receive equipotent doses of either fluticasone propionate (100 micrograms twice daily) or beclomethasone dipropionate (200 micrograms twice daily). They were followed up over a period of 20 months with regular dual-energy X-ray absorptiometry scans for BMD. Densitometry of lumbar spine and total body showed a significant increase over time, which followed the normal patterns for growth. No difference was observed between the two subgroups. There was no change in fat distribution over time and no increase in percentage total body fat. As expected, girls had significantly higher total body fat. This absence of deleterious effects suggests that in the standard doses used neither beclomethasone nor fluticasone has any significant effect on bone density over a moderate period of time. Further studies should continue monitoring BMD through the critical years of bone mass accumulation during adolescence.

Topics: Absorptiometry, Photon; Adipose Tissue; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone Density; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Lumbar Vertebrae; Male

The mandatory requirement to eliminate chlorofluorocarbons (CFCs) as propellants in pharmaceutical aerosols has provided the opportunity to enhance significantly the delivery of aerosol drugs to the respiratory tract. This randomized, parallel-group, double-blind, double-dummy, multicentre study was undertaken to assess whether beclomethasone dipropionate (BDP) in hydrofluoroalkane-134a (HFA) provided equivalent control of moderately severe asthma to BDP in CFC but at approximately half the total daily dose, as might be expected from the improved lung deposition of the HFA-BDP extrafine aerosol. The novel study design included a 10-12 day run-in period to confirm that patients met established criteria of moderately severe asthma and were symptomatic on current therapy (inhaled beta-agonist plus CFC-BDP 400-800 micrograms day-1). This run-in period was followed by a short course of oral steroid therapy (prednisolone 30 mg day-1 for 7-13 days) to demonstrate steroid responsiveness [> or = 15% improvement in morning peak expiratory flow (PEF)] and to provide a within-study baseline of improved asthma control. A total of 233 patients were randomized to treatment for 12 weeks with HFA-BDP 800 micrograms day-1 (116 patients) or CFC-BDP 1500 micrograms day-1 (117 patients). The mean change from oral steroid treatment in morning PEF with HFA-BDP was equivalent to that seen with CFC-BDP at all time intervals. Changes in other measures of pulmonary function, asthma symptom scores and beta-agonist use were equivalent in the two treatment groups throughout the 12 week treatment period. The safety profile of HFA-BDP compared favourably with that of CFC-BDP with no unexpected adverse events reported. Fewer patients on HFA-BDP than on CFC-BDP had plasma cortisol levels below the normal reference range after 12 weeks of therapy (5.1% vs. 17.3%, respectively). In conclusion, HFA-BDP extrafine aerosol was found to provide equivalent control of moderately severe asthma to CFC-BDP at approximately half the daily dose with a favourable safety profile, suggesting an improved therapeutic ratio.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aerosol Propellants; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Middle Aged

Herein we assess the safety of an inhaled formulation of beclomethasone dipropionate (BDP) which uses the propellant hydrofluoroalkane-134a (HFA) for the treatment of asthma. Acute local tolerability (as assessed by the incidence of cough and mean forced expiratory volume after 1 s inhalation) was similar for both BDP and placebo formulated in either chlorofluorocarbon (CFC) or HFA propellants. A total of 43 patients were treated with HFA-BDP (0, 200, 400 or 800 micrograms day-1) or CFC-BDP (800 micrograms day-1) for 14 days and their 24 h urinary free cortisol (UFC) excretion and response to cosyntropin stimulation were measured. There was no difference in UFC between any of the doses of HFA-BDP and CFC-BDP. Adrenal responsiveness to cosyntropin stimulation was normal in all but one patient. Two large 12 week phase III trials compared HFA-placebo, HFA-BDP 400 micrograms day-1 and CFC-BDP 800 micrograms day-1 (n = 347), and HFA-BDP 800 micrograms day-1 and CFC-BDP 1500 micrograms day-1 (n = 233). For HFA-BDP at either dose, CFC-BDP 800 micrograms day-1 and HFA-placebo, the number of patients with morning plasma cortisol concentrations below normal was less than 4.4% but was 14.6% for CFC-BDP 1500 micrograms day-1. The incidence of adverse events was lower in the HFA-BDP groups than in the CFC-BDP groups (P = 0.012). The data indicate that, at doses of up to 800 micrograms day-1, HFA-BDP is at least as well tolerated as CFC-BDP. Other studies have found that equivalent efficacy is reached at lower doses of HFA-BDP than CFC-BDP. Equivalent efficacy at a lower dose and equivalent safety at the same dose imply that HFA-BDP may have a more favourable risk: benefit ratio than CFC-BDP when used at the recommended lower doses.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chlorofluorocarbons; Cosyntropin; Cough; Cross-Over Studies; Drug Administration Schedule; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System

Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients; and both the DSCG and BDP groups had better clinical responses than the ketotifen group.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cromolyn Sodium; Female; Forced Expiratory Volume; Humans; Immunohistochemistry; Ketotifen; Male; Middle Aged; Mucous Membrane; Peak Expiratory Flow Rate

Inhaled glucocorticoids such as beclomethasone dipropionate, which are used in the treatment of asthma, may be associated with systemic adverse effects. To determine whether any systemic absorption following the inhalation of beclomethasone was a result of drug being absorbed from the lung (inhaled fraction) or the gastrointestinal tract (swallowed fraction), we studied normal subjects after the inhalation or swallowing of 2 mg beclomethasone dipropionate. Systemic activity was assessed using early morning cortisol suppression. Both inhaled and swallowed fractions produced significant systemic activity, the degree of which depended on the inhaler device used. Systemic activity was greater using a dry powder inhaler (52%) than using a metered dose inhaler with a large volume spacer (28%). These findings suggest that to limit potential adverse effects from high-dose beclomethasone dipropionate it is better to use a metered dose aerosol with large volume spacer than a dry powder.

Topics: Administration, Inhalation; Administration, Oral; Anti-Asthmatic Agents; Asthma; Beclomethasone; Glucocorticoids; Humans; Hydrocortisone; Nebulizers and Vaporizers

Thirty asthmatic patients were evaluated to assess the association of therapy with inhalatory corticosteroids and an educational program, EDUCASMA. Spirometric evaluation with Flow-Volume loop (MEDICAL GRAPHIC CPF-S), ambulatory FEP (mini WRIGHT meters) was performed. In regard of initial symptoms patients were qualified as moderate or severe. After two weeks of a screening period, they were randomized into 2 groups: a) beclomethasone; b) budesonide; respective doses in according to the initial status. During the study period (8 wks) they visited the medical Staff six or more times. In each visit the patients received clinical evaluation (i.e. clinical scoring), spirometry (i.e. FEV1), and FEP ambulatory revision. FEP x (mean), FEP delta, FEV1, and clinical scores values were matched at the start and at the end of the follow-up period. Non-parametric statistics were applied (Wilcoxon test) and significative changes were defined (p < 0.05).. 1) inhalatory corticosteroids therapy associated with a previous educational program could achieve early improvements of clinical scores; 2) in moderate asthma ambulatory FEP showed objective changes both in beclomethasone and budesonide treatments. It appears to indicate increasing changes very close to the clinical improvement; 3) the short period of our observation and the inflammatory condition of airways in severe asthma, could be explained as probable factors for the minor differences in the FEV1 evaluation; 4) no differences between budesonide and beclomethasone treatment were found.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Follow-Up Studies; Glucocorticoids; Health Education; Humans; Male; Middle Aged; Patient Education as Topic; Severity of Illness Index; Spirometry

Airway inflammation is a major factor in the pathogenesis of asthma. Inducing sputum by hypertonic saline is a noninvasive method of assessment of the airway inflammation in asthmatic patients. To investigate sputum induction as a method for assessing airway inflammation and to evaluate the effect of inhaled beclomethasone dipropionate (BDP) in asthmatic patients, we examined the bronchial hyperresponsibility (BHR), pulmonary function and differential cell counts in induced sputum of the patients before and after BDP therapy. In asthmatic patients, the percentage of eosinophils in induced sputum was significantly higher than that in non-asthmatic subjects. Ten patients with atopic asthma (four men and six women; mean [+/- SD] age, 30.5 +/- 12.4 years) participated. Their mean percentage of eosinophils (% eosinophils) in induced sputum fell from 22.9 +/- 7.2% to 13.9 +/- 8.3% (p < 0.05) by 3 months of BDP treatment. The percentage of eosinophils in induced sputum before BDP treatment was significantly correlated with the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1%) at baseline (r = -0.75, p < 0.05), but not with log Dmin at baseline (p = 0.18). The change in FEV1% between at baseline and post-treatment correlated significantly with the change in the sputum eosinophil percentage (r = -0.79, p < 0.01). In addition, there was a significant correlation between the change of log Dmin and the change of the sputum eosinophil percentage (r = -0.64, p < 0.05). In conclusion, analysis of induced sputum is a safe, noninvasive, repeatable and useful method to assess the clinical condition of bronchial inflammation in patients with bronchial asthma.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Eosinophils; Female; Humans; Lymphocyte Count; Male; Middle Aged; Regression Analysis; Sensitivity and Specificity; Sputum; Treatment Outcome

To better understand the effects of corticosteroid inhalation on asthma and asymptomatic bronchial hyperresponsiveness (BHR).. A double blind, randomized study was conducted to compare the effects of beclomethasone dry powder (BDP, 600 micrograms/day) inhalation with placebo on BHR and asthmatic symptoms in 59 students (12-18 yrs) for one year.. After one year of treatment, lgPD20-FEV1 increased significantly in asthmatics in the BDP group (0.385 +/- 0.424 vs 1.187 +/- 0.603 mumol histamine). Thirty percent of asthmatics in BDP group and 86% in the control group developed symptoms in this year (P = 0.076). There was no significant difference in lgPD20-FEV1 between the BDP and the control group in asymptomatic BHR students. However, none in the BDP group of asymptomatic BHR students developed asthmatic symptoms compared with 3 cases (15%) in control group. The accumulative symptom score showed significant difference between the BDP group and the control group in asymptomatic BHR students (1.50 +/- 2.54 vs 5.58 +/- 6.22, P < 0.01).. The results suggested that BDP could significantly relieve the severity of BHR and symptoms in asthmatics, and could have some prophylactic effects on the development of asthma in those with asymptomatic BHR.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male

In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Child; Circadian Rhythm; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Histamine H1 Antagonists; Humans; Ketotifen; Lung; Male; Methacholine Chloride; Peak Expiratory Flow Rate; Placebos; Pregnenediones

Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.

Topics: Administration, Inhalation; Adrenergic beta-Antagonists; Adult; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Isoxazoles; Male; Middle Aged; Respiratory Mechanics; Vital Capacity

Prevention of study patient attrition and assessment of its impact on outcome data are problems that receive little attention despite their obvious importance in asthma research.. The medical, demographic, and psychologic characteristics of asthmatic children and adults who dropped out of a yearlong medication trial were assessed to determine whether this group differed from those who completed the study, potentially introducing bias into the data set and interfering with completion of the study's objectives.. Profiles of 362 adult and pediatric asthmatic patient dropouts from the multicenter trial were contrasted with profiles of those who completed the study. Despite a 1-month prerandomization screening, 24% of patients failed to complete the trial for varied reasons, which largely included noncompliance and treatment dissatisfaction.. Although attrition rates were equal among adults and children, dropout-completer differentiation was not. Adult completers did not differ from dropouts in any variables. However, pediatric dropouts were more likely than completers to be female (67% and 36%, p = 0.008) and to have more reactive airways (PD20, 2.29 +/- 1.32 and 5.2 +/- 1.23, p = 0.05), to have reduced scores on tests of intelligence (Full Scale IQ, 102.2 +/- 2.6 and 112.5 +/- 1.6, p = 0.002) and problem solving (Wisconsin Card Sorting Test Error Scores, 39.8 +/- 4.1 and 29.1 +/- 2.0, p = 0.01), and to have increased behavioral problems (Child Behavior Checklist Total Problem Score, 60.7 +/- 2.5 and 53.6 +/- 1.1, p = 0.003).. These findings demonstrate the potential of patient attrition to bias outcome in clinical trials and underscore the necessity of: (1) preventing its occurrence, (2) correctly assessing its causes, and (3) determining its ultimate impact on study results. Strategies for each of these three tasks should be implemented at the study's initial planning stages.

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Behavior; Bias; Bronchodilator Agents; Child; Female; Humans; Intelligence Tests; Longitudinal Studies; Male; Middle Aged; Patient Dropouts; Problem Solving; Sex Factors; Theophylline; Treatment Refusal

To compare the efficacy of high-dose inhaled steroids in conjunction with IV steroids with that of IV steroids alone in the emergency treatment for acute asthma.. A double-blind, placebo-controlled, randomized trial was conducted on 60 ED patients presenting with acute asthma. All patients received nebulized salbutamol, and IV methylprednisolone, 80 mg at baseline and 40 mg at 6 hours. In addition to the above therapy, the experimental group received beclomethasone dipropionate (BDP) 7 mg over 8 hours via a metered-dose inhaler (MDI) attached to a holding chamber, while the control group received a placebo administered in the same fashion. Patients were treated on the protocol for 12 hours with the primary outcome measure being the change in % predicted FEV1.. Of 60 patients, 30 were randomized to BDP (age: 42 +/- 16 years; FEV1: 0.97 +/- 0.42 L) and 30 were randomized to placebo (age: 37 +/- 18 years; FEV1: 0.98 +/- 0.35 L). Spirometry and dyspnea measured by the Borg Scale improved significantly in both groups compared with baseline (p < 0.001). Changes in spirometry measures, dyspnea, and vital signs did not differ between treatment groups over the 12 hours of study (p > 0.05).. Inhaled BDP added to the standard regimen of IV methylprednisolone, and beta-agonist did not further improve flow rates or dyspnea scores measured for up to 12 hours after presentation to the ED.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methylprednisolone; Middle Aged; Prospective Studies; Respiratory Function Tests

Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings.

Topics: Adult; Airway Resistance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cold Temperature; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chromones; Double-Blind Method; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Procaterol; Substance Withdrawal Syndrome

In dermatological practice, allergy to topical corticosteroids used to treat eczema is a recognized and common event. The typical presentation is of an eczema which fails to improve or deteriorates with treatment. Topical corticosteroids are also used to treat mucosal disease. This study assesses allergy to inhaled corticosteroids in asthmatics. In the patient group selected, there was no evidence of relevant corticosteroid allergy.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Hypersensitivity; Female; Glucocorticoids; Humans; Immunoglobulin G; Intradermal Tests; Male; Methylprednisolone; Middle Aged; Pregnenediones

To investigate effects on adrenal function of fluticasone, a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate.. 34 children on high doses (400-909 micrograms/m2/d) of inhaled beclomethasone dipropionate or budesonide were recruited into a double blind, crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate, given using a standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline (after a two week run in), after six weeks treatment with an equal dose of beclomethasone, and after six weeks of treatment with half the dose of fluticasone, both given through a spacer device.. The comparison of effects between fluticasone and beclomethasone during treatment periods, although favouring fluticasone in all measured variables, reached significance only after correction for urinary creatinine excretion (tetrahydrocortisol and 5 alpha-tetrahydrocortisol geometric means: 424 v 341 micrograms/m2/d). The baseline data showed adrenal suppression in the children taking beclomethasone (total cortisol geometric means: 975 v 1542 micrograms/d) and a dose related suppression in the children taking budesonide. Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods.. Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses. The baseline data also support the claim that spacer devices should be used for the administration of high doses of inhaled topical steroids.

Topics: Administration, Topical; Adolescent; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma. They have been shown to reduce airway inflammation and hyperresponsiveness. The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma. In a double-blind study, two groups of 10 allergic asthmatics were randomly assigned to receive inhaled beclomethasone dipropionate (BDP), 500 micrograms b.i.d., or a matched placebo, two puffs b.i.d. The patients used inhaled salbutamol as needed. At the beginning of the study, and every month between February and June, the following parameters were assessed: lung function (forced expiratory volume in one second (FEV1); airway responsiveness (provocative dose of methacholine producing a 20% fall in forced expiratory volume in one second (PD20)), serum eosinophil cationic protein (ECP); and blood eosinophil count. All subjects recorded daily asthma symptoms, beta 2-agonist consumption and peak expiratory flow (PEF) values. In the placebo group, all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values (p < 0.001). BDP produced complete protection, although a slight change from baseline was found for symptom score (p < 0.01), beta 2-agonist consumption (p < 0.01), and eosinophil number (p < 0.05) in May, when the pollen load was highest. These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics. This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate, as documented by its effect on serum markers of airway inflammation.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Proteins; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Humans; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Pollen; Respiratory Function Tests; Ribonucleases; Seasons

To compare the efficacy and safety of a double-strength formulation of beclomethasone dipropionate (BDP 84) metered-dose inhaler (MDI) with that of beclomethasone dipropionate (BDP 42) MDI in the treatment of chronic asthma.. A 28-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter study.. Outpatient.. A total of 423 patients aged 12 to 65 years (mean range, 34 to 36 years) with moderate asthma (FEV1, 50 to 80% of predicted) who required long-term inhaled corticosteroids were enrolled.. Patients were randomized to receive BDP 84, two oral inhalations bid (336 microg/d), BDP 42, four oral inhalations bid (336 microg/d), or placebo. A fourth treatment arm administering BDP 84, eight oral inhalations bid (HD BDP 84; 1,344 microg/d) was also included to determine whether a dose-response relationship could be demonstrated.. Spirometry, clinical observations.. The three active treatments were significantly more effective (p < or = 0.01) than placebo at all time points in improving FEV1, the primary efficacy parameter; BDP 42 and BDP 84 were comparable to each other at every time point. Secondary pulmonary function tests (FVC, forced expiratory flow at 25 to 75% of FVC, and peak expiratory flow rate) showed similar results. All three active treatments were well tolerated. A dose response between 336 microg/d and 1,344 microg/d was demonstrated.. In this well-controlled 28-day study, BDP 42 and BDP 84 were shown to be comparable in efficacy and safety on a microgram-for-microgram basis.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Nebulizers and Vaporizers; Time Factors

There is evidence that downregulation and desensitization of airway beta 2-adrenoceptors (beta 2-AR) develops after continuous exposure to long-acting beta 2-agonists such as formoterol and salmeterol. To investigate the facilitatory effects of acute administration of systemic corticosteroid on bronchodilator subsensitivity, as might occur in the setting of acute asthma, 12 subjects with moderately severe asthma, with a mean FEV1 of 66% predicted, of whom were all receiving inhaled corticosteriod, were randomized to receive either inhaled placebo (PL) or inhaled formoterol (FM) 24 micrograms twice daily for 4 wk in a double-blind crossover study. Subjects were also genotyped in terms of beta 2-Ar polymorphism at loci 16 and 27. A dose-response curve (DRC) and duration-time profile for FM (12 to 108 micrograms) was produced 1 h after administration of placebo tablets and after injection at 3 wk, and 1 h after administration of oral prednisolone, 50 mg, and intravenous hydrocortisone, 200 mg, at 4 wk. Comparisons between treatments were made with area-under-curve (AUC) measurements as the change from baseline. There was a significant rightward shift in the DRC after FM as opposed to placebo for delta FEV1 (as AUC, L.h): 2.51 versus 4.22 (95% CI: 0.54 to 2.89; p = 0.01) and delta FEF25-75 (as AUC, L x 10(3)): 11.30 versus 19.94 (95% CI: 2.12 to 15.12; p = 0.01). This was significantly reversed by steroid (S) for FEV1 (FM versus FM+5): 2.51 versus 3.57 (95% CI: 0.11 to 2.27; p = 0.03) and for FEF25-75: 11.30 versus 18.47 (95% CI: 2.52 to 11.70; p = 0.005). Lymphocyte beta 2-AR density (log Bmax; fmol/10(6) cells) showed significant upregulation 3 h after steroid (FM+5 versus FM): 0.34 versus 0.24 (95% CI: 0.02 to 0.18; p = 0.01). For heart-rate response (as AUC, beats), there was subsensitivity with FM versus PL: 2,700 versus 5,200 (95% CI: 40 to 5,000; p < 0.001), and this was reversed by steroid (FM+5 versus FM): 9,600 versus 2,700 (95% CI: 4,900 to 8,800; p < 0.001). This reversal by systemic corticosteroid appears to be generally independent of beta 2-AR polymorphism at loci 16 and 27. In conclusion, we have demonstrated that bronchodilator subsensitivity occurs after regular inhaled FM in asthmatic patients, and is rapidly reversed by systemic corticosteroid. Thus, in acute asthma, systemic corticosteroid should be administered a soon as possible, in order to restore normal airway beta 2-AR sensitivity, particularly in patients who are receiving regular

Topics: Adrenergic beta-Agonists; Adult; Area Under Curve; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Tolerance; Ethanolamines; Female; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Pulmonary Ventilation

This study was undertaken to evaluate whether the therapeutic effect of pranlukast, a selective cysteinyl leukotriene (LT) C4/D4/E4 receptor antagonist, can be observed in patients with the non-atopic or atopic type of asthma, or in asthmatics taking oral steroids. Twenty-two patients with moderate to severe bronchial asthma receiving an inhaled corticosteroid (beclomethasone dipropionate) were treated with pranlukast (225 mg b.i.d.) for 4 weeks, and their peak expiratory flow (PEF) and asthmatic symptoms were monitored during the treatment period. In the patients with the non-atopic type of asthma (n = 13), an increase in their PEF was observed both in the morning and evening following a 4-week administration ofpranlukast, but the degree was slightly inferior to that in patients (n = 9) with the atopic type of asthma. On the other hand, no significant increase was observed in the patients (n = 6) taking oral prednisolone (PSL, 5-15 mg/day). Changes in the symptom score at the end of the 4-week treatment period were closely associated with those in the PEF values; namely, a significant improvement in symptom score was observed for patients with the atopic and non-atopic type of asthma, but no improvement for the patients taking oral PSL. Pranlukast, a selective LT receptor antagonist, will be a valuable asset in the treatment of bronchial asthma, especially asthma requiring no oral steroids.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Asthma; Beclomethasone; Chromones; Female; Glucocorticoids; Humans; Hypersensitivity, Immediate; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisolone

The aim of this study was to compare the effects of salmeterol and beclomethasone on lung function and symptoms in children with mild to moderate asthma. Sixty-seven children not treated with inhaled corticosteroids were randomized in a double-blind parallel study either to salmeterol 50 micrograms b.i.d. or beclomethasone 200 micrograms b.i.d. After one year, FEV1 significantly increased in the beclomethasone group, whereas in the salmeterol group there was a small reduction. Differences between groups were 14.2% predicted (p < 0.0001) and 7.0% predicted (p = 0.007) for pre- and postbronchodilator FEV1 values, respectively. PD20 methacholine decreased by 0.73 DD (p = 0.05) in the salmeterol group and increased by 2.02 DD (p < 0.0001) in the beclomethasone group. Morning and evening PEF and symptom scores improved in both groups, although more in the beclomethasone group. Asthma exacerbations, for which prednisolone was needed, were more frequent in the salmeterol group (17 versus two), as were the number of withdrawals due to exacerbations (six versus one). However, growth was significantly slower in the beclomethasone group (-0.28 SDS) compared with that in the salmeterol group (-0.03 SDS) (p = 0.001). We conclude that treatment with a moderate dose of beclomethasone is superior to salmeterol in children with mild to moderate asthma and recommend that salmeterol should not be used as monotherapy.

Topics: Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Body Height; Bronchial Provocation Tests; Bronchodilator Agents; Child; Double-Blind Method; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Severity of Illness Index; Vital Capacity

Twenty-nine of initially 42 infants with recurrent wheeze (20 male and 9 female) with an age range of 2.1-25.2 months were randomly assigned to receive either 100 micrograms beclomethasone dipropionate (BDP) combined with 200 micrograms salbutamol (group BDP-S, n = 9), 200 micrograms salbutamol (group S, n = 8), or placebo (group P, n = 6) 3 times daily for a 6 weeks' treatment period. Six infants had to be treated openly with BDP-S (group O, n = 6) because of deterioration in the disease state. Ten babies were excluded because of incomplete data and poor drug compliance and further 3 because of needed rescue medication. The drugs were inhaled from a metered dose inhaler through a baby-adapted spacer device, the Babyhaler. Control was assessed by symptom diaries, and infant whole-body plethysmography. Values of thoracic gas volume (TGV), airway conductance (Gaw) and specific airway conductance (sGaw) were calculated numerically independent of age and body length in percent predicted and in standard deviation scores using regression equations taken from healthy infants previously evaluated. Functional improvement was considered to have occurred when either TGV, and/or Gaw improved more than 2 SD from baseline. There was a significant improvement in the symptom score (p < 0.05), particularly concerning cough, in addition to a significant decrease in pulmonary hyperinflation (TGV: p < 0.05) and improvement of Gaw (p < 0.01) and sGaw (p < 0.01) in the BDP-S group when compared to the P group. No significant differences were found between the BDP-S and S group and/or between the S and P groups.. In wheezy infants BDP improves clinical status and lung function, when given in combination with salbutamol by a baby-adapted spacer device.

Topics: Administration, Inhalation; Albuterol; Analysis of Variance; Asthma; Beclomethasone; Bronchodilator Agents; Chi-Square Distribution; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Infant; Male; Respiratory Function Tests; Respiratory Sounds; Treatment Outcome

Previous studies demonstrated a downregulation of T-lymphocyte (CD3+ cells) activation in peripheral blood after treatment with inhaled corticosteroids in patients with asthma.. This study was carried out to evaluate the effect of inhaled corticosteroids on CD4 and CD8 T-lymphocyte activation, respectively.. We examined the expression of three surface activation markers (CD25, HLA-DR, and very late activation antigen 1) on circulating CD4+ and CD8+ T-cell subsets in subjects with asthma (n = 23) before and 8 weeks after treatment with inhaled beclomethasone dipropionate dry powder (daily dose, 800 microg).. Beclomethasone dipropionate treatment had a marked effect in reducing the expression of the activation marker CD25 (p < 0.01) in both CD4+ and CD8+ T-cell subsets in peripheral blood of patients with asthma. However, no correlation was found between the downregulation of CD4 and CD8 T-lymphocyte activation and the improvement in physiologic indices of disease activity.. These data add to the view that CD4+ and CD8+ T lymphocytes in peripheral blood of patients with asthma are in an activated state that is downregulated by inhaled corticosteroids.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Down-Regulation; HLA-DR Antigens; Humans; Integrin alpha1beta1; Integrins; Lymphocyte Activation; Receptors, Interleukin-2; T-Lymphocyte Subsets

As part of a development program to offer alternatives to chlorofluorocarbon (CFC) containing metered-dose inhalers, beclomethasone dipropionate has been formulated in a CFC-free system at three strengths: 50, 100, and 200 micrograms/actuation ex valve. To measure serum levels and dose proportionality of the beclomethasone derived from beclomethasone dipropionate, 13 mild to moderate asthmatic patients received a single dose of eight inhalations from each strength according to a double-blind crossover design. Seven patients were studied over 4 h and six patients over 12 h. For the total doses of 400, 800, and 1600 micrograms studied over 12 h, Cmax and AUC increased in a ratio of 1:1.8:3.1. A good correlation was seen between the fine-particle mass delivered and the in vivo performance of the three strengths. From a clinical point of view, the predictable increases in serum levels with an increase in dose will permit the clinician to effectively titrate a patient with this product.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Beclomethasone; Chlorofluorocarbons; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Half-Life; Humans; Male; Middle Aged; Nebulizers and Vaporizers

An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined.. We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed.. During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended.. Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Child; Double-Blind Method; Female; Glucocorticoids; Growth; Humans; Male; Placebos; Pulmonary Ventilation; Salmeterol Xinafoate

The efficacy of nedocromil sodium (NED) (8mg twice daily) in controlling the clinical symptoms of asthma (score symptoms), the pulmonary parameters (FEV1, FVC) and bronchial hyperreactivity to histamine was assessed. The study was performed in double-blind, cross-over and placebo-controlled way in 16 patients suffering from nonatopic, stable, moderate asthma treated with beclomethasone dipropionate (from 400 micrograms to 800 micrograms). NED and placebo were administered in a randomized way with 8-week wash-out period. Bronchial reactivity to histamine, was measured as the amount of histamine causing a 20% fall in FEV1 (PC20H in mg/ml). Treatment with NED did not change asthma symptom scores, FVC and FEV1. Decreased usage of beta 2-agonist was observed. NED did not influence bronchial hyperreactivity to histamine (xg PC20H was respectively 0.09 and 0.11 mg/ml after placebo and 0.06 and 0.08 after NED). The authors conclude that studies with NED in nonatopic asthmatics should be continued, but the dosage of the drug ought to be bigger and the time of treatment ought to be longer.

Topics: Adult; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Drug Administration Schedule; Drug Interactions; Female; Histamine; Humans; Male; Middle Aged; Nedocromil; Respiratory Function Tests; Treatment Outcome

The anti-asthmatic effects of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 microg x day(-1). The trial was designed as a randomized, double-blind, parallel-group study in several European countries. Sixty nine patients were treated for 6 weeks with theophylline plus BDP 400 microg x day(-1), compared to 64 patients treated with BDP 800 micro x day(-1). The mean+/-SD serum theophylline concentration was 10.1+/-4.2 mg x L(-1). Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p<0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p<0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 microg x day(-1) and beclomethasone dipropionate 800 microg x day(-1) in patients whose asthma is not controlled on beclomethasone dipropionate 400 microg x day(-1). The results support the use of theophylline as a steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prognosis; Respiratory Function Tests; Statistics, Nonparametric; Theophylline; Treatment Outcome

To evaluate the efficacy of combined Invigorating Kidney for Preventing Asthma (IKPA) tablets and beclomethasone dipropinate (BDP).. Fifty seven seasonal asthmatic patients were studied. They were randomly assigned to either of the two groups: the treated group (n = 32) treated with the IKPA tablets and inhalated BDP, the control group (n = 25) inhalated BDP singly. Measurements of serum eosinophil cationic protein (ECP), soluble IL-2 receptor (SIL-2), total eosinophil counts, spirometry and methacholine challenge were performed before and after treatment.. After 3 months' treatment and 6 months' observation the authors observed a significant improvement in both groups. The treated group had better clinical efficacy and the ECP level had reduced significantly, FEV1 increased greatly than the control group.. The two drugs influenced the function of eosinophils and and T lymphocytes and this might contribute to the efficacy.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Drug Therapy, Combination; Drugs, Chinese Herbal; Eosinophil Granule Proteins; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Male; Middle Aged; Receptors, Interleukin-2; Ribonucleases; Seasons; Tablets

Recent studies have demonstrated that RANTES, a member of the CC chemokine family affecting monocytes, T cells, basophils, and eosinophils, is expressed by several cell types. To investigate whether human bronchial epithelial cells can also express this chemokine, we investigated human bronchial epithelial cells for their ability to synthesize RANTES, both in vitro and in vivo. Additionally, we investigated the effect of treatment for 4 mo with inhaled corticosteroids on the expression of RANTES in these cells in vivo. Human bronchial epithelial cells cultured from surgical tissue expressed the mRNA for RANTES and synthesized RANTES, as demonstrated by polymerase chain reaction and immunocytochemical staining and enzyme-linked immunosorbent assay, respectively. Incubation of the cultures with 50 ng/ml of tumor necrosis factor-alpha (TNF-alpha) significantly increased the release of RANTES into culture medium after 18 to 48 h of incubation, an effect that was abolished by treatment of the cultures with anti-TNF-alpha antibody. RANTES was also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obtained from mild asthmatic patients before and after treatment with 500 micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched placebo for 4 mo. Quantitation, by color image analysis, of the percentage of epithelium staining for RANTES showed that treatment with BDP decreased the expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05). The numbers of EG2-staining cells in the epithelium were also reduced, from 790.1/mm2 to 203.3/mm2 (geometric mean; P < 0.01), after BDP treatment. These results suggest that human bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammation in allergic airways disease. Furthermore, corticosteroids may prevent airway inflammation by downregulating the expression of proinflammatory cytokines in the bronchial epithelium.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Asthma; Base Sequence; Beclomethasone; Bronchi; Cells, Cultured; Chemokine CCL5; Epithelium; Humans; Immunohistochemistry; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

The objective of this double-blind trial was to evaluate the corticosteroid-sparing effect of azelastine in patients with chronic bronchial asthma. A total of 193 subjects received either 6 mg of azelastine twice per day or placebo (in a 2:1 ratio) in combination with beclomethasone dipropionate (6 to 16 inhalations per day). The number of daily inhalations of the corticosteroid was reduced until maximum reduction or elimination was achieved. Patients then entered a 12-wk maintenance period, during which patients were maintained on their lowest possible dose of inhaled corticosteroid. Compared with placebo, the azelastine group had a statistically significantly greater overall median reduction in inhaled corticosteroids (4.9 puffs/day for azelastine versus 3.1 puffs/day for placebo; p < or = 0.010) during the maintenance period. The azelastine group also had a statistically significantly higher percentage of patients with reductions of > or = 50% and > or = 75% from the baseline level (53 and 31%, respectively, for azelastine versus 34 and 14%, respectively, for placebo; p < or = 0.028). The results demonstrated that azelastine, 6 mg twice per day, can reduce the need for inhaled corticosteroids in patients with chronic bronchial asthma and not lead to a deterioration in pulmonary function.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Data Interpretation, Statistical; Double-Blind Method; Female; Glucocorticoids; Histamine H1 Antagonists; Humans; Male; Middle Aged; Phthalazines; Placebos; Time Factors

To compare the efficacy of self management of asthma with traditional treatment.. 12 month prospective randomised trial.. Outpatient clinics in Finland.. 115 patients with mild to moderately severe asthma.. Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements.. Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life.. The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare.. Self management reduces incidents caused by asthma and improves quality of life.

Topics: Adult; Aged; Ambulatory Care; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Beclomethasone; Budesonide; Female; Finland; Glucocorticoids; Hospitalization; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Patient Education as Topic; Peak Expiratory Flow Rate; Pregnenediones; Prospective Studies; Quality of Life; Risk Factors; Self Care; Single-Blind Method; Treatment Outcome

Inhaled corticosteroids (ICS) in dosages above 1,000 micrograms/d may influence parameters of bone metabolism. Fluticasone propionate (FP) is a new ICS with a higher clinical potency than beclomethasone dipropionate (BDP) combined with negligible oral bioavailability. The aim of this study was to evaluate the effects of FP and BDP in clinically equipotent dosages on indices of bone metabolism and morning cortisol. FP 750 micrograms/d and BDP 1,500 micrograms/d were compared in a randomized, double-blind, crossover study consisting of two 6-wk treatment periods, each preceded by a 3-wk single-blind placebo period. Twenty-one nonsmoking asthmatic completed the study. FP had the same effect on FEV1 and peak expiratory flow as the double dose of BDP. Both treatments did not change morning cortisol. BDP decreased both osteocalcin and procollagen type 1 carboxyterminal propeptide, indices of bone formation, significantly by 18.5 and 21.9%, respectively. In contrast, FP did not change any variable of bone formation. FP and BDP did not increase type 1 collagen carboxyterminal telopeptide and deoxypyridinoline crosslinks, both markers of bone resorption. In changes in parameters of bone metabolism indicate adverse effects on bone quality in the long term, FP may offer an advantage over BDP.

Topics: Administration, Topical; Adolescent; Adult; Amino Acids; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Bone Resorption; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Osteogenesis; Peak Expiratory Flow Rate; Peptide Fragments; Procollagen; Single-Blind Method

Occupational asthma (OA) is a useful model for the study of asthma in humans. The possibility that inhaled corticosteroids, in addition to withdrawal from the workplace, could improve clinical and functional recovery from OA can be hypothesized. We assessed clinical, functional, and behavioral characteristics of 32 subjects (22 male, 10 female), in all but one of whom OA was confirmed by specific inhalation challenges induced by either high- (n=13) or low-molecular-weight (n=19) agents within 3 mo after cessation of exposure. In this randomized, crossover, double-blind study, subjects (paired for baseline PC20 and duration of symptoms after exposure) received either placebo or 1,000 micrograms of inhaled beclomethasone daily for 1 yr, followed by the alternate medication for 6 mo. Various clinical, functional, and behavioral parameters were examined at each 3-mo visit. Significant improvement in clinical (nocturnal symptoms, cough), functional (morning and evening peak expiratory flow rates), and behavioral (quality of life) parameters were detected in the active-treatment period, although the magnitude of the improvement was relatively small. Side effects (oropharyngeal, reduced cortisol) were similar in the placebo and treatment groups. Distinguishing subjects who started with the active preparation from those who were given placebo first showed that most clinical and behavioral parameters improved in the former instance, whereas there was no significant difference in the latter. We conclude that inhaled corticosteroids induce a small but significant overall improvement of the asthmatic condition in subjects with occupational asthma caused by high- and low-molecular-weight agents after withdrawal from exposure. The beneficial effect is, however, more pronounced if inhaled steroids are given early after diagnosis.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Candida albicans; Cough; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Molecular Weight; Occupational Diseases; Occupational Exposure; Oropharynx; Peak Expiratory Flow Rate; Quality of Life; Vital Capacity

A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled by BDP 500 microgram twice daily (or the equivalent). Following a run-in period, 738 patients at 72 centers were randomized to treatment for 24 wk in a double-blind, parallel-group study during which they maintained a daily record of peak expiratory flow rates (PEFRs) and symptom scores. At about 40 of the centers, bronchial hyperresponsiveness (BHR) to histamine was measured during and at 3 and 14 d after stopping treatment. Both groups taking salmeterol showed an improvement of more than 45 L/min in their morning PEFR and 30 L/min in their evening PEFR, compared with respective improvements of 16 L/min and 6 L/min in the group taking BDP 1,000. Both the SALM 50 and SALM 100 groups had a significantly increased percentage of symptom-free and rescue-free days and nights compared with the BDP 1,000 group, and there was no difference between the two salmeterol groups. None of the treatments altered BHR. Exacerbation rates did not differ among the three groups. We conclude that in this selected group of symptomatic patients taking BDP 500 micrograms twice daily, the addition of salmeterol provides better improvement in lung function and symptom control, without altering BHR or increasing exacerbation rates, than does doubling the dose of BDP.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Forced Expiratory Volume; Histamine; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

Twice-daily inhaled salmeterol produces rapid reduction in its acute bronchoprotective effect against methacholine in patients with mild asthma. This investigation examined this effect in patients with moderate asthma who were using inhaled corticosteroids.. Eight asthmatic volunteers who required inhaled corticosteroids for control of their symptoms and who were able to withhold treatment with beta 2-agonists for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 microg twice a day for seven doses, and placebo in similar fashion, with a 7-day or greater washout between these periods. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler, 10 min post-200 microg salbutamol.. Baseline FEV1 measurements before doses 3, 5, and 7 of salmeterol, ie, 12 h after salmeterol, were significantly higher than all other baseline values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) following the third dose of salmeterol (6.8 mg/mL) was significantly lower than after the first dose of salmeterol (12.0 mg/mL; p=0.031), and this reduction of bronchoprotection persisted following doses 5 and 7. The methacholine PC20 10 min postsalbutamol measured after the salmeterol period was significantly lower than after placebo (5.6 vs 13.3 mg/mL; p<0.001).. Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and persisted after the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was also significant after regular use of salmeterol for seven doses. These effects, in subjects using inhaled corticosteroids regularly, were similar to the those previously seen in patients with mild asthma using as-required beta 2-agonists only, indicating that tolerance is not prevented by use of inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Placebos; Pregnenediones; Salmeterol Xinafoate; Tachyphylaxis

To determine if a comprehensive long-term management program, emphasizing inhaled corticosteroids and patient education, would improve outcomes in adult African-American asthmatics a nonrandomized control trial with a 2-year intervention was performed in a university-based clinic. Inclusion criteria consisted of (> or = 5) emergency department (ED) visits or hospitalizations (> or = 2) during the previous 2 years. Intervention patients were volunteers; a comparable control group was identified via chart review at hospitals within the same area and time period as the intervention patients. Individualized doses of beclomethasone with a spacer, inhaled albuterol "as needed," and crisis prednisone were the primary therapies. Environmental control, peak flow monitoring, and a partnership with the patient were emphasized. Detailed patient education was an integral part of management. Control patients received usual care from local physicians. ED visits and hospitalizations for 2 years before and 2 years during the intervention period were compared. Quality of life (QOL) measurements were made at baseline and every 6 months in the intervention group. Study group (n = 21) had a significant reduction in ED visits (2.3 +/- 0.2 pre-intervention versus 0.6 +/- 0.2 post-intervention; P = 0.0001). Control group (n = 18) did not have a significant change in ED visits during the 2-year post-intervention period (2.6 +/- 0.2 pre-intervention versus 2.0 +/- 0.2 post-intervention; P = 0.11). Both groups had significant reductions in hospitalizations, but the study group had a greater reduction. Sixty-two percent of study patients had complete elimination of ED visits and hospitalizations, whereas no control patients had total elimination of the need for institutional acute care. QOL in the study patients revealed significant improvements for most parameters. A comprehensive long-term management program emphasizing inhaled corticosteroids combined with other state-of-the-art management, including intensive patient education, improves outcomes in adult African-American asthmatics.

Topics: Adrenal Cortex Hormones; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Black or African American; Drug Therapy, Combination; Emergencies; Hospitalization; Humans; Patient Education as Topic; Prednisone; Program Evaluation; Quality of Life; Treatment Outcome

The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. PHASE 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta 2-agonist plus inhaled corticosteroid (BA + CS) was more effective in improving the FEV1 and the provocative concentration of histamine causing a 20% reduction in FEV1 (PC20) than treatment with a beta 2-agonist plus anticholinergic (BA + AC) or placebo (BA + PL). PHASE 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 micrograms beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA +/- AC) could also improve FEV1 and PC20 to the same degree. A distinction was made between patients with predominantly asthma (high baseline reversibility, delta FEV1 > or = 9% of predicted), and predominantly COPD (low baseline reversibility, delta FEV1 < 9% of predicted).. Improvement of FEV1 percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p = 0.31) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively). PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p = 0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p = 0.19).. Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV1, improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Asthma; Beclomethasone; Bronchial Provocation Tests; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Residual Volume; Terbutaline; Time Factors; Total Lung Capacity

Our purpose was to study the effect of inhaled corticosteroids on asthma exacerbations in pregnancy.. We prospectively studied 84 pregnant women with 105 asthma exacerbations. Women were hospitalized if the forced expiratory volume in 1 second was < 70% after sequential bronchodilator therapy. They were randomly assigned to receive either intravenous aminophylline and inhaled beta 2-adrenergic receptor agonist or intravenous methylprednisolone and a beta 2-adrenergic receptor agonist. At discharge women were randomly assigned to receive either inhaled beclomethasone, beta 2-adrenergic receptor agonist, and an oral corticosteroid taper or a beta 2-adrenergic receptor agonist and a corticosteroid taper.. Sixty-five (62%) of 105 women with exacerbation required hospitalization. Aminophylline did not shorten response time or decrease hospital stay. Readmission rate was decreased by 55% in women given inhaled beclomethasone (33% vs 12%, p < 0.05, odds ratio 3.63, 95% confidence interval 1.01 to 13.08). Pregnancy-induced hypertension and cesarean delivery were increased over those of the general population.. Intravenous aminophylline offers no therapeutic advantages. Continuous inhaled corticosteroids reduced the need for subsequent admissions.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Aminophylline; Asthma; Beclomethasone; Bronchodilator Agents; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Methylprednisolone; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Prospective Studies; Treatment Outcome

The effects of inhaled beclomethasone dipropionate (BDP) on asthma symptoms and infiltration of the bronchial mucosa by inflammatory cells were investigated in an open study of 10 patients with mild-to-moderate nonatopic bronchial asthma. Asthma scores were recorded in an asthma diary. Peak expiratory flow (PEF), PEF diurnal variation (PEF%), forced expiratory volume in one second (FEV1%), methacholine airway hypersensitivity (minimum dose of methacholine) (Dmin) were measured. Biopsy of the bronchial mucosa was performed before and after 8 weeks of treatment with BDP (400 micrograms.day-1). The following inflammatory cells were immunostained: eosinophils with anti-EG2; mast cells with AA1; neutrophils with NP57; T-lymphocytes with anti-CD3, CD4, and CD8; and activated T-lymphocytes with anti-CD25. There was a significant improvement in the asthma symptom score, PEF%, FEV1%, and Dmin after BDP therapy and the number of EG2-, AA1-, CD3-, CD4-, and CD25-positive cells decreased significantly. We conclude that inhaled beclomethasone dipropionate inhibited inflammatory cell infiltration of airway tissue and that associated with this there was an improvement of symptoms in this open study of inhaled beclomethasone dipropionate in a group of nonatopic asthmatic subjects.

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biopsy; Bronchi; Bronchial Provocation Tests; Cell Count; Eosinophils; Female; Humans; Lymphocyte Count; Male; Mast Cells; Middle Aged; Mucous Membrane; Nebulizers and Vaporizers; Neutrophils; T-Lymphocyte Subsets

Salmeterol is a selective long-acting beta 2-agonist bronchodilator considered to have added anti-inflammatory effects, but this is controversial. We investigated the effects of a single dose of salmeterol, 100 micrograms, on the physiological and inflammatory responses to inhaled allergen and compared these with the effects of a single dose of beclomethasone, 500 micrograms, and of placebo. Eight atopic adults with mild stable asthma, treated only with inhaled short-acting beta 2-agonist when needed, attended the laboratory sequentially for screening tests, two single-blind control inhalation tests preceded 30 min by placebo or salmeterol and three allergen inhalation tests preceded by placebo, salmeterol or beclomethasone double-blind in random order. Airway responsiveness to methacholine (assessed as the provocative concentration of methacholine producing 20% fall in forced expiratory volume in one second (PC20)), induced sputum eosinophils, blood eosinophils and serum eosinophil cationic protein (ECP) were examined before and 7-48 h after treatment. The statistical power to detect twofold changes in blood and sputum parameters was > or = 90%. Salmeterol inhaled before allergen challenge completely prevented the early asthmatic response, late asthmatic response and fall in methacholine PC20 at 24 h, and produced additional bronchodilatation. These effects were similar to those obtained by the inhalation of a single dose of salmeterol before the control inhalation test, and significantly better than those observed after a single dose of beclomethasone inhaled before the allergen test. Beclomethasone had no effect on the early asthmatic response or on the fall in methacholine PC20 at 24 h but partially inhibited the late asthmatic response. Neither salmeterol nor beclomethasone had any significant effect on sputum or blood inflammatory changes 7-48 h after allergen inhalation. In conclusion, whilst salmeterol had no demonstrable anti-inflammatory action in sputum after allergen challenge in asthma, neither did a single dose of the positive anti-inflammatory control, beclomethasone. The latter result excludes a more positive judgement on the possible anti-inflammatory action of salmeterol. However, the results do indicate that potent functional effects of a single dose of salmeterol can mask the airway inflammatory cell influx caused by inhaled allergen.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Albuterol; Allergens; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Salmeterol Xinafoate; Spirometry; Sputum; Treatment Outcome

We studied the usefulness of 18 weeks of therapy with two high doses of inhaled beclomethasone dipropionate (BDP) in the management of severe asthma in adults. The patients had asthma symptoms that had not been controlled by combination therapy with BDP (800 micrograms/day) and bronchodilators. They were divided into two groups. Patients in group A (n = 16) were treated with 1800 micrograms/day of BDP and bronchodilators. Patients in group B (n = 10) were treated with 1400 micrograms/day of BDP and bronchodilators. BDP was inhaled via a large spacer (Volumatic). Eleven patients in group A and 6 patients in group B had been given an oral steroid regularly before the study. Asthma symptom scores, peak expiratory flow (PEF), pulmonary function, bronchial reactivity to methacholine, the total amount of oral steroid, and adrenocortical function were recorded. Results. 1) Clinical characteristics before the start of the study did not differ between groups. 2) Asthma symptom scores decreased to a greater extent in patients who received the higher dose of BDP than in those who received the lower dose. 3) Only the higher dose of BDP significantly increased evening and morning % PEF, as measured 6 weeks and 8 weeks after the start of the treatment. 4) Only the higher dose of BDP significantly increased the FEV1 and the PC20 for methacholine. FVC did not increase. 5) Only the higher dose of BDP significantly decreased the total amount of oral steroid needed to control asthma. 6) Results of the rapid ACTH test indicated that neither dose of BDP suppressed adrenocoritical function. Furthermore, the serum cortisol level measured early in the morning increased to within the normal range in the three patients in whom oral steroid therapy could be reduced or stopped after treatment. These data indicate that 1800 micrograms of BDP per day is more effective than 1400 micrograms/day at the beginning of long-term management of severe chronic asthma in adults whose symptoms are not controlled with the combination of 800 micrograms/day BDP and bronchodilators. Therapy with a higher dose (at least 1600 micrograms/day) of an inhaled steroid is more useful and should be promptly begun to treat severe asthma.

Topics: Administration, Inhalation; Adult; Age of Onset; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Cetirizine; Cromolyn Sodium; Glucocorticoids; Histamine H1 Antagonists; Humans; Nasal Decongestants; Recurrence; Rhinitis, Allergic, Perennial; Terfenadine

1. Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows. This study was designed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function. 2. Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone were studied during four different drug treatments over 3 months. Subjective self-assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow, using a coded electronic peak flow meter. This was recorded not less than three times daily on diary cards. Observations were recorded during the second week of each of four treatments: (i) a run-in period using only inhaled salbutamol as required, (ii) inhaled beclomethasone, (iii) inhaled cromoglycate and (iv) oral theophylline at a dose adjusted to achieve blood levels of 10-20 mg/l. Inhaled salbutamol was permitted during the other treatments as required. Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment. Dynamic lung volumes were measured in the clinic before the study and after each treatment period. 3. In the group as a whole, theophylline improved lung function (mean peak flow and dynamic lung volumes) without affecting mean visual analogue scores, beclomethasone improved mean visual analogue scores with much less effect on lung function, while cromoglycate had a small though consistent effect on both. 4. Perception of asthma, measured by the relationship between peak flow rate and visual analogue scores, was unaffected by cromoglycate. On theophylline, perception of asthma was heightened in five subjects despite a definite improvement in their peak flow. On beclomethasone, perception of asthma was reduced in most subjects, often with no discernible improvement in mean peak flow or dynamic spirometry. 5. Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition. Theophylline may produce a paradoxical increase in awareness of asthma in some individuals. With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow.

Topics: Adult; Albuterol; Asthma; Beclomethasone; Bronchoconstriction; Bronchodilator Agents; Cromolyn Sodium; Female; Humans; Lung; Lung Volume Measurements; Male; Middle Aged; Peak Expiratory Flow Rate; Perception; Theophylline

A "survival" model offers certain ethical and practical advantages over alternative experimental designs if used to compare antiasthmatic inhaled steroid formulations. The model requires an objective daily measure of therapeutic effect (e.g., peak expiratory flow rate, which may be expressed as the lower of two daily measurements (LPF) or as diurnal variability (DVPF). The relative efficiency of these two measures is unknown.. This study was conducted to determine the relative efficiency of LPF and DVPF.. We analyzed data from a placebo-controlled comparison of an active inhaled formulation of budesonide versus an inactive oral formulation. The primary outcome measure in this design is the number of days from the time the test treatments start until a statistically significant deterioration occurs from an optimal asthma control value established at baseline.. DVPF proved less sensitive than LPF; that is, fewer patients relapsed during the 8-week trial period: 32 versus 41, respectively. Also, the median interval until relapse was longer: 24 versus 9 days. With LPF, inhaled budesonide proved more effective than placebo or oral budesonide (p = 0.03), whereas DVPF failed to discriminate among the test treatments (p = 0.38). LPF correlated with all three symptom indices (p > or = 0.003) and two of three spirometric indices measured concomitantly (p < or = 0.04). DVPF did not correlate with any index (p > or = 0.10).. In this experimental model, LPF proved more sensitive and valid than DVPF as an indicator of differences in antiasthmatic potency between two inhaled steroid formulations.

Topics: Administration, Inhalation; Administration, Oral; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Circadian Rhythm; Double-Blind Method; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones; Retrospective Studies

The aim of this study was to investigate the efficacy and adverse effects of methotrexate (MTX) in the treatment of severe chronic asthma in 12 patients with severe asthma requiring continuous treatment with oral steroids at the Outpatient Department of Helsinki University Central Hospital. The study was a randomised, double-blind placebo-controlled trial of methotrexate treatment 15 mg weekly on a crossover basis over 24 weeks. During the 2 weeks baseline phase the mean dose of oral steroids administered was 10.9 (3.2-28) mg.day-1, and the mean dose of inhaled steroids administered was 2.3 (1.6-3.2) mg budesonide or beclomethasone. The average dose of oral steroids administered was 12.8 mg.day-1 during the last 2 placebo weeks but only 7.9 mg.day-1 during the last 2 weeks with MTX treatment. The reduction in daily dose of oral steroids was 38%, while daily bronchodilator use was reduced by 22%. During MTX treatment the patients experienced significantly less wheezing, dyspnoea and coughing. Nine out of 12 patients reported better asthma control during MTX treatment. The peak expiratory flow rate (PEF) 1-s forced expiratory volume (FEV1) values did not differ between MTX and placebo treatments. There was no statistical correlation between serum MTX concentration and clinical improvement. No serious adverse effects of MTX were found during the study. It was concluded that low-dose MTX may be beneficial for severe chronic asthma and that this therapy is well tolerated by patients.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aerosols; Analysis of Variance; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Folic Acid Antagonists; Forced Expiratory Volume; Humans; Male; Methotrexate; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Inhalation; Adult; Annexin A1; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Eicosanoids; Female; Glucocorticoids; Histamine; Humans; Male; Middle Aged; Pulmonary Alveoli; Respiratory Function Tests; Smoking

This study was carried out to determine whether serum eosinophil cationic protein (ECP) represents a sensitive marker for disease activity in atopic asthmatic patients during the pollen season. The study, in double-blind fashion, was performed between February and June 1994. Two groups of 10 seasonal asthmatic patients randomly received two different treatments. The first group was treated with inhaled beclomethasone dipropionate (BDP) 500 micrograms bid; the second received a matched placebo (P). At the beginning and every month, blood samples for determination of ECP and eosinophil count were collected and lung function (FEV1) and methacholine responsiveness (PD20) were performed. Subjects recorded daily symptoms of asthma, salbutamol consumption, and peak expiratory flow (PEF) values. In the P group, all indices, except FEV1, showed significant changes during the pollen season (P < 0.001). In the BDP group, significant changes were detected for symptom score (P < 0.01), salbutamol consumption (P < 0.01), and eosinophil number (P < 0.05). Between the two groups, significant differences for symptom score (P < 0.001), salbutamol consumption (P < 0.001), ECP levels (P < 0.05), eosinophil count (P < 0.02), PD20 methacholine (P < 0.02), and PEF values (P < 0.01) were detected. Changes in serum ECP significantly correlated with changes in other parameters (P < 0.001), except FEV1. Our results provide evidence that serum ECP is a sensitive marker for monitoring of the disease activity in seasonal asthma. Furthermore, it may offer a useful tool for estimating treatment efficacy.

Topics: Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Bronchial Provocation Tests; Bronchodilator Agents; Double-Blind Method; Eosinophil Granule Proteins; Eosinophils; Female; Forced Expiratory Volume; Humans; Leukocyte Count; Male; Methacholine Chloride; Middle Aged; Peak Expiratory Flow Rate; Pollen; Ribonucleases; Seasons; Skin Tests

Cetirizine is a non-sedating H1 antihistamine which is effective in the treatment of allergic rhinitis and urticaria. It inhibits eosinophil and basophil chemotaxis in late cutaneous allergic reactions in skin windows. Its effect on early (EAR) and late asthmatic reactions (LAR) is less certain.. We examined the effect on EAR and LAR of 3 days treatment with oral cetirizine (15 mg twice daily) compared with a single dose of inhaled beclomethasone 10 min prior to allergen challenge in a placebo-controlled (oral and inhaled) double-blind cross-over design with three treatment arms separated by 14 days.. Cetirizine did not significantly inhibit either the EAR or LAR documented by maximum percentage fall in FEV1 (0-3 and 6-9 h) or as area under the curve (AUC between 0 and 3 and 6-9 h). Beclomethasone inhibited the LAR compared with placebo (P = 0.02) when expressed as AUC (6-9 h). This did not quite reach statistical significance (P = 0.06) when expressed as maximal percentage late fall in FEV1 between 6 and 9 h. A greater than twofold increase in airways responsiveness to methacholine was observed 3 h after challenge which was significantly reduced by beclomethasone compared with placebo (P < 0.02) and cetirizine (P < 0.05). The data suggest that oral cetirizine does not significantly inhibit either the EAR or LAR. Beclomethasone inhibited both the early increase in airways responsiveness and the subsequent LAR. Our study also confirms the view that early increases in airway responsiveness precede the late response and suggests that these associated events are not dissociable by the pharmacological treatments employed in this study.

Topics: Administration, Inhalation; Administration, Oral; Adult; Allergens; Antigens, Dermatophagoides; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Glycoproteins; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Poaceae; Time Factors

The aim of this study was to assess the efficacy and safety of inhaled salmeterol 100 micrograms b.d. (SM) versus inhaled salbutamol 400 micrograms q.d.s. (SB), both via the Diskhaler, when added to concurrent treatment, in asthmatic patients who were not controlled on high doses of inhaled steroids (> or = 1,500 micrograms beclomethasone dipropionate (BDP) or equivalent daily). This was a multicentre, parallel group, double-blind study in which 190 patients with a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) of 30-75% predicted and 15% reversibility to inhaled bronchodilator were randomized to treatment for 6 weeks. In the SM group, morning PEFR increased from 281 to 315 L-min-1 during treatment and in the SB group from 311 to 315 L.min-1 (p < 0.001). The SM group showed significantly better reduction in diurnal variation, from 39 to 22 L.min-1 during treatment, than the SB group (34 to 37 L.min-1) (p < 0.001). There was a significantly greater improvement in FEV1 in the SM group (from 1.63 to 1.85 L) than in the SB group (from 1.79 to 1.84 L). The SM group had significantly more symptom-free nights than the SB group (p < 0.001), and also more "rescue-free" nights (p = 0.04). The adverse event profile was similar in both groups. This study indicates that in asthmatic patients, not controlled on high-dose inhaled steroids, inhaled salmeterol 100 micrograms b.d. significantly improves lung function and reduces asthma symptoms.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Circadian Rhythm; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos; Pregnenediones; Salmeterol Xinafoate

This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers

While the side effects of oral glucocorticoids are well recognised there is debate about the systemic effects of high doses of inhaled glucocorticoids such as beclomethasone dipropionate and how these compare with the effects of oral prednisone.. To compare the effects of different doses of oral prednisone and inhaled beclomethasone dipropionate (BDP) on changes in circulating leukocytes.. Changes in different subsets of circulating leukocytes were measured as an index of the systemic effects of inhaled BDP and oral prednisone. We compared the effects of inhaled placebo and 500 and 1000 micrograms of inhaled BDP with oral placebo and 2.5, 5 and 10 mg of prednisone in eight healthy volunteers. Leukocyte numbers were measured before and four hours after each dose of medicine.. Compared with inhaled placebo, 1000 micrograms of inhaled BDP led to a significant increase in neutrophils as a percentage of the total white count (p < 0.05) and a significant decrease in the total lymphocyte number (p < 0.05) and in the number of CD4 lymphocytes (p < 0.05). For 1000 micrograms BDP the increase in the % neutrophil count was 8.55% (95% CI 5.17 to 11.93) and the fall in lymphocyte numbers was -0.14 x 10(9)/L (95% CI 0.06 to -0.34) while 2.5 mg prednisone led to an increase in the % neutrophil count of 9.31% (95% CI 5.82 to 12.80) and a fall in lymphocyte numbers of -0.07 x 10(9)/L (95% CI 0.05 to -0.19).. The systemic effects of 1000 micrograms inhaled BDP and 2.5 mg of prednisone are similar.

Topics: Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Confidence Intervals; Double-Blind Method; Humans; Leukocyte Count; Leukocytes; Multivariate Analysis; Prednisone

Sixty-eight asthma patients of Cold type were randomly divided into two groups, 34 for each group. The treated group was treated with Chinese herbal medicine Wenyang Tongluo Mixture (WYTLM), the control group was treated with Salbutamol orally and beclomethasone dipropionate aerosol. After 8 weeks of treatment, the results showed that there was no significant difference between the short-term total effective rate of the two groups (P > 0.05). Results of followup 1 year after withdrawal of treatment, showed that 9 patients (26.47%) in the treated group and 2 (5.88%) in the control group were cured clinically, it indicated that the long-term curative rate of the former group was higher than that of the latter group significantly (P < 0.05). And the effect of treated group on eliminating Asthenia-Cold symptoms, improving pulmonary ventilation function, regulating adrenergic beta-receptors of peripheral blood lymphocyte and decreasing the serum level of 5-hydroxytryptamine was more superior to that of control group (P < 0.05-0.01). This study provided some objective basis for using WYTLM in preventing and treating asthma of Cold type.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drugs, Chinese Herbal; Follow-Up Studies; Humans; Male; Middle Aged; Receptors, Adrenergic, beta; Respiratory Function Tests

Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test.. Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study.. Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate.. These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate

Quality of life (QOL) is commonly measured in asthma clinical trials by a questionnaire given before and after treatment. A structured asthma QOL daily diary provides more restricted information but on a daily basis. The validity and use of such a QOL diary was examined in a clinical trial in which two asthma treatments were compared.. The effects of low dose inhaled steroid (400 micrograms beclomethasone dipropionate, BDP) combined with the long acting beta 2 agonist salmeterol (100 micrograms) (n = 220) was compared with high dose inhaled steroid (1000 micrograms BDP) (n = 206) in asthmatic outpatients in a double blind, parallel group study. Outcome measures consisted of a combined diary for peak expiratory flow (PEF) rate, symptoms, and problems, and an asthma-specific QOL questionnaire, the Living with Asthma Questionnaire.. The QOL diary correlated with the QOL questionnaire for both cross sectional and longitudinal assessments. Cross sectional correlations with PEF were higher for the QOL questionnaire than the QOL diary, but longitudinal correlations with PEF were higher for the diary than the questionnaire. Treatment with low dose steroid/salmeterol compared with high dose steroid produced better lung function, better QOL as measured by diary, and reduced night time wakenings, but treatment differences were not obtained with the QOL questionnaire nor for daytime symptoms. Diary assessed QOL was a better predictor of low PEF than diary assessed symptoms. Compliance with diary completion was good but there were floor or ceiling effects in the QOL diary records of about 25% of patients.. Structured QOL diaries are valid instruments that appear to be more responsive to longitudinal change in clinical trials than a QOL questionnaire, but QOL questionnaires provide a more sensitive cross sectional measure of disease severity. Floor and ceiling effects are found in some patients' QOL diaries which limit their usefulness. QOL diary problem events occur during the troughs of a peak flow graph, while symptoms are more widely distributed with respect to peak flow.

Topics: Adolescent; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Sectional Studies; Double-Blind Method; Drug Combinations; Female; Humans; Longitudinal Studies; Male; Medical Records; Middle Aged; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate; Surveys and Questionnaires; Treatment Outcome

A randomized study was conducted for 4 weeks to evaluate the effect of twice daily inhalation of beclomethasone dipropionate (BDP) inhalation (group A) as compared to four times a day inhalation (group B) in chronic asthma. Patients were randomly allocated to receive BDP at a dosage of eight puffs twice daily (800 micrograms/day, group A) or four puffs four times daily (800 micrograms/day, group B). Forty four patients entered the study but eleven were excluded because of their insufficient records or unfitness to eligibility criteria. There was no significant difference in patients' characteristics such as types, and severity of diseases between the two groups. Daily keeping of symptom scores, twice daily measurement of morning and night peak expiratory flow (PEF) and checking of the drug consumption were performed throughout the study. There was no significant difference in the mean %PEF either at 2 and 4 weeks at the study between the two groups. Symptom scores, asthmatic scores, bronchial hyperresponsiveness, pulmonary function tests (FVC, FEV1, FEV1%) and serum cortisol levels also showed no significant difference between the two groups. These results indicate that twice daily inhalation of BDP (800 micrograms/day) for four weeks caused the same effects on the patients with chronic bronchial asthma as 4 times daily inhalation did. Therefore, twice daily inhalation therapy with BDP is recommended for chronic bronchial asthma patients.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chi-Square Distribution; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Glucocorticoids; Humans; Middle Aged; Placebos; Prednisolone; Pregnenediones; Respiratory Function Tests; Respiratory Therapy; Time Factors

To determine whether inhaled corticosteroids can be discontinued in the stable phase of asthma or chronic obstructive pulmonary disease (COPD) or if this therapy should be continued.. Nonrandomized open uncontrolled 5-year trial.. Prospective study in general practice.. Forty-eight patients with steroid-dependent asthma or COPD who had shown a decline in forced expiratory volume in 1 second (FEV1) of at least 80 mL per year and at least one exacerbation per year during the first 2 years of bronchodilator treatment. Subjects were treated additionally with inhaled steroids for another 2 years and were finally given the option to stop using steroids. Sixteen patients were willing to stop using beclomethasone and were studied for another year. No recruitment bias took place in this consecutive sample in the fifth year of follow-up. Two of 16 patients developed carcinomas and dropped out.. Two years of bronchodilator treatment alone (400 micrograms of salbutamol or 40 micrograms of ipratropium bromide four times daily), followed by 2 years of additional inhaled corticosteroid treatment (400 micrograms of beclomethasone two times daily), and finally 1 year of bronchodilator treatment alone.. Decline in lung function (FEV1), change in bronchial hyperresponsiveness, indicated by a provocative concentration of histamine causing a 20% fall in FEV1 (PC20), morning peak expiratory flow rate (PEFR), diurnal PEFR, week-to-week variation of PEFR, bronchial symptoms, and exacerbations.. The course of FEV1 during the year in which beclomethasone was discontinued was not significantly different when compared with the 2-year period of beclomethasone treatment. Neither did the course of PC20, morning PEFR, diurnal PEFR, symptom score, and exacerbation rate change. Only the week-to-week variation of the PEFR increased after discontinuing steroids.. Discontinuing inhaled steroids is possible in some patients with asthma or COPD after 2 years of regular treatment. This might indicate that for certain groups of patients with mild asthma or COPD, periodic treatment schedules with inhaled steroids is the treatment policy for the future.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Time Factors

To study the effects of an inhaled steroid on airway hyperresponsiveness (AHR) in chronic stable asthma, AHR was measured every month for 1 year in seven patients after their asthma had stabilized, i.e., when they had no wheezing or dyspnea, and their peak expiratory flow rates (PEFR) were at least 80 percent of the highest value. During the study period, no patient wheezed or had dyspnea, and daily variation in PEFR was less than 20 percent. In six patients, FEV1 was stable, and PEFR was always at least 80 percent of the highest value. AHR became less severe, by a factor of at least 2, in five of these six patients, but one patient's condition did not improve. The one patient whose PEFR fell below 80 percent of the highest value had more than a 4-fold increase in the severity of AHR. In conclusion, the severity of AHR can be reduced, even in patients with chronic stable asthma, if daily PEFR can be maintained in an optimal range by long-term use of inhaled corticosteroids.

Topics: Administration, Inhalation; Aged; Asthma; Beclomethasone; Bronchial Hyperreactivity; Chronic Disease; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Female; Humans; Male; Middle Aged; Prednisolone

Chlorofluorocarbon-propelled metered dose inhalers are facing a worldwide ban. Dry powder inhalers have been developed for the agents used in treatment of asthma.. Our objective was to compare the effects of two inhaled glucocorticosteroids in dry power inhalers: budesonide (delivered via Turbuhaler) and beclomethasone dipropionate (delivered via Rotahaler).. A randomized, crossover study with two steroid-treatment periods of 8 weeks. At the end of the study, the treatment with the inhaled steroid was stopped for 4 weeks. Sixteen adult patients with moderately severe asthma participated. Before the study all patients were treated with an inhaled steroid in a median dose of 0.60 mg/day (range 0.15-0.80); during the study they received 0.20 mg twice daily. Peak expiratory flow rate was measured twice daily at home throughout the study, lung function was assessed every fourth week and airway responsiveness was measured before and after each period. Preference concerning efficacy and inhaler type was assessed at the end of the study.. Twelve patients completed the study. Lung function, airway responsiveness, and symptoms deteriorated significantly in the steroid-free washout period; this period had to be shortened in 5/12 patients. Mean morning peak expiratory flow was significantly higher during budesonide treatment than during beclomethasone dipropionate treatment, the difference being 17 L/min (95% C.I.: 2-32 L/min, P = .026). Airway responsiveness improved 1.1 doubling concentrations after budesonide treatment, but decreased 0.3 doubling concentrations after beclomethasone dipropionate treatment. The difference between the values after budesonide and beclomethasone dipropionate treatment was 1.4 doubling concentrations (95% C.I.: 0.4-2.4 doubling concentrations, P = .033). Forced expiratory flow in one second improved slightly more during budesonide than during beclomethasone treatment. The difference was 4.3% predicted (95% C.I.: -0.7-9.3%). Most patients reported budesonide Turbuhaler to be more effective (10 versus 0) and easier to use (11 versus 1) than beclomethasone dipropionate Rotahaler.. As a consequence of the difference in local potency of the steroids and the fact that Turbuhaler deposits more drug particles in the lung than Rotahaler, budesonide inhaled via Turbuhaler appeared to be a more effective steroid formulation than beclomethasone dipropionate inhaled via Rotahaler.

Topics: Asthma; Beclomethasone; Budesonide; Cross-Over Studies; Female; Humans; Male; Nebulizers and Vaporizers; Pregnenediones

The objective of this study was to determine the costs and effects of combined bronchodilator and anti-inflammatory therapy. In a 2.5-yr randomized controlled study, combined beta 2-agonist/corticosteroid therapy (BA + CS) and combined beta 2-agonist/anticholinergic therapy (BA + AC) were compared with beta 2-agonist/placebo therapy (BA + PL). Included in the study were 274 patients 18 to 60 yr of age with moderately severe obstructive airways disease. The main clinical endpoints were lung function, hyperresponsiveness, restricted activity days, and symptom-free days. The economic endpoints were the costs of health care utilization. Compared with BA + PL, BA + CS led to significant improvements in FEV1, PC20, and symptom-free days. BA + AC did not differ from BA + PL in this respect. The respective annual acquisition costs of BA + CS, BA + AC, and BA + PL were 532 US$, 277 US$, and 156 US$. Thus, BA + CS costs 376 US$ more than BA + PL. However, compared with BA + PL therapy, BA + CS led to statistically significant savings in other health care costs of about 175 US$ (95% CI from 46 to 303 US$). Thus, more than half of the additional costs of adding the inhaled corticosteroid are compensated for by a reduction in the costs of other health care services. Overall, inhaled corticosteroids lead to a small but net increase in health care costs of 201 US$ per patient per year.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asthma; Beclomethasone; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Terbutaline

Comparisons of relative potency for the three inhaled corticosteroids in the United States are limited to assessment of skin blanching.. Development of a method for comparing relative potencies of inhaled corticosteroids for topical effect on human airway and systemic effect.. With use of partial suppression of immediate response to inhaled allergen and 24-hour urinary free cortisol output, three-point dose-response curves were constructed for beclomethasone dipropionate (50 micrograms/puff), triamcinolone acetonide (100 micrograms/puff), and flunisolide (250 micrograms/puff). A randomized, parallel, single-blind study design was used. Dosing began with one puff four times a day for flunisolide and two puffs four times a day for the others. Doses were doubled after 1 week and again after a second week.. Twenty-five patients completed the study. Dose-response relationships were shown for each inhaled corticosteroid for both topical and systemic effect. Dose-response curves for the three preparations were similar when response was plotted against delivered dose in micrograms.. Within the limits of the assays, relative potencies of the three preparations appeared to be approximately equivalent for both topical and systemic effect when dose was expressed in micrograms. Relative potency per puff is therefore approximately proportional to the dose delivered. This method has potential for evaluation of relative potency of newer inhaled corticosteroids and the relative advantage of alternative delivery systems.

Topics: Administration, Inhalation; Administration, Topical; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Assay; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluocinolone Acetonide; Humans; Male; Single-Blind Method; Triamcinolone Acetonide

We retrospectively studied the use of inhaled corticosteroids in patients who experienced near fatal episodes (NFE) to determine whether such therapy reduces the risk of death. Forty-eight patients who had near fatal episodes of asthma between January 1981 and December 1989 were divided into two groups. Group A comprised 19 patients who received beclomethasone dipropionate (BDP) daily (mean dose of BDP:687 micrograms/day: 200-2,000) following NFE, and Group B, 28 patients who did not take BDP or who took less than 6 mg BDP/month. During the follow-up period (Group A:82.9 months, Group B:66.2 months), no patients in Group A died, but eight deaths occurred in Group B (mean period between near fatal episode and death was 31.5 months: 12-66). These results suggest that the regular use of inhaled corticosteroids, even at low doses, may reduce the risk of death in patients who experience NFE.

Topics: Acute Disease; Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Survival Analysis; Treatment Outcome

Relatively little is known about the influence of inhaled corticosteroids on general well-being (quality of life) in patients with asthma or COPD. In a 4-year prospective controlled study, we examined the influence of beclomethasone dipropionate (BDP), 400 micrograms, two times daily, on quality of life in 56 patients with asthma or COPD in comparison with the effects of BDP on symptoms and lung function. During the first 2 years, patients received only bronchodilator therapy with salbutamol or ipratropium bromide. During the third and fourth years, additional treatment with BDP was given. Fifty-six patients (28 with asthma, 28 with COPD) with an annual decline in the forced expiratory volume in 1 s (FEV1) of at least 80 mL/yr in combination with at least two exacerbations per year during bronchodilator therapy alone participated. Quality of life was assessed at the start and after 2 and 4 years by means of the Inventory of Subjective Health (ISH) and the Nottingham Health Profile (NHP). Although BDP significantly improved the course of lung function (FEV1)(p < 0.0001), it did not improve the ISH score or the six dimensions of the NHP neither in asthma nor in COPD. Beclomethasone dipropionate temporarily decreased respiratory symptoms during months 4 to 6 of BDP treatment in patients with asthma (p < 0.01) and during months 7 to 12 in patients with COPD (p < 0.05). A weak correlation was found both cross-sectionally and longitudinally between (change in) symptoms and quality of life on the one hand, and the (change in) FEV1 on the other. It was concluded that BDP did not improve the general well-being of patients with asthma or COPD as measured by these generic health instruments. However, BDP significantly improved the course of lung function and temporarily decreased the severity of symptoms. It seems probable that changes in quality of life would have been better detected by use of a disease-specific health instrument. Such an instrument was not available at the start of the study. Another possible explanation for these observations is that patients soon get used to different levels of lung function and learn to live with their disease. It is advised that disease-specific health instruments are used in future intervention studies and that quality of life is measured frequently during the early phase of the intervention, eg, once every month.

Topics: Administration, Inhalation; Albuterol; Asthma; Beclomethasone; Female; Forced Expiratory Volume; Health Status; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Prospective Studies; Quality of Life

Inhaled lysine acetylsalicylate and furosemide exert a mutually potentiating protective activity on experimentally induced bronchoconstriction in asthma.. Our purpose was to investigate the clinical effectiveness of combined treatment of asthma with inhaled lysine acetylsalicylate and furosemide.. We performed a randomized, double-blind, crossover study in nine patients with chronic asthma requiring a high dose (2 mg/day) of inhaled beclomethasone for clinical control. Patients were treated with a combination of 720 mg inhaled lysine acetylsalicylate and 40 mg furosemide twice daily, or with matched placebo in addition to inhaled steroids. The dose of inhaled steroids was reduced by half every 15 days and eventually suspended unless a patient's respiratory condition worsened.. During treatment with placebo, all patients had worsening of asthma at dosages of 1 or 0.5 mg/day beclomethasone (mean +/- SE, 833 +/- 83 micrograms/day). During combined treatment complete suspension of inhaled steroids in two patients and reduction to 0.5 to 0.25 mg in the remaining seven patients (mean, 250 +/- 72 micrograms/day) was achieved, with a mean reduction of 71% +/- 7%. Forced expiratory volume in 1 second, weekly peak expiratory flow rate, symptom score, and bronchodilator intake remained significantly better with combined treatment than with placebo.. Treatment with inhaled lysine acetylsalicylate and furosemide allows a considerable sparing of inhaled steroids without significant side effects in patients with severe asthma.

Topics: Administration, Inhalation; Adolescent; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Beclomethasone; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Furosemide; Humans; Lysine; Male; Middle Aged

Eighty six children with troublesome wheezing were studied, in a semiprospective clinical trial with the patients acting as their own controls, to assess the efficacy and cost effectiveness of inhaled steroids. Improvement in school attendance, hospitalisations, breakthrough wheezing, and acute severe attacks were used to assess clinical efficacy. Expenditure for the family, on a cost of illness framework, before and after treatment, was used to estimate cost effectiveness. Highly significant numbers of patients showed improvement in clinical parameters, confirming efficacy. Mean monthly cost before inhaled steroid treatment was Rs 2652.33 (36.33 pounds) and Rs 449.42 (6.16 pounds) after starting treatment. The mean cost per unit satisfaction (cost utility value) which was Rs 255.54 (3.50 pounds) before starting prophylaxis came down to Rs 5.42 (0.07 pound) after starting treatment. There are no previous reports of cost-benefit assessment of inhaled steroids in childhood asthma. It is concluded that, even for developing countries with financial constraints, inhaled steroid treatment for prophylaxis of asthma is a cost effective and rational form of treatment.

Topics: Administration, Topical; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Developing Countries; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Pregnenediones; Prospective Studies; Sri Lanka

Bloodspot cortisol, where finger pricked blood is applied to blotting paper, is suitable for repeated measurements in the home environment. The use of bloodspot cortisol measurements in children with asthma and the effect of inhaled corticosteroids on daytime cortisol concentrations were assessed. Twenty children with mild asthma were randomised to receive double blind either placebo or beclomethasone dipropionate 200 micrograms twice daily. Blood was taken by finger prick at home on waking, and treatment administered. Blood was then taken one hour after treatment, at lunchtime, and in the evening. The area under the curve (AUC) for the four time points was calculated as a composite index of daytime cortisol. Mean (SEM) bloodspot cortisols fell progressively over the day from 199.2 (15.6) nmol/l to 58.4 (8.9) nmol/l. Cortisol in the group treated with beclomethasone dipropionate was lower at all time points, but was significant only after treatment (mean (SEM) 120.9 (14.3) v 177.5 (21.0) nmol/l) and at lunchtime (mean (SEM) 82.7 (12.4) v 128.9 (12.6) nmol/l). AUC for the beclomethasone dipropionate treated group was also significantly decreased (mean (SEM) 317 (31.4) v 446 (29.7)). Beclomethasone dipropionate at a dose of 400 micrograms/day significantly suppresses the daytime cortisol profile.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Blood Specimen Collection; Child; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Patient Acceptance of Health Care; Pituitary-Adrenal System

Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.

Topics: Administration, Inhalation; Adrenal Glands; Asthma; Beclomethasone; Body Height; Child; Double-Blind Method; Female; Growth Disorders; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System

The effects of cessation of therapy with inhaled steroids on symptoms, lung function, and airway responsiveness in stable bronchial asthma should be examined.. During a 4-week run-in period 24 patients inhaled beclomethasone dipropionate (BDP) 2000 micrograms/d and salbutamol 800 micrograms/d. This was followed by a 6-week treatment period during which the patients obtained either placebo plus 800 micrograms salbutamol or 2000 micrograms BDP plus 800 micrograms salbutamol in a randomized double-blind design. Symptoms, lung function, and airway responsiveness to histamine were measured before and after the run-in period and at the end of each week during the treatment period.. Airway responsiveness was assessed as the concentration of inhaled histamine which caused a 20% fall in FEV1 compared to baseline (PC20). During the run-in period, 21 of the 24 patients showed an increase of PC20 (p = 0.0005). In the placebo group, 5 patients had to cease the protocol after 1 to 4 weeks of the treatment period because of intolerable symptoms and severe worsening of lung function; PC20 on entry was significantly smaller in these patients compared to those who completed the protocol (p = 0.01). After 6 weeks, FEV1 had decreased by 8.5% (p = 0.005) and PC20 by 1.71 doubling concentrations (p = 0.0003). In the BDP group, all patients completed the study and PC20 after the treatment period was significantly higher (p = 0.04) in the BDP than in the placebo group.. Our data suggest that patients on long-term inhaled steroid therapy with a high degree of bronchial hyperresponsiveness are more likely to show early deterioration of their clinical state after cessation of inhaled steroids.

Topics: Administration, Inhalation; Adult; Airway Resistance; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Long-Term Care; Male; Middle Aged; Substance Withdrawal Syndrome

Topics: Administration, Inhalation; Airway Resistance; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Double-Blind Method; Drug Therapy, Combination; Humans; Long-Term Care; Substance Withdrawal Syndrome

A group of 32 patients with moderately severe, chronic asthma (mean FEV1 55% of predicted), maintained on moderately high doses of inhaled corticosteroids (mean dose 1,100 micrograms/d), participated in this double-blind, placebo-controlled crossover study. The effect on pulmonary function of adding theophylline (U, once daily Uniphyl), inhaled salbutamol (S, 200 micrograms four times per day), and their combination (C) or placebo (P) was assessed on Day 14 of each treatment phase. Patients recorded peak expiratory flow, asthma symptom severity (morning and evening), and use of rescue salbutamol inhaler in daily diaries. Mean FEV1 between 0730 and 1800 h and maximum FEV1 between 0730 and 1300 h were significantly higher on U, S, and C compared with P (p < 0.006). Morning peak flow and FEV1 (0730 h) were significantly higher on U and C compared with S and P (p < 0.01). Evening peak flow was higher on U than P (p < 0.001), and C was higher than S and P (p < 0.01). Rescue salbutamol inhaler use was significantly higher on P than on U, C, or S (p = 0.0001). Patient rating of asthma symptoms during C was significantly better than on S or P (p < 0.05). Patient rating of asthma control and study phase preference was significantly higher on combination and Uniphyl alone than on placebo, the combination also being superior to salbutamol alone. Addition of Uniphyl or a combination of Uniphyl and salbutamol significantly improves pulmonary function and asthma symptoms in patients treated with high doses of inhaled corticosteroids and as-needed beta agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Pulmonary Ventilation; Theophylline

Osteoporosis is a well-known, serious complication of long-term high-dose corticosteroid therapy. This study was performed to determine the effects of commonly used doses of oral and inhaled steroids on biochemical indices of bone formation. Initially we examined the long-term effects of oral steroids. Thirty-four outpatients with symptomatic asthma or chronic obstructive airways disease (COAD) receiving long-term oral prednisolone (mean 10.1 mg daily) were compared with 34 control subjects with asthma or COAD matched individually for age, sex, and menopausal status who were not taking oral steroids. Plasma osteocalcin concentrations were significantly lower (patients 6.3 +/- 0.1 ng/ml; control subjects 8.6 +/- 0.5 ng/ml, mean +/- SEM; p < 0.01) in patients on steroids with no difference in alkaline phosphatase. To examine the short-term effects of oral and inhaled corticosteroids, healthy male volunteers were given a 7-d course of either 15 mg oral prednisolone daily (n = 10) or 500 micrograms inhaled beclomethasone twice daily (n = 20). After 1 wk of oral prednisolone, mean plasma osteocalcin decreased from 11.8 +/- 1.1 ng/ml to 6.9 +/- 0.8 ng/ml (p < 0.001). With inhaled beclomethasone mean plasma osteocalcin decreased from 11.6 +/- 0.6 ng/ml to 9.6 +/- 0.6 ng/ml (p < 0.001) with no change in alkaline phosphatase. In doses routinely prescribed for the prophylaxis and treatment of asthma, oral and inhaled steroids suppress osteocalcin levels and may therefore inhibit bone formation. This effect is seen with short courses of steroids and also with chronic administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Oral; Adult; Age Factors; Asthma; Beclomethasone; Bone Development; Cross-Sectional Studies; Female; Humans; Lung Diseases, Obstructive; Male; Matched-Pair Analysis; Middle Aged; Osteocalcin; Prednisolone; Prospective Studies; Sex Factors

A double-blind, cross-over protocol was applied to 22 asthmatic patients who were previously subjected to provocation tests with methacholine. The baseline FEV1 for mild asthma was 89.6 +/- 13.6% while for moderate asthma it was 73 +/- 6%. The initial provocation tests with methacholine revealed that the mild asthma group needed a greater accumulated dose of methacholine than that required by the moderate asthma group to lower the FEV1 by 20%, stressing the enhanced bronchial hyperreactivity present in the latter group. Significant differences in the PD20 values were obtained in both groups of patients using the combination of salbutamol plus beclomethasone. Salbutamol alone was ineffective to change the PD20 values in mild asthma while beclomethasone alone was able to change significantly the PD20 values in these patients, stressing the importance of the inflammatory component in the pathogenesis of stable asthma. Furthermore, the combination of both drugs was also more effective in the moderate asthma group than either medication alone, confirming the pharmacological control of the obstructive and inflammatory changes that are already established in patients with moderate asthma.

Topics: Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Child; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Spirometry

The present study was set up to investigate whether salmeterol in children with asthma already treated with inhaled corticosteroids (ICS) leads to a sustained bronchodilator effect and decreased bronchial responsiveness, both during the day and night. Furthermore, we investigated whether cessation of salmeterol leads to a rebound increase in bronchial responsiveness. Forty children with asthma (aged 7-15 yrs) using ICS participated in a randomized, double-blind, parallel study. They received either twice daily 50 micrograms salmeterol or placebo. FEV1 and provocative concentration of methacholine that caused a 20% fall in FEV1 (PC20) were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk. The same measurements were performed at 4:00 P.M. at 8 h after the first dose, and after 1 and 8 wk. After cessation of the study drug, FEV1 and PC20 were measured at 12 and 20 h and after 1 wk. Overall mean FEV1 from 1 to 16 wk of treatment was significantly higher in the salmeterol group than in the placebo group (difference, 4.9 +/- 2.0%, p = 0.01). Evolution in time of FEV1 did not differ significantly between the two groups (p = 0.09). Overall mean PC20 from 1 to 16 wk of treatment was not significantly higher with salmeterol than with placebo (difference, 0.7 +/- 0.4 doubling dose [DD] p = 0.07); evolution in time of PC20 did not differ significantly between the two groups (p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adolescent; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Child; Circadian Rhythm; Double-Blind Method; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Salmeterol Xinafoate

We studied the usefulness of 24 weeks of therapy with inhaled beclomethasone dipropionate (BDP) in the management of mild and moderately severe asthma in adults. To determine the optimal dose and treatment duration, the patients were divided into three groups. Patients in group I (n = 10) were treated with bronchodilators but no BDP. Patients in group II (n = 12) received bronchodilators and 450 micrograms/day of BDP. Patients in group III (n = 17) received bronchodilators and 900 micrograms/day of BDP. BDP was inhaled via a large spacer (Volumatic). Asthma scores were measured before treatment began, and again every 2 weeks for the duration of the study (26 weeks). Peak expiratory flows (PEF) were measured before treatment began, 2 weeks after treatment had begun, and again every four weeks until the end of the study. Vital capacity, FEV1, and bronchial reactivity to methacholine were measured before treatment began, and again 12 weeks and 24 weeks after it had begun. Adrenocortical function in patients in group III was measured with a rapid ACTH test, at the same time as the pulmonary functions were measured. The results were: 1) Asthma scores decreased more in patients who received the higher dose of BDP than in those who received the lower dose, especially during the second 12 weeks. 2) After two weeks of treatment, %PEF had increased significantly in both groups that received BDP, but after six weeks of treatment there was no further improvement. %PEF did not improve in the group given bronchodilators only. 3) In the patients whose baseline %PEF was less than 80%, only the higher dose of BDP significantly increased %PEF. 4) Only the higher dose of BDP increased the %VC, the FEV1%, and the PD20 for methacholine. 5) Asthma type and severity were not related to the usefulness of BDP therapy. 6) Results of the rapid ACTH test indicated that the higher dose of BDP did not suppress adrenocortical function. These data indicate that 900 micrograms of BDP per day is more effective than 450 micrograms/day as initial therapy for long-term management of mild or moderate asthma in adults, and that the dose of BDP should be reviewed after 3 months of treatment. Patients in whom asthma is well-controlled may tolerate a reduction in dose, and those in whom asthma is not well-controlled may require a higher dose.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged; Time Factors

To assess bone and collagen turnover in asthmatic children treated with dry powder budesonide from the Turbuhaler and dry powder beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day.. Thirteen prepubertal children with asthma.. Open crossover study with two treatment periods and treatment free run-in and wash-out periods. All periods were of two weeks' duration. At day 14 in each period blood samples were taken for assessment of serum osteocalcin, the carboxyterminal propeptide of type I collagen (PICP), and the aminoterminal propeptide of type III collagen (PIIINP). At the same time urine was collected for assessment of creatinine corrected pyridinoline (uPYR/cr) and deoxypyridinoline (udPYR/cr) crosslinks.. Osteocalcin concentrations were not influenced by any of the treatments. During budesonide treatment mean (SEM) PICP was reduced by 18% (8%) (p = 0.03), PIIINP by 24% (3%) (p = 0.0002), uPYR/cr by 16% (6%) (p = 0.03), and udPYR/cr by 21% (13%) (p = 0.12). During treatment with beclomethasone dipropionate mean (SEM) PICP was reduced by 20% (6%) (p = 0.01), PIIINP by 36% (3%) (p = 0.0002), uPYR/cr by 18% (4%) (p = 0.004), and udPYR by 13% (5%) (p = 0.02). The suppressive effect of beclomethasone dipropionate on PIIINP was more marked than that of budesonide (p = 0.001).. Treatment with dry powder budesonide and beclomethasone dipropionate 800 micrograms/day is associated with suppression of bone and collagen turnover. The suppression seems to be more marked during treatment with beclomethasone dipropionate. Long term effects and effects of lower doses of budesonide and beclomethasone dipropionate on bone and collagen markers needs further study.

Topics: Administration, Inhalation; Administration, Topical; Amino Acids; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Budesonide; Child; Collagen; Cross-Over Studies; Female; Glucocorticoids; Humans; Male; Osteocalcin; Peptide Fragments; Powders; Pregnenediones; Procollagen

The role of airway inflammation in the pathogenesis of asthma in childhood is uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA) in the previous 12 months, performed a methacholine challenge and exercise test on separate days at monthly intervals. The subjects had not received oral or inhaled corticosteroids for 12 months prior to the study. The dose-response relationship to inhaled methacholine was expressed as the cumulative dose provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following maximal exercise. Following the first methacholine challenge and exercise test, the children were randomized in a double-blind manner to receive inhaled beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or a placebo b.i.d. from a Diskhaler for 3 months. All children were asymptomatic at the time of testing, and there was no significant change in the baseline FEV1 of any subject prior to either challenge throughout the study period. When compared to placebo, the bronchial responsiveness to exercise and methacholine was significantly attenuated in the children who had received inhaled BDP for at least 1 month. There was no relationship between the bronchial responsiveness to methacholine and exercise. There was no significant difference in the bronchial responsiveness to either stimulus in the atopic and nonatopic children. The results of this study suggest that immunoglobulin E (IgE)- and non-IgE-mediated airway inflammation are important in exercise- and methacholine-induced bronchoconstriction in children with recurrent wheeze, although it is probable that different mechanisms are responsible.

Topics: Administration, Inhalation; Administration, Topical; Analysis of Variance; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Asthma, Exercise-Induced; Beclomethasone; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Double-Blind Method; Exercise; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Prospective Studies; Recurrence; Respiratory Mechanics; Respiratory Sounds

This study compared the efficacy and tolerability of sodium cromoglycate (SC) and beclomethasone dipropionate (BDP) in adult patients with bronchial asthma inadequately treated with bronchodilators alone. The study was a double-blind, randomized, double-dummy, parallel-group study. Patients with mild to moderate symptomatic asthma, inadequately treated with bronchodilators only, were, after a 2-week run-in (base-line) period, randomized to 8 weeks of treatment with either SC 10 mg four times daily or BDP 100 micrograms four times daily. Salbutamol metered-dose inhaler was given as relief medication. A total of 37 patients were randomized for treatment, 19 patients in the SC group and 18 patients in the BD group. Efficacy and safety were determined by daily record card data: morning and evening peak-expiratory-flow rates (PEFR), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, as were the physician's and the patient's assessment of the medication at the end of the study. The safety and tolerability of the trial medication were assessed by monitoring adverse events throughout the study. A clinically and statistically significant improvement of the asthma in FEV1, symptom scores, rescue medication, and global opinion of efficacy was observed, and both groups provided equivalent efficacy. The morning PEFR as well as the evening PEFR for both groups improved, but was statistically significant only for the BDP group (M-PEFR). Both drugs were well tolerated with only a few minor adverse events. This trial shows that SC and BDP are equally effective anti-inflammatory treatments for mild to moderate bronchial asthma in adults.

Topics: Adult; Asthma; Beclomethasone; Cromolyn Sodium; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988-90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler. Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990-2 every third month as long as the patients remained symptom-free and without significant decreases in FEV1 or PEF. In group A, the maintenance dose could be reduced from 1003.9 +/- 325.4 micrograms BDP (mean +/- SD) to 602.9 +/- 454.4 micrograms budesonide Turbuhaler (P < 0.001). In group B, no significant dose reduction was possible; the mean dose was +/- SD 1067.3 +/- 36.6 micrograms in 1990, and 1019.2 +/- 324.7 micrograms in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.

Topics: Adrenergic beta-Agonists; Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Pregnenediones; Spirometry

We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Depression, Chemical; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Vital Capacity

Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Bronchi; Double-Blind Method; Eosinophils; Epithelium; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-8; Male; Middle Aged

Twenty-four steroid-dependent intractable asthmatics were treated with oral prednisolone (PSL) (basic dose) + additional PSL and oral PSL (basic dose) + inhaled beclomethasone (BDP) alternately, to assess the clinical symptoms in each administration period. Equivalent doses of PSL to BDP were calculated. 1. Peak expiratory flow rate (PEF) during additional administration of BDP was markedly higher both in the morning and at night compared with that during additional administration of BDP was markedly higher both in the morning and at night compared with that during additional administration of PSL (p < 0.01 and p < 0.05 respectively). 2. The relation between additional doses of either PSL or BDP and attack scores was analysed in regression to obtain a dose equivalence line. 3. BDP 400 micrograms was equivalent to PSL 7.04 mg on average. 4. The equivalent dose of PSL to BDP tended to be lower in cases where the period of dependency on oral steroids was longer, the basic dose was larger, or the asthma was more severe. These data indicate that the application of inhaled steroids may be useful in the therapeutic management of steroid-dependent intractable asthmatics.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Asthma; Beclomethasone; Drug Therapy, Combination; Female; Humans; Japan; Male; Middle Aged; Prednisolone

Clinical experiences have suggested distinct differences in responses to anti-asthmatic drugs between patients suffering early morning asthmatic attacks and those experiencing nocturnal ones. However, there has been no report on any difference in the improvement of asthmatic flow dipping after inhaled and/or oral steroid treatment. In this retrospective study, the peak expiratory flow rates (PEF), which had been monitored four times a day, were reviewed in 40 chronic asthmatics. The group consisted of 19 patients with very low PEF (geometrical mean PEF/week [mPEF] < 60% of the personal best PEF), 15 patients with moderately low PEF (mPEF 60% to 70% of personal best PEF), 2 patients with mildly low PEF (mPEF 70% to 80% of personal best PEF) and 4 patients with occasionally low PEF (mPEF > 80% of personal best PEF). Of 40 chronic asthmatics, 22 patients had morning dipping alone and 10 patients had both morning dipping and nocturnal dipping. After inhaled and/or oral steroid treatment at sufficient level, mPEF was improved in all patients. All the dipping disappeared except for morning dipping in five cases. We concluded that there was a difference in responses to inhaled and/or oral steroids during early morning dipping and during nocturnal dipping in chronic asthmatics. There should be further investigation to discriminate between pathophysiological events that may be related to morning dipping and to nocturnal dipping.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Asthma; Beclomethasone; Chronic Disease; Circadian Rhythm; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Retrospective Studies

We examined HPA axis function using a short tetracosactrin test in 94 asthmatics treated with three different modalities. The first group, (B + S), consisted of 41 patients taking BDP (910 +/- 320 micrograms, daily) plus a short term burst of oral steroids (20-40 mg daily, 3-7 days/course, 1-18 courses/year). The second group, (B + R), consisted of 19 patients taking BDP (1076 +/- 410 micrograms, daily) plus continuous oral steroids (2.5-20 mg/day for 1.8-24 years). The third group, (B alone), consisted of 34 patients taking BDP only (615 +/- 258 micrograms, daily). All patients had been inhaling BDP for more than 1 year. The rise in cortisol in response to tetracosactrin in B + S, B + R, and B alone was 12 +/- 4.3 micrograms/dl, 7.0 +/- 5.0 micrograms/dl and 14 +/- 4.5 micrograms/dl, respectively, and achieved cortisol was 21 +/- 4.5 micrograms/dl, 12 +/- 7.2 micrograms/dl and 23 +/- 4.2 micrograms/dl;, respectively. Both values were significantly lower in the B + R group than in either B + S or B alone. However, there was no difference between B + S and B alone, although the BDP dose was significantly larger in the B + S group. Significant HPA axis suppression (rise in cortisol < 7 micrograms/dl and achieved cortisol < 18 micrograms/dl) was seen in 7 patients. Although HPA axis suppression was more frequently seen in B + R (10/19), no significant difference was seen between B + S and B alone (4/41 and 1/34, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Function Tests; Adrenocorticotropic Hormone; Adult; Aged; Asthma; Beclomethasone; Drug Therapy, Combination; Female; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisolone

The increased use of high dose inhaled steroid in the treatment of asthma has revealed the risk of dose-dependent side effects. Nedocromil sodium is a non steroidal agent with anti-inflammatory properties.. To demonstrate whether nedocromil sodium may have some therapeutic benefit in asthmatic patients treated with high dose inhaled steroids and whether it has an inhaled steroid sparing effect.. 134 adults with moderate to severe asthma not adequately controlled with high dose inhaled steroids (750 to 1,500 micrograms/day).. After a two week baseline period, patients were randomized to receive either nedocromil sodium (4 mg qid) or placebo for 24 weeks in a double blind fashion. During the first 12 weeks of treatment, the dose of inhaled steroid was maintained constant whereas it was altered during the last 12 weeks according to asthma scores.. Among 108 patients reaching the reduction phase, a decrease of 250 micrograms of inhaled steroid or more was possible in 79% of patients on nedocromil sodium and in 60% of patients on placebo (p < 0.03). Symptoms scores were improved on both treatments during the 12 first weeks, more on nedocromil sodium than on placebo, treatment difference reaching significance for daytime asthma (p < 0.02). FEV1 improved during the trial for patients on nedocromil (from 69 +/- 18% to 74 +/- 21%; p < 0.005) whereas it did not for those on placebo.. Nedocromil sodium is effective in improving moderate to severe asthma in addition to inhaled steroid and has some steroid sparing effect in patients treated with high dose inhaled steroid.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nedocromil; Severity of Illness Index

Treatment of 21 steroid-dependent asthmatic patients with methotrexate (MTX) 15 mg/week was prospectively evaluated for a mean of 14.7 (SD 3.7) months. Before MTX, therapy consisted of a mean prednisone dose of 16.6 (SD 9.2) mg, in addition to inhaled beclomethasone/budesonide (mean daily dose 1157 (SD 330) micrograms) and bronchodilators. Thirteen patients were weaned from all regular systemic steroid therapy, a 50% or more reduction was achieved in four patients, and a less than 50% reduction in four patients. Abnormal liver function tests were noted in six of the 21 patients; this resolved despite continuation of MTX in five. In one patient, MTX was stopped because of symptoms as well as a fivefold rise in serum transaminases, and a speedy resolution was noted. Gastrointestinal side-effects were reported in six patients but were resolved in five with intramuscular MTX. There were no hematologic or pulmonary complications. We conclude that MTX appears to be both safe and efficacious as a steroid-sparing agent in most steroid-dependent asthmatic patients when taken over a long period.

Topics: Adult; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Liver; Liver Function Tests; Male; Methotrexate; Middle Aged; Prednisone; Pregnenediones; Prospective Studies; Time Factors; Treatment Outcome

Despite effective treatments, the morbidity and mortality of obstructive airways disease (asthma and COPD) remains high. Home monitoring of peak expiratory flow (PEF) is increasingly being advocated as an aid to better management of obstructive airways disease. The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups.. Patients aged 18-60 years were selected with PC20 < or = 8 mg/ml and FEV1 < 95% confidence interval of predicted normal. They were randomised to receive, in addition to a beta 2 agonist, either an inhaled corticosteroid (BA+CS), an anticholinergic (BA+AC), or a placebo (BA+PL). One hundred and forty one of these subjects with moderately severe obstructive airways disease completed seven periods of two weeks of morning and afternoon PEF measurements at home during 18 months of blind follow up.. Improvements in PEF occurred within the first three months of treatment with BA+CS and was subsequently maintained: the mean (SE) increase in morning PEF was 51 (8) l/min in the BA+CS group compared with no change in the other two groups. Similarly, afternoon PEF increased by 22 (7) l/min. Diurnal variation in PEF (amplitude %mean) decreased from 18.0% to 10.2% in the first three months of treatment with BA+CS. Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative (median rho-0.40) but with a large scatter. Relations between diurnal variation in PEF and changes in symptom scores, FEV1, and bronchodilator response were even weaker.. In patients with moderately severe obstructive airways disease, PEF rates and variation are greatly improved by inhaled corticosteroids. Since the relation of diurnal PEF variation with PC20, symptoms, FEV1, and bronchodilator response were all weak, these markers of disease severity may all provide different information on the actual disease state. PEF measurements should be used in addition to the other markers but not instead of them.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Circadian Rhythm; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Peak Expiratory Flow Rate; Terbutaline

Inhaled steroids are currently the first-line treatment of chronic asthma. Because each metered dose of beclomethasone dipropionate (BDP) is small (50 micrograms), short term burst or continuous use of oral steroids are combined in moderately to severely asthmatic patients. The effect of these treatments on bone metabolism remains unclear. Bone mineral density (BMD), osteoclacin (OC), PTH, Ca, and ALP were assessed in 130 asthmatic patients. There were 3 groups: the first group [B+R] consisted of 17 patients taking BDP (1190 +/- 536 micrograms/day) and also taking oral steroids (8.0 +/- 3.8 mg/day, 8.11 +/- 5.52 years), the second group [B+S] had 35 patients taking BDP (885 +/- 320 +/- g/day) and short-term bursts of oral steroids (PSL 20-40 mg/day, 3-7 days/course, 7.51 +/- 4.54 courses/year) and the third group [B alone] consisted of patients who were taking BDP (480 +/- 260 micrograms/day) alone. BMD was measured by dual energy X-ray absorptiometry (DEXA). In the [B+R], [B+S], and [B alone] groups, the BMD of vertebra (L1-4) was 0.75, 0.86, and 0.90 g/cm2, respectively. The percentages of predicted values based on age and sex were 92.0, 102.7, and 106.9% respectively. BMD and percent decrease were significantly lower in the [B+R] group than in the [B+S] or [B alone] group. It is likely that this phenomenon is caused by long-term use of oral steroids rather than by BDP inhalation but there is no significant difference between the [B+S] and the [B alone] groups. Daily BDP dose did not correlate with BMD by multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Asthma; Beclomethasone; Bone and Bones; Bone Density; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteocalcin; Prednisolone

Guidelines on asthma management recommend that in patients who still have symptoms on treatment with low-dose inhaled corticosteroids the first step should be an increase in inhaled corticosteroid dose. The addition of long-acting inhaled beta 2-adrenoceptor agonists is another option. We have compared these two strategies in a randomised, double-blind, parallel-group trial. We studied 429 adult asthmatic patients who still had symptoms despite maintenance treatment with 200 micrograms twice daily inhaled beclomethasone dipropionate (BDP). 3 did not provide verifiable data. Of the others, 220 were assigned salmeterol xinafoate (50 micrograms twice daily) plus BDP and 206 were assigned higher-dose BDP (500 micrograms twice daily) for 6 months. The mean morning peak expiratory flow increased from baseline in both groups, but the increase was greater in the salmeterol/BDP group than in the higher-dose BDP group at all time points (differences 16-21 L/min, p < 0.05). Mean evening PEF also increased with salmeterol/BDP but not with higher-dose BDP. There were significant differences in favour of salmeterol/BDP in diurnal variation of PEF (all time points) and in use of rescue bronchodilator (salbutamol) and daytime and night-time symptoms (some time points). There was no significant difference between the groups in adverse effects or exacerbations of asthma, indicating that in this group of patients regular beta 2-agonist therapy was not associated with any risk of deteriorating asthma control over 6 months. This study suggests a need for a flexible approach to asthma management.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Asthma; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Respiratory Mechanics; Salmeterol Xinafoate

Fifty-five asthmatics, previously treated with inhaled steroids (mean age 48 years, range 16-68 years, mean duration of the disease 10 years, range 1-35 years) participated in this multicentric 2-phase trial. The patients were in good clinical condition (basal FEV1 3.02 litres (1.38-6.29), 90% (48-131%) of predicted values; mean (range)). In the first phase (randomized, double-blind crossover study) 2 beclomethasone dipropionate (BDP) inhalation aerosol preparations (MDI) were administered through collapsible spacer. In the second phase (open, randomized, parallel group comparison), 1 of the preparations was administered via collapsible and the other via traditional large volume spacer. The total daily dose of inhaled beclomethasone was 1,000 micrograms. The evaluation of efficacy was based on peak flow monitoring (PEFR) carried out at home twice daily and on FEV1 measured in spirometry at control visits after the run-in period and after each 4-weeks treatment period. Side-effects and asthma symptoms were recorded on patient diaries. The patients were asked to evaluate the treatment efficacy and the use and handling of the MDI-spacer combinations with Visual Analog Scale (VAS) at the end of each treatment period. No statistically significant differences were found in PEFR or FEV1 between the treatments during whole study. The asthma symptom scores were low as well as the use of concomitant inhaled sympathomimetics which indicates good and equal efficacy of the preparations. The MDI-spacer combinations were equally well tolerated. According to the VAS scores, the collapsible spacer was easier to use and statistically significantly easier to handle than traditional large volume spacer.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Double-Blind Method; Excipients; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Salbutamol alone (400 micrograms per day) or salbutamol together with beclocort (1 mg per day) was used in 20 patients with mild asthma. 12 patients received during a month salbutamol combined with nedocromil (Tilade 8 mg per day). Prior starting treatment and after concluding a histamine provocation challenge was performed allowing to assess the bronchodilating properties of salbutamol. We conclude that: salbutamol alone produced a statistically nonsignificant increase of bronchial hyperactivity; a combination of salbutamol with beclocort or nedocromil did not increase the bronchial hyperactivity; during the three month trial with salbutamol alone or in a combination with a antiinflammatory agent the bronchodilatatory effect of salbutamol remained the same.

Topics: Adult; Albuterol; Asthma; Beclomethasone; Bronchial Hyperreactivity; Drug Therapy, Combination; Female; Humans; Male; Nedocromil; Treatment Outcome

Inhaled steroids are the mainstay in the antiinflammatory treatment of asthma. In the last few years, these agents have been used in increasing doses. Because high doses of inhaled steroids can reduce serum osteocalcin levels, there are concerns regarding their long-term effects on bone metabolism.. We examined the effects of doses of 800 micrograms/day or greater of beclomethasone or budesonide for more than 18 months in 37 asthmatic subjects (group A), matched to a control group of 37 asthmatic subjects using little or no inhaled steroids (< 500 micrograms, group B). All had a clinical evaluation, measurements of expiratory flows, and determination of serum creatinine, calcium, phosphate, gamma-glutamyl transpeptidase, alkaline phosphatase, cortisol, and osteocalcin levels. A 2-hour urinary sample was obtained for creatinine, calcium, phosphate, hydroxyproline, and cortisol measurements. Bone density was assessed at the lumbar spine level and at the hip with a Hologic-QDR-2000 osteodensitometer (Hologic, Boston, Mass.).. The mean (+/- SD) daily dose of inhaled steroids over the last 2 years was 1140 +/- 353 micrograms in group A (mean duration of use of > 800 micrograms/day, 34.2 +/- 13.0 months) and 89 +/- 98 micrograms for group B (mean duration of use of < 500 micrograms/day, 15.7 +/- 18.8 months). The number of oral steroid treatments (< 15 days) during the last 2 years was small in the two groups, 0.92 +/- 1.27 in group A and 0.05 +/- 0.23 in group B (p > 0.05). The only differences between our two groups in terms of serum or urinary parameters were for mean osteocalcin level, which was lower in group A (2.16 +/- 1.09 ng/ml) than in group B (2.70 +/- 0.98 ng/ml) (p = 0.029), and in mean urinary phosphorous level, which was higher in group A (1.44 +/- 0.76 mmol/2 hr) than in group B (1.26 +/- 0.89 mmol/2 hr (p = 0.034). Mean urinary hydroxyproline levels were 15.51 +/- 6.98 mumol/2 hr in group A and 13.53 +/- 7.13 mumol/2 hr in group B (p > 0.05). Mean mineral bone densities of the lumbar spine and hip were similar in the two groups with values of 0.923 +/- 0.136 gm/cm2 and 0.719 +/- 0.147 gm/cm2 in group A and 0.933 +/- 0.154 gm/cm2 and 0.694 +/- 0.095 gm/cm2 in group B (p > 0.05). The T and Z scores for lumbar spine were -1.32 +/- 1.22 and -0.85 +/- 1.02 in group A and -1.19 +/- 1.33 and -0.72 +/- 1.08 in group B (p > 0.05). There was no correlation between the duration or dose of steroid use and bone density or osteocalcin. Although the serum osteocalcin level was lower in the group of subjects using high-dose inhaled steroids, suggesting an osteoblastic depression, bone density was not significantly different compared with the control group.. This study shows that although the serum osteocalcin level was lower and the urinary phosphorus level was higher in subjects using high-dose inhaled steroids for a mean of 34 months, compared with a control group, no significant difference in bone density or other markers of bone metabolism was found between the two groups.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bone Density; Bronchodilator Agents; Budesonide; Calcium; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Time Factors; Vital Capacity

The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Basement Membrane; Beclomethasone; Biopsy, Needle; Bronchi; Bronchoalveolar Lavage Fluid; Cell Count; Collagen; Double-Blind Method; Eosinophils; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Mast Cells; Middle Aged; T-Lymphocyte Subsets

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Eosinophils; Female; Humans; Leukocyte Count; Leukotriene C4; Male; Methacholine Chloride

Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain.. Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment.. In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids.. No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bone and Bones; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; Lung Diseases, Obstructive; Male; Osteocalcin; Peptide Fragments; Pregnenediones; Procollagen

A total of 261 patients with symptomatic, mild to moderate asthma were randomized to treatment in this 4-week, double-blind, parallel-group comparison of fluticasone propionate 200 micrograms/d with beclomethasone dipropionate 400 micrograms/d. Improvements from both treatments were seen in diary card data. Morning peak expiratory flow rate (PEFR) improved from 375 to 390 and 371 to 382 l/min with fluticasone propionate and beclomethasone dipropionate, respectively. Symptom scores, percentage of symptom-free days and nights, and use of rescue beta 2-agonist medication also improved, as did clinical lung function. With the exception of percentage of rescue-free days, which was greater for beclomethasone dipropionate, none of the differences between the groups were statistically significant. There was a significant difference between treatments in the number of rescue-free days over days 1-28; however, there was no difference between treatments in the number of rescue-free days over days 1-14, nor was there any difference in the number of inhalations of rescue medication used throughout the study. Very few adverse effects were reported. Although all mean plasma cortisol values were within the normal range, they were significantly different between treatments, rising from 402 to 429 nmol/l with fluticasone propionate, and falling from 435 to 394 nmol/l with beclomethasone dipropionate (P = 0.006). Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate (P = 0.024). In conclusion, fluticasone propionate 200 micrograms/d is as effective as beclomethasone dipropionate 400 micrograms/d with less effect on plasma cortisol levels.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Injections; Male; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

Glucocorticosteroids are widely used as drugs of first choice in the treatment of moderate to severe asthma. The effects of inhaled steroids in high doses have been compared with oral prednisone in asthmatic patients in a double blind crossover study.. The trial consisted of a two week run in period followed by two four week treatment periods separated by a four week washout. During the treatment period patients took either 1000 micrograms beclomethasone dipropionate twice daily and placebo tablets once daily, or 10 mg prednisone daily in one morning dose and placebo inhaler twice daily. The effects of treatment on the provocative dose of histamine producing a 20% fall in FEV1 (PC20 histamine), peak flow measurements at home, and spirometric measurements in the clinic, as well as on the basal and stimulated plasma cortisol levels were measured.. Seventeen patients with asthma completed the study. After four weeks of treatment beclomethasone dipropionate showed a significantly better effect on morning peak expiratory flow rate than prednisone. There was a trend to a greater improvement in the PC20 histamine in patients receiving beclomethasone dipropionate than in those receiving prednisone. There were no significant differences in spirometric values, symptom scores, or basal and stimulated cortisol levels between the treatments. The within treatment analysis showed a significant effect of prednisone on stimulated cortisol levels but not of beclomethasone dipropionate.. Beclomethasone dipropionate 1000 micrograms twice daily has a slightly greater therapeutic effect in this population of asthmatic patients than 10 mg of prednisone once a day with less effect on adrenocortical function.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisone

Platelet-activating factor (PAF) may be a major mediator of asthma and bronchial hyperreactivity through its many proinflammatory actions. Specific antagonism of PAF might offer an alternative anti-inflammatory treatment to inhaled corticosteroids. To test this, we have studied the effect of an orally active PAF antagonist, WEB 2086, on the inhaled steroid requirements of symptomatic atopic asthmatics in a double-blind randomized placebo-controlled parallel group study. The inhaled corticosteroid dose required for symptomatic control of asthma was established and further steroid reduction was attempted after treatment with WEB 2086 40 mg three times daily for 12 wk. Of 106 patients recruited, 68 entered the treatment phase and 65 completed 6 wk of treatment. The mean daily corticosteroid dose (SE) at study entry was 1,257 (75) micrograms which was reduced by 323 (66) micrograms during the run-in period without loss of symptomatic control. A further 416 (57) micrograms reduction in inhaled corticosteroid dosage was possible during the treatment phase but this was almost identical in the WEB 2086 and placebo-treated groups, amounting to 353 (92) and 481 (65) micrograms/day respectively (not significant [NS]). Rate of relapse following corticosteroid reduction was a continuous variable and relapse occurred at different times depending on the variable used to define it. Time to relapse measured by an increase in symptoms correlated with disease duration (r = 0.41, p < 0.01) and with the dose of inhaled corticosteroid at study entry (r = 0.36, p < 0.01) but no other measured variable predicted the time to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Albuterol; Asthma; Azepines; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Platelet Activating Factor; Triazoles

In the treatment of stable mild to moderate asthma, twice-daily administration of inhaled steroids may allow adequate control of the asthma; however, comparisons of the efficacy of once- or twice-daily administration brought contradictory results. This study is a randomized, double-blind crossover trial, set to determine if inhaled beclomethasone dipropionate given once daily in the late afternoon or at bedtime can be as effective as a twice-daily regimen in the treatment of moderate asthma.. Subjects were randomly assigned to 3 different dosing regimens of inhaled beclomethasone: (1) regimen A, a twice-daily dose of 500 micrograms in the morning and at bedtime; (2) regimen B, a single dose of 1,000 micrograms in the late afternoon; and (3) regimen C, a single dose of 1,000 micrograms at bedtime.. Enrolled in the study were 42 subjects who required 500 micrograms of inhaled beclomethasone dipropionate twice daily to control symptoms of asthma and to minimize use of beta 2-adrenergic agonists, according to criteria suggested in a recent international consensus on asthma therapy. Prior to receiving therapy with inhaled steroids, all of these patients either had chronic symptoms of asthma that required administration of a short-acting beta 2-agonist at least twice per day, or had nocturnal asthma symptoms at least once per week.. After a 2-week baseline evaluation, each subject was given the 3 treatment regimens in randomized order, each for a period of 4 weeks. Subjects were asked to record daily symptoms of asthma and peak expiratory flows in the morning and evening. At the end of each treatment period, spirometric data and airway responsiveness to methacholine were measured.. Thirty-seven subjects completed the study. No significant difference was found among the 3 treatment regimens for asthma symptoms, FEV1, the provocative concentration of methacholine causing a 20 percent decrease in the FEV1 (PC20) (geometric means, 1.41, 1.09, and 1.09 mg/ml), and mean morning and evening peak expiratory flow rates (PEFR). The plasma cortisol level and the adrenocorticotropic hormone (ACTH) response were not significantly different among treatments, nor were side effects, which were minimal.. In moderate asthma controlled with a twice-daily dose of inhaled beclomethasone, a single total daily dose administered in the late afternoon or in the evening provides as good control of asthma for 2 months.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Adult; Aerosols; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate; Time Factors

The physiopathology of chronic cough remains obscure. We evaluated the possibility that chronic cough in nonasthmatic subjects is associated with airway inflammation, and if this is so, what the relationship between this inflammation and the possible etiology of cough might be, as well as its response to inhaled steroids. Nineteen nonsmoking, nonasthmatic subjects referred for a persistent cough (mean: 3.8 yr) were evaluated and compared with 10 normal subjects. The evaluation included a respiratory questionnaire, a physical examination, allergy skin-prick tests, chest and sinus radiographs, esophageal pH monitoring, measurements of expiratory flows, methacholine and citric acid challenges, and flexible bronchoscopy for bronchoalveolar lavage (BAL) and bronchial biopsies. Fourteen subjects further accepted participation in a randomized, double-blind crossover trial of inhaled beclomethasone (500 micrograms four times daily) and a placebo for 1 mo each. Four groups of subjects were identified according to the presence of postnasal discharge (n = 4), gastroesophageal reflux (n = 6), both conditions (n = 5), or neither (n = 4). Subjects with chronic cough had an increased number of inflammatory cells in their bronchoalveolar lavage fluid (BALF), but there was no significant difference between the four subgroups of coughers. As compared with control subjects, the bronchial biopsies of subjects with chronic cough showed increased epithelial desquamation (p = 0.004) and inflammatory cells (p = 0.005), particularly mononuclear cells (p < 0.01), in addition to submucosal fibrosis, squamous-cell metaplasia, and loss of cilia. These findings were not significantly different between the different etiologic groups. In subjects with chronic cough, basement-membrane thickness was normal and not different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asthma; Beclomethasone; Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Cough; Double-Blind Method; Female; Humans; Male

The prevalence of posterior subcapsular cataracts in young patients receiving inhaled glucocorticoids for treatment of chronic asthma is unknown. In a cross-sectional study, slit-lamp examinations were done on 95 consecutive young patients who were taking inhaled beclomethasone or budesonide. No posterior subcapsular cataracts were found. The median age of the patients was 13.8 (range 5.8-24.8). The median dose of inhaled beclomethasone or budesonide was 750 micrograms/day (range 300-2000), or 12.9 micrograms/kg per day (range 7.5-34.2). The median duration of treatment was 5 years (range 1-15). 77% of the patients had not used oral glucocorticoids in the year preceding the examination. This study suggests that routine screening for posterior subcapsular cataracts in this patient population is not warranted.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cataract; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Female; Humans; Male; Manitoba; Patient Compliance; Pregnenediones

In the day to day care of obstructive airways diseases (asthma and chronic obstructive pulmonary disease) important decisions such as disease classification and choice of therapy are based on assessment of the bronchodilator response. However, surprisingly little is known of the long term course of the bronchodilator response in patients with obstructive airways disease.. Data from a multicentre trial were used in which 274 patients aged 18-60 years with airways obstruction were selected with PC20 < 8 mg/ml and FEV1 < 95% CI of predicted. FEV1 was measured before and 20 minutes after 1000 micrograms terbutaline and 40 minutes after an additional 80 micrograms ipratropium bromide. Data were analysed from 185 patients who were followed up for 21 months (five measurements). Four different expressions of bronchodilator response (BDR) were examined for change under long term therapy, long term variability, and prognostic value in predicting response to inhaled corticosteroids.. There was a significant reduction in BDR of 117 ml after three months of treatment with a beta 2 agonist plus a corticosteroid (BA + CS), but not after bronchodilators only. Significant reductions with BA + CS were also found in BDR as a percentage of initial FEV1, and in BDR as a percentage of predicted FEV1. Bronchodilator tests were quite variable (SD 186 ml or 11% of initial value) and less than half of the patients could consistently be classified as "irreversible" with recommended cutoff levels. The bronchodilator response at the start of the study proved to be a poor predictor of improvement in FEV1 under BA + CS treatment (correct prediction 60%).. Bronchodilator responses decrease substantially with inhaled corticosteroid therapy, and within subject variability is considerable both in asthma and chronic obstructive pulmonary disease. Dichotomous decisions on whether patients are "irreversible" according to any single bronchodilator measurement should therefore be made with great caution. The bronchodilator response cannot be used accurately as a predictor of response to inhaled corticosteroids in obstructive airways disease.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Prognosis; Terbutaline

High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses.. Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic.. During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate.. This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Lung; Male; Middle Aged; Peak Expiratory Flow Rate

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Fluticasone; Humans; Lung; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Respiratory Function Tests

The safety of high dose inhaled steroids has been a subject of debate. The efficacy and safety of beclomethasone dipropionate and budesonide inhalations were evaluated by measuring their effects on pulmonary function, on the hypothalamic-pituitary-adrenocortical axis, and on carbohydrate metabolism in adults with unstable asthma.. Fifteen adults with unstable asthma and 15 healthy controls were studied. Eight patients were treated with beclomethasone dipropionate in initially high (2 mg/day for five months) and subsequently lower (1 mg/day for three months) doses. Seven patients were treated with budesonide at doses of 1.6 mg/day for five months followed by 0.8 mg/day for three months. Blood glucose and serum insulin were measured in an oral glucose tolerance test and plasma cortisol in an adrenocorticotrophic hormone test. The antiasthmatic effect of treatment was evaluated by measuring peak morning expiratory flow rates and forced expiratory volume in one second (FEV1).. The FEV1 increased significantly after one month of treatment (medians 88% v 96%, p < 0.01), and nocturnal symptoms disappeared within two weeks of treatment in both groups. At one month, the high dose significantly decreased serum insulin concentrations as calculated from the areas under the incremental two hours curves in the glucose tolerance test. The decrease was 59% for beclomethasone dipropionate (medians 76 v 31 mU/l/h, p < 0.005) and 42% for budesonide (medians 79 v 46 mU/l/h, p < 0.01). The median areas at five and eight months were intermediate for both drugs. No significant differences were found when the five and eight month values were compared either with the baseline or with one month values. The difference between the baseline values of both groups and the respective values in healthy controls was significant (medians 79 v 49 mU/l/h, p < 0.01). The one month values for the patients and control subjects were similar. Paralleling the changes for insulin, the area under the incremental two hour blood glucose curve decreased significantly (medians 1.4 v 0.4 mmol/l/h, p < 0.05) during the first month of treatment. The five and eight month values were intermediate (medians 0.8 and 0.7 mmol/l/h, respectively). These changes were not significant compared with the baseline or the one month areas. Similar changes were seen in both treatment groups. Neither treatment had any significant effect on plasma cortisol in the one hour adrenocorticotrophic hormone test.. In patients stressed by uncontrolled asthma, the antiasthmatic effect of high dose beclomethasone dipropionate and budesonide was accompanied by a significant initial decrease in insulin resistance with a parallel improvement in glucose tolerance. During prolonged treatment a small increase in insulin sensitivity was found. The overall effect of beclomethasone dipropionate and budesonide inhalations on carbohydrate metabolism may be beneficial in patients with uncontrolled asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Glucose; Bronchodilator Agents; Budesonide; Carbohydrates; Female; Glucocorticoids; Humans; Insulin; Male; Middle Aged; Pregnenediones

Five hundred and eighty-five patients with moderate asthma, currently receiving 400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks in a double-blind, randomized, parallel group study with either 500 micrograms day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500 micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000 micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all three treatment groups, mean morning and evening peak expiratory flow rates (PEFRs) increased within 1 week of the start of treatment. There were also improvements in clinic lung function, daytime and night-time asthma symptoms and a reduction in daytime and night-time rescue bronchodilator medication in all three groups. There were no statistically significant differences between the two formulations of fluticasone propionate in any of the efficacy parameters. Fluticasone propionate via the Diskhaler was significantly more effective than beclomethasone dipropionate over the 6 week study period in reducing diurnal variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03). Fluticasone propionate via the Diskhaler produced a statistically significant improvement in night-time symptoms when compared to beclomethasone dipropionate whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically significantly more effective than both formulations of fluticasone propionate in improving daytime symptoms (P < 0.05). However, these statistical differences must be viewed together with the fact that very few patients recorded a score of 2 or more for both daytime or night-time symptoms. There was a similarly low incidence of adverse events with all three treatments with no evidence of hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week comparative study showed that 500 micrograms day-1 fluticasone propionate whether administered via pressurized inhaler or Diskhaler is as effective and as safe as 1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized inhaler in the treatment of moderate asthma. Over 12 months fluticasone propionate 500 micrograms day-1 via a pressurized inhaler was at least as effective and as well tolerated as beclomethasone dipropionate 1000 micrograms day-1.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders

With mucosal inflammation contributing to the pathogenesis of asthma, it is increasingly accepted that long term steroid inhalers may induce remission in chronic long standing asthmatics. The present study involved 44 stable asthmatics who were randomly given either beclomethasone dipropionate inhaler (50 ug) 2 puffs qds or salbutamol inhaler (100 mcg) 2 puffs tds in addition to their oral bronchodilators. Pulmonary function testing, bronchoalveolar lavage and complete blood count were done at basal and weekly intervals and at the end of the study. The absolute eosinophil count showed a significant drop in the beclomethasone group as compared to the salbutamol group. Serial lung functions showed a significant improvement in the pre-bronchodilator PEFR and the pre-bronchodilator FVC in the beclomethasone group as compared to the salbutamol group. There was no significant change in the lavage eosinophil count pre and post-bronchodilator in both groups. Steroid inhalers are thus useful in long term management of bronchial asthma especially with respect to reducing bronchodilator requirement.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged

Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate, 400 micrograms, and 800 micrograms beclomethasone dipropionate from a dry powder inhaler. The design was a randomised, double blind, crossover trial. After a run in period of four days (period 1) the children were allocated to a sequence of active treatments in periods 2, 4, and 6. In periods 3 and 5 (wash out) placebo was given. All periods except the run in were two weeks long. The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week. Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34, 0.09, and 0.06 mm/week respectively. Compared with fluticasone propionate, treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Leg; Male; Risk Factors; Time Factors

To evaluate the clinical efficacy of high dose inhaled steroids, we examined the effects of standard doses (400 micrograms/day) and high doses (800 micrograms/day) of inhaled beclomethasone dipropionate (BDP, Becotide Inhaler), and the dose for regular use (800 micrograms/day) of salbutamol (Salb. Asmidon Air) on pulmonary function, bronchial hyperresponsiveness and asthma attack score. The subjects were 17 out-patients with mild or moderate bronchial asthma who were not receiving any anti-allergics or steroids. The patients were randomly allocated into three groups i.e., Group I: BDP 400 micrograms/day, Group II: BDP 800 micrograms/day and Group III: Salb. 800 micrograms/day. The administration period was 8 weeks. Pulmonary function test were performed and bronchial hyperresponsiveness was examined before and after the 8 weeks of treatment and attack scores were recorded during this period. It was found that inhalations of 400 micrograms/day and 800 micrograms/day BDP improved FEV1.0% value, peak flow, F-V curve, Dmin. and SGrs/Grs cont. Particularly, inhalation of 800 micrograms/day of BDP significantly improved these values and reduced attack scores in the early stages of the 8 week treatment. In contrast, there was a trend for inhalation of Salbutamol to enhance bronchial hyperresponsiveness and not to improve pulmonary function and asthma attack score. In conclusion, 800 micrograms/day of inhaled BDP is considered to be useful in the treatment of mild or moderate bronchial asthma.

Topics: Adult; Asthma; Beclomethasone; Female; Humans; Male; Middle Aged

In order to overcome the problem of poor co-ordination with the use of the conventional press and breathe metered dose inhaler, a breath-activated inhaler ('Autohaler' inhalation device) has been developed. The clinical response to equal doses of beclomethasone dipropionate administered from the 'Autohaler' device and the conventional metered dose inhaler was compared in 36 stable asthmatic patients receiving regular inhaled beclomethasone dipropionate. The study was performed using a double-blind, double-dummy crossover design. Each treatment was given for 4 weeks. Objective and subjective measures of asthma severity were compared in the second 14 days of each treatment period, with clinical equivalence defined as a difference of 20% or less in the adjusted mean values for the 30 patients with data from both treatment periods. Equivalence at the +/- 5% level was found in the objective measures of pre-bronchodilator FEV1 (p < or = 0.001); post-bronchodilator FEV1 (p < 0.001); morning and evening peak expiratory flow rate (both p < or = 0.001). Patient diary cards established there was equivalent usage of inhaled bronchodilator, and equivalent symptom scores for daytime disability and daytime and night-time breathlessness. The results show that, in stable asthmatics, treatment with beclomethasone dipropionate is clinically equivalent when delivered by the 'Autohaler' device or the conventional metered dose inhaler used efficiently.

Topics: Adult; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

The effects of high-dose inhaled budesonide (800 micrograms twice daily) and those of inhaled beclomethasone dipropionate (750 micrograms twice daily) were compared with respect to lung function, symptoms, bronchial reactivity and adrenocortical function in a doubleblind, double-dummy cross-over study. The subjects were 40 adult patients suffering from either allergic or non-allergic asthma. The asthma was categorized as moderate to severe, and the asthma was insufficiently controlled on inhalational steroids given in doses of 300 to 500 micrograms daily. After a two week "run-in" period the patients were randomized to six weeks treatment with either budesonide or beclomethasone dipropionate, followed by six weeks treatment with the opposite drug. Both inhaled budesonide and inhaled beclomethasone dipropionate were able to improve objective measures of lung function and bronchial sensitivity to histamine. Neither drug affected adrenocortical function, and no serious side-effects were noted during the trial. It is concluded that budesonide and beclomethasone dipropionate are safe and effective drugs for the treatment of asthma in adults. The substances are equally effective taken microgram for microgram.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex; Adult; Asthma; Beclomethasone; Bronchi; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Evaluation; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Pregnenediones

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg.ml-1, and forced expiratory volume in one second (FEV1) < 95% confidence intervals (CI) of predicted normal. The independent influences of baseline PC20FEV1, inspiratory vital capacity (IVC), bronchodilator response, smoking habits, and allergy both on the "immediate" (within 3 months) response in FEV1 and the change in long-term (from 3 months onwards) slope of FEV1 with inhaled corticosteroids were analysed. Patients had a larger "immediate" improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of "immediate" response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchi; Bronchial Hyperreactivity; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Male; Middle Aged; Prognosis; Smoking; Terbutaline

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

Nedocromil sodium is a non-steroidal prophylactic agent developed for the management of asthma. We have assessed the steroid sparing potential of inhaled nedocromil sodium 4 mg four times daily in a randomized, double blind, placebo controlled study in 69 asthmatic subjects controlled on inhaled beclomethasone dipropionate in the dose range 1000-2000 micrograms daily. Following a 4 week run-in period subjects added nedocromil sodium or placebo by metered dose inhaler to their usual medication for a further 4 weeks. The dose of inhaled steroid was then reduced at fortnightly intervals according to a predetermined schedule, with monitoring of asthma severity, symptom scores, bronchodilator use and peak flow recordings. Sixty subjects entered the steroid reduction phase and achieved median (range) % decreases in steroid dose of 80 (17-100)% with nedocromil sodium compared to 65 (0-100)% with placebo (P = 0.34) with 14 patients in the nedocromil sodium group and 10 in the placebo group being withdrawn completely from inhaled steroids. Subjective global assessment scores were significantly better with nedocromil sodium (mean 2.14) than with placebo (2.93; P < 0.02) though there was no difference between individual daily symptom scores. In this study therefore in asthmatic patients controlled on high doses of inhaled steroids, nedocromil sodium was well tolerated but the small differences in steroid sparing effect between nedocromil and placebo were not statistically significant.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nedocromil; Quinolones; Respiratory Function Tests

Twelve asthmatic patients received by inhalation for 2 weeks, in a double-blind, cross-over design, beclomethasone dipropionate (BDP; 600 micrograms/day) plus salbutamol (S; 900 micrograms/day), or S (900 micrograms/day) alone. Before and after each treatment course the subjects received intravenous cumulative doses of S up to 200 micrograms. In basal conditions and immediately before the next dose forced expiratory volume in 1 s (FEV1) and plasma cyclic AMP (cAMP) were measured. BDP+S treatment increased FEV1 basal values (p < 0.05) whereas inhaled S resulted in unsignificant improvement of ventilatory parameters. The slopes of the dose-response curves of FEV1 and plasma cAMP to intravenous S were unaffected by the two treatment courses. Our results suggest that DBP+S, differently from S alone, improves ventilatory function in asthmatic patients and that neither S nor S+BDP seem to affect adrenergic function.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Cyclic AMP; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged

We investigated the effect of 5 months of treatment with inhaled beclomethasone dipropionate (BDP) on the airway responsiveness to methacholine (PD20 FEV1) and to toluene diisocyanate (TDI) in 15 sensitized asthmatic subjects who had been removed from occupational exposure to TDI. After the diagnosis was established by a positive inhalation challenge with TDI, each subject was removed from occupational exposure to isocyanates and treated with either BDP (1 mg twice per day, n = 7) or placebo (n = 8) for 5 months. The study was double blind for parallel groups. P20 FEV1 methacholine was measured before and three times during treatment and then at 6 months, that is, 4 wk after cessation of treatment. Airway sensitivity to TDI was assessed with specific inhalation challenge before treatment and at 6 months. Beclomethasone reduced the airway hyperresponsiveness to methacholine but did not affect the response to TDI. In fact, in the subjects on BDP, P20 FEV1 increased from 0.145 to 0.485 mg (p < 0.05) after 2 months of treatment. A further increase was observed at 4 and 5 months (0.548 and 0.629 mg, respectively, p < 0.01), and the improvement in nonspecific airway responsiveness was maintained after a 1-month washout period (0.637 mg, p < 0.01). In contrast, in the subjects on placebo, P20 FEV1 did not change significantly. At the end of the study, the severity of asthmatic reactions induced by bronchial challenge with TDI was significantly reduced in both groups, but no differences were observed between placebo and BDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Hypoglycemia; Insulin; Male; Methacholine Chloride; Middle Aged; Occupational Diseases; Placebos; Toluene 2,4-Diisocyanate

Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Placebos; Respiration; Single-Blind Method; Tidal Volume; Time Factors; Vital Capacity

The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.

Topics: Administration, Intranasal; Adolescent; Analysis of Variance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Circadian Rhythm; Double-Blind Method; Humans; Methacholine Chloride; Rhinitis, Allergic, Seasonal; Time Factors

We investigated the effect of 300 micrograms of inhaled beclomethasone dipropionate (BDP) daily on bronchial responsiveness to methacholine and pulmonary function of 22 subjects with asthma in a single-blind, crossover study. The severity of bronchial hyperresponsiveness lessened significantly during treatment with BDP (P < .01). No significant changes occurred in FEV1 or in the control value of airway conductance. We conclude that a 300-micrograms total daily dose of BDP is an efficacious treatment for patients with asthma. Because suppression of adrenal function and systemic adverse effects can occur in asthmatic patients treated with inhaled corticosteroids, especially children, long-term treatment with inhaled steroids should employ minimal daily doses necessary.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Beclomethasone; Bronchi; Child; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Single-Blind Method; Theophylline

To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid.. A 4-year prospective study.. Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands.. The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study.. During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 micrograms, or ipratropium bromide, 40 micrograms). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 micrograms two times daily.. Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyperresponsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups.. Adding beclomethasone, 800 micrograms daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchodilator Agents; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Respiratory Function Tests; Smoking; Treatment Outcome

In a double-blind, placebo-controlled study control of asthma was assessed by diary symptom cards, peak-flow measurements and lung function within 3 treatment groups over a 6 months period. 36 children (25 boys, 11 girls 5.5 to 13.2 years of age) with exogen allergic, perennial asthma inhaled either beclomethasone dipropionate (BDP) with salbutamol (S) or disodium cromoglycate (DNCG) with S or a placebo preparation with S from metered dose inhalers (MDI) through a large-spaced auxiliary device (Volumatic). At entry, after 2 and 4 months lung function tests were performed evaluating changes in the degree of pulmonary hyperinflation, bronchial obstruction, and bronchial hyperreactivity (BHR). Daily PF measurements showing wide variations (up to 10-12%) were insensitive to indicate any significant changes. In contrast evaluation of symptom diaries presented dramatic improvement during the first 3 months of the study. In addition, the DNCG group showed significant improvement of BHR (p = 0.02). Moreover, the majority of patients on regular therapy with salbutamol and placebo showed an increase of airway resistance. It is concluded that even in mild childhood asthma, for optimal control a combination of a beta 2-stimulant as bronchodilator and DNCG or BDP as protector should be applied.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Child; Cromolyn Sodium; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male

The systemic effects of the inhaled corticosteroid beclomethasone dipropionate are reduced if the drug is inhaled through a large volume spacer. Use of spacers may therefore permit higher doses to be given without causing hypothalamo-pituitary-adrenal suppression.. Randomised, double blind, double dummy, parallel group study was carried out in adults with chronic asthma to determine the dose of beclomethasone dipropionate causing hypothalamo-pituitary-adrenal suppression when the drug was administered by metered dose aerosol with and without a large volume spacer. After a four week run in taking 1.5 mg beclomethasone daily 50 patients underwent tests of hypothalamo-pituitary-adrenal function (measurement of 0900 h serum cortisol concentration and 24 hour urinary free cortisol excretion and the short tetracosactrin test). Six patients had hypothalamo-pituitary-adrenal suppression (results of at least two tests subnormal) and asthma was well controlled in six others. Thirty eight patients received increasing doses of beclomethasone with (group S) or without (group MDI) a 750 ml spacer. The daily dose was increased by 0.5 mg at monthly intervals until hypothalamo-pituitary-adrenal suppression developed or a dose of 5 mg/day was achieved. Asthma symptoms and peak expiratory flow were recorded daily.. Twenty three patients completed the study, one (group S) reaching a dose of 5 mg beclomethasone dipropionate daily without hypothalamo-pituitary-adrenal suppression. Reasons for withdrawal were poor compliance (n = 10), the patient's decision (n = 3), and asthma that was too unstable (n = 2). "Intention to treat" analysis showed that the median dose of beclomethasone causing hypothalamo-pituitary-adrenal suppression was similar in the two groups (3.25 mg in S v 3.0 mg in MDI; 95% confidence interval (CI) for difference -1.0 to 1.0 mg). At 2 mg/day of beclomethasone most patients in both groups had well controlled asthma and there were no differences in symptoms or peak flow between the groups. Good control at this dose did not permit conclusions to be drawn about the efficacy of higher doses.. There is wide interindividual variation in the dose of beclomethasone dipropionate causing hypothalamo-pituitary-adrenal suppression. Whether or not a spacer is used, doses higher than the currently accepted maximum of 2 mg/day can be taken by many adults with asthma without causing subnormal function of the hypothalamo-pituitary-adrenal axis. Whether these higher doses are more effective in controlling asthma remains to be established.

Topics: Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System; Prednisolone

The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Biopsy; Bronchi; Bronchoscopy; Carbachol; Double-Blind Method; Epithelium; Female; Forced Expiratory Volume; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Male

Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn.. In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20.. The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18).. Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Bronchial Provocation Tests; Cromolyn Sodium; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride

To compare the benefits and adverse reactions of theophylline and beclomethasone (BDP) in the long-term control of mild to moderate chronic asthma in children.. Multicentered, double-blind, double-placebo, randomized, controlled trial.. One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma.. Treatment with either BDP, 84 micrograms four times a day, or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms.. Daily diary record of symptoms, peak flow rates, supplemental bronchodilator and glucocorticoid treatment, doctor and hospital visits, absence from work and school, and side effects.. Aerosol BDP and sustained-release theophylline were effective primary treatments for mild to moderate chronic asthma. Beclomethasone resulted in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline. Side effects were observed significantly more frequently with theophylline than with BDP. Growth velocity suppression was noted with BDP and was more pronounced in boys. Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation.. Both theophylline and BDP are effective therapy for mild to moderate asthma. Caution must be used with the administration of BDP in children because of possible growth velocity suppression.

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Child; Chronic Disease; Double-Blind Method; Female; Forced Expiratory Volume; Growth; Humans; Male; Peak Expiratory Flow Rate; Theophylline; Treatment Outcome

165 patients (106 males, 59 females) entered an open group comparative study of a 12-week test treatment on bronchial hyperresponsiveness (BHR) determined by methacholine challenge. Patients were randomly allocated to receive nedocromil sodium (4 mg q.i.d.), sodium cromoglycate (10 micrograms q.i.d.) and beclomethasone dipropionate (500 micrograms t.i.d.). At the end of the study, an 2.25-fold increase of the PD20FEV1 was noted in all the treated patients. No significant difference was noted among the treatments.

Topics: Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Cromolyn Sodium; Female; Humans; Long-Term Care; Male; Middle Aged; Nedocromil; Quinolones

In a randomized, cross-over study we compared the effects of inhaled nedocromil sodium, 4 mg q.i.d., with inhaled beclomethasone dipropionate, 200 micrograms q.i.d. in 23 atopic asthmatic patients. After a 3 week single-blind placebo period, regarded as the baseline, and after 4 and 8 weeks of active treatment, drug effects were assessed with regard to bronchial hyperresponsiveness to histamine and distilled water, lung function and beta 2-agonist use. After 4 and 8 weeks of treatment, nedocromil sodium reduced the histamine responsiveness (p < 0.005 and p < 0.0005), but not the distilled water responsiveness, and did not improve lung function and peakflow measurements compared to baseline. After 4 and 8 weeks of treatment, beclomethasone caused a significant increase in lung function (p < 0.005) and decrease in bronchial hyperresponsiveness to histamine (p < 0.0005) and distilled water (p < 0.0005) as compared to baseline. beta 2-agonist use was significantly diminished after an 8 week treatment with beclomethasone, whereas nedocromil sodium had no effect. Treatment with beclomethasone was superior to treatment with nedocromil sodium with regard to bronchial hyperresponsiveness to histamine and distilled water (p < 0.0005 and p < 0.005), lung function (p = 0.003), peakflow measurements (p < 0.05) and beta 2-agonist use (p < 0.005).

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Histamine; Humans; Male; Middle Aged; Nedocromil; Quinolones; Single-Blind Method; Water

With the aim of devising an improved beta 2-agonist treatment regimen for patients presenting with acute severe resistant asthma, a double-blind, placebo-controlled randomised study of the effect of fenoterol and beclomethasone inhalations was done in 40 patients. Fenoterol inhalations had minimal effect in acute resistant asthma, but significant improvement was obtained when beclomethasone inhalations were given before fenoterol inhalations. Sequential beclomethasone and fenoterol inhalations can therefore be used as a preliminary emergency treatment for these patients.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Asthma; Beclomethasone; Double-Blind Method; Drug Resistance; Fenoterol; Humans; Respiratory Function Tests

We studied 16 asthmatic subjects sensitive to changes in airway osmolarity to determine whether nedocromil sodium has any effect on airway narrowing caused by hypertonic saline challenges. Nedocromil sodium (10 mg) or its vehicle was inhaled 10 min before a challenge with ultrasonically nebulized 4.5% NaCl. FEV1 was measured before challenge and 1 min after each challenge period of 0.5, 1, 2, 4, 8, 8 and 8 min. The challenge was stopped when there was a 20% fall in FEV1 from baseline or after the final challenge period. We measured airway sensitivity, that is, the provoking dose of 4.5% NaCl required to induce a 20% reduction in FEV1 (PD20FEV1) and calculated the fold difference in PD20FEV1 after the intervention. After inhaling nedocromil sodium there was a 3.95-fold improvement in PD20 (p < 0.001) when compared with the vehicle day. After pretreatment with nedocromil sodium two of the 16 subjects were completely protected against 4.5% NaCl challenge, and six developed a plateau in their response. We conclude that nedocromil sodium is effective in reducing airway narrowing in response to 4.5% NaCl challenge in asthmatic subjects, and it appears to be unique in its ability to produce a plateau in response to acute administration of a drug before a bronchial challenge.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Body Height; Bronchial Provocation Tests; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nedocromil; Quinolones; Saline Solution, Hypertonic; Sensitivity and Specificity

The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchoconstriction; Bronchodilator Agents; Drug Evaluation; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Treatment Outcome

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Topics: Adult; Airway Resistance; Asthma; Beclomethasone; Blood Cell Count; Blood Proteins; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Confounding Factors, Epidemiologic; Eosinophil Granule Proteins; Eosinophils; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Histamine; Humans; Hypersensitivity; Lymphocyte Activation; Male; Receptors, Interleukin-2; Ribonucleases; Sputum

Undertreatment of chronic asthma may reflect uncertainty as to how it may be best controlled. We compared the effects of increased inhaled corticosteroid vs regular inhaled bronchodilator in 32 adult asthmatics. During three 16-week treatment periods, comprising baseline inhaled corticosteroid (mean 505 micrograms daily) and on-demand beta-agonist, baseline inhaled corticosteroid and increased (regularly scheduled four times daily) beta-agonist, and increased inhaled corticosteroid (mean 1478 micrograms daily) and on-demand beta-agonist, subjects recorded symptoms, morning and evening peak flow, and additional medication. Of 25 subjects whose control differed significantly between treatments with baseline vs increased corticosteroid, 22 (88 percent) favored the increased dosage (p < 0.001). Of 28 subjects whose control differed between treatments with regular beta-agonist vs increased corticosteroid, 24 (86 percent) were better controlled with increased inhaled corticosteroid and were worse with regular beta-agonist (p < 0.001). Only one quarter the number of exacerbations were experienced during treatment with increased inhaled corticosteroid. Upper airway adverse effects were minor and easily controlled. Hence, asthma with persistent symptoms was better controlled by increased inhaled corticosteroid therapy than by increased use of inhaled beta-agonist.

Topics: Administration, Inhalation; Adult; Aerosols; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Circadian Rhythm; Double-Blind Method; Drug Administration Schedule; Fenoterol; Humans; Peak Expiratory Flow Rate; Prednisone; Pregnenediones; Terbutaline

Two different beclomethasone dipropionate inhalation aerosols (Andion and Becotide) were compared in a double-blind, cross-over study in patients with stable, steroid-dependent asthma. Fifty-two patients were included in the study, and 44 completed the two 6-week periods of treatment. The difference in therapeutic efficacy on FEV1 between Andion and Becotide was -0.018 1, and likewise no differences in therapeutic efficacy on FVC and peak expiratory flow were found. There were no significant differences between the two treatment periods regarding peak expiratory flow rates, symptoms, frequency of adverse effects, and amount of salbutamol and beclomethasone dipropionate employed. In conclusion, no significant differences could be demonstrated between Andion and Becotide with regard to pulmonary function, symptoms, and frequency of adverse effects in the treatment of patients with steroid-dependent bronchial asthma.

Topics: Adult; Aged; Asthma; Beclomethasone; Double-Blind Method; Drug Evaluation; Drugs, Generic; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Therapeutic Equivalency

We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyperresponsiveness (PD20 methacholine < 8 mumol or a > 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P < 0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P = 0.03).

Topics: Administration, Intranasal; Adult; Asthma; Beclomethasone; Bronchial Provocation Tests; Double-Blind Method; Humans; Immunoglobulin E; Middle Aged; Respiratory Sounds; Rhinitis, Allergic, Seasonal

The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma.

Topics: Administration, Inhalation; Adolescent; Airway Resistance; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Child, Preschool; Exercise Test; Forced Expiratory Volume; Humans; Time Factors

Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.

Topics: Administration, Intranasal; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Double-Blind Method; Forced Expiratory Volume; Humans; Medical Records; Peak Expiratory Flow Rate; Pollen; Rhinitis, Allergic, Seasonal; Seasons

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Statistical; Pregnenediones; Respiratory Mechanics

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.

Topics: Adult; Asthma; Beclomethasone; Bronchial Hyperreactivity; Double-Blind Method; Follow-Up Studies; Forced Expiratory Volume; Humans; Ipratropium; Lung Diseases, Obstructive; Middle Aged; Multicenter Studies as Topic; Pilot Projects; Regression Analysis; Terbutaline; Time Factors; Total Lung Capacity

Three combination regimens, (1) inhaled albuterol (ALB) with oral theophylline (THEO), (2) inhaled ALB with inhaled beclomethasone dipropionate (BDP), or (3) inhaled ALB, inhaled BDP, and oral THEO, were evaluated and compared as optimal pharmacotherapy for chronic asthma in 111 children. In this double-blind, parallel-group, multicenter study, children, aged 6 to 16 years with moderately severe asthma (unstable despite daily medications), were treated with one of the combinations for 12 weeks. Patients were evaluated every 4 weeks by spirometry and serum THEO measurement. Patients kept daily symptom diaries, measured peak flow rates twice daily, and recorded adverse events. Treatment groups did not differ in disease or demographic characteristics at study entry. All three combination treatments provided and maintained significant improvement in FVC, FEV1, and FEF25%-75% volume points, and compared with that of pretreatment, with no significant differences between treatments. Throughout the 12-week treatment period, however, patients receiving BDP had lower symptom scores, fewer had more than one asthma attack, fewer required "bursts" of prednisone (p = 0.001), and fewer required rescue medication (p = 0.009). Significantly more patients receiving BDP said that they felt better than they did at the beginning of the study compared with the number of patients not receiving BDP (p = 0.002). Adverse events were similar among treatment groups.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Albuterol; Asthma; Beclomethasone; Chi-Square Distribution; Child; Chronic Disease; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Humans; Theophylline

We investigated whether regular use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate (BDP) inhalation is necessary in chronic bronchial asthma. Twenty chronic asthmatic patients who were stable on regular BDP and beta-agonist inhalation were studied. After a 2 week observation period, the patients were randomly assigned to two groups. One group received BDP 400 micrograms/day (2 puffs 4 times) and beta-agonist inhalation as required for 4 weeks. This period was followed by 4 weeks of treatment with BDP 400 micrograms/day and regular beta-agonist inhalation. The other group received these treatments in the reverse order. No significant differences among the two groups were observed in attack score, ADL score, sleep score, and %PEFR. In addition, no differences were detected in these parameters between the periods of regular use of beta-agonist and the periods of use as required. The frequency of inhalation of beta-agonist during the use as required period correlated with the sleep score and difference in %PEFR between morning and night, and was significantly lower than the frequency of inhalation during the period of regular. From these results, we conclude that inhalation of beta-agonist on a regular basis is not necessary to achieve the same degree of relief of symptoms as treatment with beta 2-agonist and BDP inhalation on regular basis in patients with chronic asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.

Topics: Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nedocromil; Peak Expiratory Flow Rate; Quinolones; Vital Capacity

Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Ethanolamines; Follow-Up Studies; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Efficacy and safety of salbutamol--beclomethasone combination were studied in a multicentre trial in general practice which included 1917 asthmatic patients. During a 7 day run-in period, the number of dyspnea episodes, the morning and evening PEFR values were recorded daily. Patients were then treated with 2 puffs of salbutamol--beclomethasone combination t.i.d. or q.i.d. Results showed a significant improvement of the daily number dyspnea episodes (from 2.7 to 1.4) and of the daily number of salbutamol puffs used as rescue medication (from 5,1 to 2,5) (p less than 0.001). Morning and evening PEFR were increased by 50 litres min-1 (p less than 0.001). Symptoms were significantly improved, particularly nocturnal dyspnea (p less than 0.001). Minor and usual adverse events were noted in only 2,7% of the population. Salbutamol--beclomethasone allows a good control of asthma, particularly a good nocturnal cover. This efficacy with a good safety profile makes salbutamol--beclomethasone combination a well-adapted maintenance treatment of asthma.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Albuterol; Asthma; Beclomethasone; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged

The effect of a week treatment with inhaled salbutamol plus placebo (S+P) vs. salbutamol combined with beclomethasone dipropionate (S+BDP) on early and late asthmatic responses to inhaled allergen was studied in ten atopic patients in a randomized, double-blind, cross-over study. All patients had previously shown a dual type response to the specific bronchial provocative test (sBPT). Each patient performed two periods of treatment for a week, with a 15 day interval between them: (a) salbutamol 0.3 mg, tid + placebo; (b) salbutamol 0.3 mg+BDP 0.2 mg, tid; at the end of each treatment period, sBPT was performed and the last treatments were given 1.5-2 h before and 3-4 h after allergen challenge. S + BDP completely prevented both early and late responses to allergen, while S + P reduced but did not completely inhibit early and late responses. The difference between the two treatments was significant for early and late asthmatic responses. Non-specific bronchial hyperresponsiveness to methacholine was performed before each treatment period, after 6 days of treatment before sBPT and the day after sBPT at the end of the treatment period; there was only a mild increase in PD15FEV1 methacholine after 6 days of treatment with S + BDP in comparison with S + P treatment. These results suggest that salbutamol plus beclomethasone may be used effectively in the prophylaxis of early and late asthmatic reactions induced by allergen in sensitized subjects.

Topics: Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Bronchial Provocation Tests; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Time Factors

In order to investigate the efficacy of steroid inhalation in treating asthma of moderate severity, a single-blind, randomized short-term (3-4 weeks) trial was performed in 25 asthmatics uncontrolled by salbutamol inhalation, oral aminophylline and beta 2-agonist. 22 patients finished the trial. Among them, twelve received beclomethasone dipropionate 300 mcg/day and ten received placebo. There was significant improvement in asthmatic symptoms and pulmonary function (FEV1.0, V50, V25) in the group treated with steroid inhalation at the end of this trial, whereas no significant changes were observed in the placebo group. The results demonstrated that steroid inhalation could effectively control asthma of moderate severity.

Topics: Administration, Inhalation; Adult; Aerosols; Asthma; Beclomethasone; Female; Humans; Male; Respiratory Function Tests; Single-Blind Method

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisone; Vital Capacity

In this double blind study we evaluated the effect of a 2 months long treatment with inhaled beclomethasone dipropionate (300 micrograms/day) on methacholine responses in asthmatic children, during a period of maximal allergen exposure. Baseline values of methacholine PC20-FEV1 were 0.66 +/- 0.22 mg/mL (mean +/- SEM) in 10 children treated with the active drug and 0.78 +/- 0.21 mg/mL in 10 children treated with placebo. After 1 month of treatment PC20-FEV1 was 1.91 +/- 0.64 and 0.80 +/- 0.33 mg/mL, respectively, in the groups treated with beclomethasone versus placebo. A statistically significant reduction in bronchial hyperreactivity (PC20-FEV1, 5.49 +/- 1.86 mg/mL) but no systemic side effects were observed after 2 months of treatment with beclomethasone dipropionate. This is compared with a PC20-FEV1 of 1.38 +/- 0.52 mg/mL in the placebo group. The results confirm the effect of inhaled corticosteroids in reducing bronchial hyperreactivity, even during a period of maximal allergen exposure.

Topics: Allergens; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Child; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Nebulizers and Vaporizers

Budesonide 400 micrograms daily, in nonsteroid-dependent asthma, can produce improvements in airway responsiveness and clinical asthma severity, with some patients returning to normal responsiveness and becoming asymptomatic. This study examined whether similar improvements occur when asthmatics, who are dependent upon inhaled steroids, take either a regular maintenance dose of inhaled steroid or twice that amount for a year. Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome. In a double-blind, randomized manner, half were assigned to remain on a maintenance dose (MD) and the rest received twice that dose (MDx2) for one year. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, inhaled bronchodilator use and number of asthma exacerbations. There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups. Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance. This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Evaluation; Female; Forced Expiratory Volume; Humans; Lung; Male; Methacholine Chloride; Middle Aged; Pregnenediones; Substance-Related Disorders; Time Factors

The aim of the present study was to investigate the effects of a three months' treatment with beclomethasone dipropionate on the bronchial mucosa of asthmatic patients. Eleven patients suffering from a mild chronic asthma treated with inhaled salbutamol and theophylline were randomly assigned to receive either 1000 mu g of beclomethasone dipropionate (6 patients) or an aerosolized placebo (5 patients) in a double-blind manner. Bronchial biopsies and bronchial secretions were obtained through a fiberoptic procedure at the beginning and the end of the study. Repeated clinical and spirometric investigations were performed each month. Inter- and intra-group mean changes of clinical symptoms and of spirometric values were not significantly different. Pathogens were rarely found in bronchial aspirates and their occurrence did not seem to be influenced by the beclomethasone therapy. Sixty percent of the bronchial biopsies displayed pathological changes of the mucosa that observed at the beginning and at the end of the study; however, no sign of mucosal atrophy was noted.

Topics: Adult; Asthma; Beclomethasone; Bronchi; Bronchoalveolar Lavage Fluid; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Placebos; Prospective Studies; Spirometry

We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was less than 8 mg/ml, the postbronchodilator FEV1 was greater than 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 micrograms beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p less than 0.001). FEV1 did not change after treatment with placebo or nedocromil (p greater than 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p less than 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p less than 0.01), but not after nedocromil or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Methacholine Compounds; Middle Aged; Nedocromil; Quinolones; Skin Tests

Two hundred and two patients aged 12-78 with chiefly moderate to severe asthma took part in a multicenter randomized blinded group comparison of nedocromil sodium (NS) 4 mg four times daily, beclomethasone dipropionate (BD) 0.1 mg four times daily, and placebo. Patients were assessed at the start and end of a two week baseline and after three and six weeks of treatment. Compared with placebo, both NS and BD significantly improved daytime dyspnoea and day and nighttime cough, as assessed by diary card scores. Lung function (FEV1) was significantly improved in the BD group. In the NS group there was also a significant reduction in concomitant use of inhaled beta 2-agonists. Overall opinions of efficacy by clinicians and patients were significantly in favor of both active treatments over placebo. There were no significant differences between the three treatments for peak expiratory flow rates, morning tightness or nighttime dyspnoea. Comparison between the two active treatments showed no significant differences in any of the variables.

Topics: Adolescent; Adult; Aged; Airway Resistance; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Nedocromil; Peak Expiratory Flow Rate; Quinolones; Randomized Controlled Trials as Topic; Single-Blind Method

We have compared the effects of inhaled beclomethasone dipropionate (BDP) 400 micrograms day-1 with inhaled nedocromil sodium (NDS) 16 mg day-1 as additional therapy in adults with asthma not fully controlled by regular beta-2-agonist inhalers with, or without, oral theophyllines. Seventeen subjects were entered into a 2-week baseline phase, and subsequently in a double-blind crossover fashion into two 8-week phases of daily BDP or NDS. Subjects recorded daily peak expiratory flow rates, morning and evening (PEF am and pm), symptom scores and beta-2-agonist inhaler use. Thirteen subjects completed the study and the last 2 weeks of each phase were analysed. Compared to baseline, both BDP and NDS caused a significant improvement in PEF am (P less than 0.05), PEF pm (P less than 0.05) and the 'amplitude % mean' (P less than 0.001). Both drugs gave a highly significant improvement in all symptom scores. There was no significant difference between BDP and NDS for PEF am, PEF pm, amplitude % mean, cough and daytime asthma score. However, beta-2-agonist inhaler use and scores for nocturnal asthma and morning tightness were all significantly better in the BDP phase, and may have contributed to its better overall subjective performance. Thus, both NDS and BDP resulted in a significant improvement in asthma control in the subjects studied, and both drugs caused a similar improvement in PEF.

Topics: Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nedocromil; Peak Expiratory Flow Rate; Quinolones; Time Factors

In a double blind, controlled trial, the effect of high dose beclomethasone dipropionate (750 micrograms three times daily for five days) administered by metered dose inhaler and valved spacer, was compared with placebo, during 70 paired episodes of acute asthma in 24 preschool children. Treatment commenced at home at the first sign of an attack. Parents' blind preference for active treatment was significant. Data from 17 pairs of treatment, however, were affected by interventions such as hospital admission or oral corticosteroid treatment. These events occurred similarly in active and control periods. An intrasubject comparison was made of diary scores from the 18 pairs of episodes in which no intervention occurred in either the active or placebo treatment. Both daytime and night symptoms over the first week of the attack were significantly reduced by active treatment. Intermittent high dose inhaled beclomethasone dipropionate is beneficial in modifying the severity of acute episodic asthma in preschool children able to use a spacer device.

Topics: Acute Disease; Administration, Inhalation; Asthma; Beclomethasone; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Home Nursing; Humans; Infant

The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.

Topics: Adult; Airway Resistance; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Histamine; Humans; Lung; Male; Middle Aged; Random Allocation

In a double-blind cross-over study of 12 asthmatic patients the effects of 1,000 micrograms.day-1 beclomethasone dipropionate (BDP) on airway function, bronchial reactivity and hypothalamic-pituitary-adrenal (HPA) axis have been compared to those of 15 mg.day-1 oral prednisone (PRD). None of the patients had ever received corticosteroids before. Fourteen days treatment with either of both steroids improved airway function, both subjectively and objectively. Both steroids slightly reduced the responsiveness to histamine. PRD suppressed the corticotrophin-releasing factor (CRF) stimulated cortisol release more than BDP did, whereas there was no significant change in adrenocorticotrophic hormone (ACTH) release. The results indicate that short-term treatment with 1,000 micrograms.day-1 BDP reduces bronchial hyperreactivity (BHR) in asthmatic patients, whilst having subtle effects on HPA axis.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Prednisone

To investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli, we studied 25 subjects with mild asthma with a double-blind, noncrossover design to compare the effect of a 3-week treatment with salbutamol (0.2 mg, four times a day [q.i.d.]) and placebo (N = 11) to the effect of salbutamol (0.2 mg q.i.d.) and inhaled beclomethasone dipropionate (BDP, 0.5 mg q.i.d.) (N = 14). Airway response to histamine and methacholine was assessed as the provocative concentration (in milligrams per milliliter) necessary to increase the specific airway resistance (SRaw) (in centimeters of H2O times second) by 100% (PC100 SRaw). Airway response to hyperventilation of air and to hyperventilation of 0.75 ppm of sulfur dioxide (SO2) was determined as the provocative ventilation (in liters per minute) necessary to increase SRaw by 75% (PV75 SRaw). Challenges were performed on separate days before and after treatment, and salbutamol inhalation was withheld at least 6 hours before each challenge. Salbutamol and placebo did not change perchallenge baseline SRaw nor did they have any significant effect on the airway response to the stimuli. Salbutamol and BDP decreased the mean prechallenge baseline SRaw (SEM) from 7.7 (0.37) to 5.9 (0.28) (p less than 0.01) and significantly (p less than 0.01) increased geometric mean (SEM) PC100 SRaw for histamine from 0.5 (1.42) to 0.9 (1.53) mg/ml; for methacholine, from 0.2 (1.47) to 0.5 (1.51) mg/ml; and mean (SEM) PV75 SRaw for hyperventilation of air from 51.8 (2.32) to 58.4 (1.86) L/min. In contrast, the change of PV75 SRaw during hyperventilation of SO2 from 26.2 (2.29) to 31.4 (3.30) L/min was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Airway Resistance; Albuterol; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Histamine; Humans; Hyperventilation; Methacholine Chloride; Sulfur Dioxide

A community based, prospective study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken. One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol. Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a 'partially double-blind' manner. The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1. All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority. Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone, particularly when inhaled steroids were started in relatively high dosage.

Topics: Administration, Inhalation; Adult; Albuterol; Asthma; Beclomethasone; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Prospective Studies

The effect of four weeks of treatment with beclomethasone dipropionate (BDP, 500 micrograms twice daily) on the bronchial responsiveness to propranolol was examined in 16 patients with mild asthma in a placebo-controlled, double-blind crossover study. Propranolol was inhaled in doubling concentrations and the results were expressed as the cumulative dose producing a 20 percent fall in FEV1 (PC20). After four weeks of treatment with BDP, the mean FEV1 increased from 82.0 percent predicted to 88.1 percent predicted. The difference was significant (p less than 0.001). Treatment with BDP did not significantly change the responsiveness to propranolol, the geometric mean PC20 being 3.17 mg/ml before and 3.64 mg/ml after BDP treatment. The recovery of FEV1 was faster after 60 minutes of BDP treatment in comparison with placebo treatment (beyond 90 minutes). This study suggests that BDP treatment is unable to reduce bronchial responsiveness to propranolol but can accelerate the recovery of bronchoconstriction induced by propranolol in asthmatic patients.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchial Spasm; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Propranolol; Random Allocation; Time Factors

Two therapeutic trials aimed at determining whether a high-dose inhaled corticosteroid, beclomethasone dipropionate (BDP), could reduce or suppress a long term and continuous treatment with a systemic corticosteroid, triamcinolone acetonide (TA), were carried out in a homogeneous population of severe, steroid-dependent asthmatics. The first one was a controlled, double-blind versus placebo trial involving 25 patients followed up for 5 months. The second one was an open trial involving 105 patients followed up for 12 months. In both trials the mean doses of TA were reduced by 60 to 65 per cent, and TA could be totally or nearly totally suppressed in almost 60 per cent of the cases with clinical and functional results that were equal or superior to those previously obtained with systemic corticosteroid therapy. It is concluded that: (a) continuous systemic corticosteroid therapy in mean doses of more than 5 mg/day of prednisone equivalent is now rarely indicated in patients with steroid-dependent asthma, and (b) inhaled corticosteroid therapy with BDP could be extended to cases of non steroid-dependent asthma inadequately controlled by bronchodilators.

Topics: Administration, Inhalation; Adult; Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Male; Middle Aged; Respiratory Function Tests; Triamcinolone Acetonide

The efficacy of nedocromil sodium (NED) (4 mg twice daily) and beclomethasone dipropionate (BDP) (200 micrograms twice daily) in controlling the symptoms of asthma, the pulmonary function, and bronchial responsiveness to histamine was assessed in a double-blind, double-dummy, crossover study of 39 adult patients with chronic asthma. The patients, most of whom were assessed to be affected to a moderate degree, were insufficiently controlled in their current regimen of inhaled and/or oral bronchodilators. A 2-week baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups demonstrated improvements from baseline in clinical assessment of lung function performed after the first 6 weeks of treatment. No significant differences were observed when the effects of the treatments were compared on FEV1, FVC, and peak expiratory flow. Bronchial reactivity to histamine, measured as the amount of histamine causing a 20% fall in FEV1 (PC20), decreased significantly (p less than 0.05) after 6 weeks of treatment with BDP compared to the effect of NED treatment. Asthma severity, symptom score, and inhaled bronchodilator use demonstrated significantly better results with BDP. After crossover of treatment, the group transferring from NED to BDP continued to improve, whereas the group crossing from BDP to NED tended to demonstrate a major deterioration during the first 3 weeks, after which a stabilization or an increase in FEV1, FVC, and ln PC20 appeared to occur. It is concluded that NED for inhalation is a potent new drug for treatment of both atopic and nonatopic subjects with asthma. With the number of patients and dosages used, the effect on the pulmonary function was not significantly different from that of BDP after the initial 6 weeks of treatment, but BDP had a better effect on asthma severity, overall opinions, symptom score, bronchodilator use, ln PC20, and morning peak expiratory flow.

Topics: Adult; Aerosols; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Double-Blind Method; Drug Evaluation; Female; Humans; Lung; Male; Nedocromil; Quinolones; Random Allocation; Respiratory Function Tests

A multi-centre, randomized, blind comparative group study was carried out in 202 adult patients, who had suffered from asthma for at least 2 years, to assess the effectiveness and tolerability of maintenance treatment with either 4 mg nedocromil sodium 4-times daily, 0.1 mg beclomethasone dipropionate 4-times daily or 2 puffs of placebo 4-times daily, given by inhalation. Lung function (FEV1 and sRaw) measurements were made at the beginning and end of a 2-week baseline period and then after 3 and 6 weeks of treatment: assessment were also made of asthma severity. Patients recorded daily on diary cards details of morning and evening PEFR, usage of inhaled bronchodilators, severity of dyspnoea, cough and morning tightness. The results showed that, compared with placebo, both nedocromil sodium and beclomethasone dipropionate-treated patients showed an improvement in FEV1 and a reduction in sRaw values: PEFR increased slightly in all three groups. There was an improvement in asthma severity, diminished rate of dyspnoea and cough, and reduced usage of inhaled bronchodilators in patients receiving active treatment but not in those on placebo. Overall assessment of treatment efficacy by both investigators and patients showed that opinions were significantly in favour of active treatment over placebo. Treatment was well tolerated and no serious side-effects were reported. It was concluded that at the dosages used nedocromil sodium was comparable with and equivalent to inhaled beclomethasone dipropionate in nearly all of the parameters assessed, and both drugs were superior to placebo in the maintenance treatment of asthma in adult patients.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Asthma; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Nedocromil; Placebos; Quinolones; Randomized Controlled Trials as Topic

In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.

Topics: Administration, Inhalation; Adult; Aged; Asthma; Beclomethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prednisolone; Random Allocation

The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Pregnenediones

Hormonal inhalation preparations (Becotide, Beclomet) were given to 59 children aged 3 to 18 years with severe and long-standing asthma. In most cases (70% a striking improvement of the general condition was achieved with complete regression or alleviation of dyspnoeic attacks. In 15 out of 17 children prednisone could have been withdrawn. No side effects were noted. In 4 children administration of Becotide or Beclomet was not possible.

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans

Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.

Topics: Adolescent; Albuterol; Asthma; Beclomethasone; Bronchi; Child; Drug Combinations; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride

We studied the clinical effect of a combination aerosol containing salbutamol and beclomethasone dipropionate in comparison to doubling the standard dose of salbutamol from an inhaler. Fifty-seven patients completed the double-blind, crossover study. They were treated with either an aerosol of 100 micrograms beclomethasone dipropionate and 200 micrograms salbutamol or 400 micrograms salbutamol alone. Both regimens were administered four times a day for 4 weeks. The patients showed significant improvement in FEV1, PEFR, and symptom scores after treatment with beclomethasone dipropionate and salbutamol compared with pre-trial values and with treatment with double the dose of salbutamol. The patients demonstrated a clear preference for treatment with the combination of beclomethasone dipropionate and salbutamol. Regular treatment with beclomethasone dipropionate in addition to salbutamol as a combination inhaler provides much better control of asthma than merely increasing the dose of salbutamol in those patients poorly controlled on standard doses of inhaled bronchodilators.

Topics: Adolescent; Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

Sixteen patients suffering from bronchial asthma, with or without chronic bronchitis, sufficiently severe to be treated with inhaled corticosteroids, were studied in a single-blind trial (blind observer) of beclomethasone dipropionate (BDP) given in three randomized dosage regimens: 500, 1000 and 2000 micrograms per day, each for 4 weeks. The beta 2-adrenergic agonist response curve showed a dose-dependent increase in FEV1 which was not affected by different doses of BDP. A small but significant reduction in basal cortisol levels was observed after BDP 500 micrograms/day. There was no significant difference between the various doses of BDP in reducing cortisol level and stimulation with tetracosactide remained unchanged. The study showed a gradual, dose-dependent improvement in lung function, statistically significant for morning peak expiratory flow rate at BDP 2000 micrograms/day. Dyspnoea score and beta 2-agonist use decreased, reflecting the anti-asthmatic effects. An increase in total leukocyte count was observed, together with a decrease in the eosinophil count. Oral candidiasis was seen in 2 out of 16 patients. It is concluded that the clinical anti-asthmatic effects of corticosteroid treatment by inhalation are not due to modulation of beta 2-receptor function in the airways.

Topics: Adrenal Glands; Adult; Albuterol; Asthma; Beclomethasone; Blood Glucose; Bronchi; Dose-Response Relationship, Drug; Eosinophils; Female; Forced Expiratory Volume; Humans; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Receptors, Adrenergic, beta

To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 micrograms bid), high dose beclomethasone aerosol (1000 micrograms bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (+/- SE) value of FEV1 4 h after exposure to TDI was 2.6 +/- 0.17 L, which went to 3.3 +/- 0.12 after low dose beclomethasone, and to 3.5 +/- 0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P less than 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Methacholine Compounds; Middle Aged; Toluene 2,4-Diisocyanate

A recent case report suggested that hydroxychloroquine had a steroid sparing effect in a patient with severe chronic asthma. We have studied the effect of hydroxychloroquine in a group of nine steroid dependent adult asthmatic patients using a randomised double blind crossover comparison of hydroxychloroquine and placebo. Each patient received hydroxychloroquine (400 mg/day) or placebo for 2 month periods. The effect of hydroxychloroquine or placebo on asthma control was assessed by change in steroid dosage, visual analogue symptom scores, response to beta 2 agonist and peak expiratory flow rate (PFR) measurement. The dose of prednisolone required during hydroxychloroquine treatment did not differ from that during placebo treatment or in pre-trial period. There was no significant change in symptom scores of PFR measurement. In this study an 8 week treatment with hydroxychloroquine was of no benefit to patients with chronic steroid dependent asthma.

Topics: Adult; Asthma; Beclomethasone; Double-Blind Method; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Steroids

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Betamethasone; Bronchi; Clinical Trials as Topic; Drug Combinations; Female; Humans; Male; Middle Aged; Time Factors; Triamcinolone

Thirty one children with asthma were treated with inhaled beclomethasone and budesonide in a randomized cross-over study of 2 x 6 weeks' duration. The excretion of free cortisol in two 24 hour urine samples, collected at the end of each treatment period, was significantly higher (mean = 76.3 nmol per day) during budesonide treatment than during beclomethasone treatment (mean = 53.7 nmol per day) (p less than 0.01). The difference between the two drugs was more pronounced in the eight children who received 1,000 and 1,200 micrograms per day than in the 22 children who received 800 micrograms per day. Four children had cortisol excretion below the normal range when treated with beclomethasone. This was seen in one child during budesonide treatment. The age of the child did not influence the result. The long term clinical significance of these findings has yet to be elucidated.

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Hydrocortisone; Male; Pregnenediones; Random Allocation

To examine the effect of corticosteroids on bronchial hyperresponsiveness, a randomised, double dummy, single blind crossover study was performed in 18 subjects with chronic asthma, comparing the effect of three weeks' treatment with inhaled beclomethasone dipropionate, 1200 micrograms daily, and oral prednisone 12.5 mg daily. The 12 week study began with a three week run in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a three week washout period. Patients kept daily Airflometer readings and attended the laboratory every three weeks for spirometry and a histamine inhalation test for determining the provocative dose of histamine causing a 20% fall in FEV1 (PD20). The mean FEV1 at the start was 1.9 litres (56% predicted). There was no significant change in PD20 with prednisone treatment, the mean PD20 being 0.56 and 0.59 mumol before and after treatment. There was, however, a significant improvement in PD20 with beclomethasone dipropionate treatment, the geometric mean PD20 being 0.38 and 1.01 mumol before and after treatment (p less than 0.001). There was a small but significant improvement in mean FEV1 after beclomethasone dipropionate treatment--from 1.9 to 2.2 litres--but no change after prednisone. Both medications produced significant and similar improvements in morning and evening Airflometer readings, post-bronchodilator improvement, and diurnal variation. Thus at doses that had similar beneficial effects on lung function beclomethasone dipropionate caused a significant improvement in bronchial hyperresponsiveness whereas prednisone caused no change. The superior topical anti-inflammatory effect of beclomethasone dipropionate may account for the different effects on bronchial hyperresponsiveness.

Topics: Administration, Inhalation; Administration, Oral; Adult; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Prednisone

An open parallel study lasting 24 weeks was performed in 39 asthmatics to evaluate patient compliance and the clinical effects of regular inhalations of beclomethasone dipropionate and salbutamol used simultaneously from a combination inhaler with regular inhalations of salbutamol and beclomethasone dipropionate used sequentially from separate inhalers. Total daily doses in the two groups were 800 micrograms salbutamol and 400 micrograms beclomethasone dipropionate. There were no differences between the two treatment groups with respect to clinic pulmonary function tests (FEV1, FVC), daily PEF measurements, symptom scores, use of symptomatic bronchodilator therapy, requirements for extra medication and patients' and physician's assessment of treatment. At 12 weeks, the physician assessed significantly more patients to have better symptom control on the combination inhaler than on separate inhalers. Patient compliance was high in both treatment groups which may have been due to the close supervision of the clinical study.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Asthma; Beclomethasone; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Respiratory Function Tests

A six-month double-blind controlled trial compared a 2,000 microgram per day dose of beclomethasone dipropionate aerosol (BDP), with current upper level doses of 800 micrograms per day of the standard BDP, in asthmatics requiring oral corticosteroids in addition to BDP and bronchodilators. Both groups showed a significant reduction in their oral steroid requirements during the study, with a 34 percent reduction in the lower dose group and a 57 percent reduction in the high dose BDP group while maintaining good symptomatic control of asthma; there was an associated improvement in baseline serum cortisol levels. Over the same period, the pulmonary function of the lower dose group showed significant worsening relative to that of the group receiving the high dose BDP which improved. There was no increase in dysphonia or oropharyngeal candidiasis among those using the concentrated BDP. We conclude that high dose concentrated BDP appears to be a safe medication in long-term steroid-dependent asthma, and is effective in reducing dependence on the use of oral corticosteroid with associated improvement both in pulmonary and adrenal function.

Topics: Administration, Inhalation; Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Random Allocation; Time Factors

The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test. The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites measured by gas chromatography. The adrenal response to adrenocorticotropic hormone stimulation was unaffected by treatment or dose. The unstimulated diurnal production of glucocorticosteroids demonstrated a highly significant dose-related suppression in response to the inhaled steroids. No significant difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether budesonide offers an improved ratio between beneficial anti-inflammatory effect and unwanted systemic activity.

Topics: Adolescent; Adrenal Cortex Function Tests; Androstenedione; Asthma; Beclomethasone; Budesonide; Child; Circadian Rhythm; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Male; Pituitary-Adrenal Function Tests; Pregnenediones; Prospective Studies; Random Allocation

To determine whether 4 drugs used in the treatment of asthma inhibit the late asthmatic reaction and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 24 sensitized subjects divided into 4 groups. Beclomethasone aerosol (1 mg bid), slow-release theophylline (6.5 mg/kg bid), slow-release verapamil (120 mg bid), and cromolyn (20 mg qid via spinhaler), were administered for 7 days, respectively, to 1 of the 4 groups, according to a double-blind, crossover, placebo-controlled study design. When the subjects were treated with placebo, verapamil, or cromolyn, FEV1 markedly decreased and airway responsiveness increased after exposure to TDI. By contrast, beclomethasone prevented the late asthmatic reaction and the associated increase in airway responsiveness to methacholine induced by TDI. Slow-release theophylline partially inhibited both the immediate and the late asthmatic reactions but had no effect on airway hyperresponsiveness to methacholine. These results suggest that only high-dose inhaled steroids can completely block TDI-induced late asthmatic reactions.

Topics: Asthma; Beclomethasone; Bronchial Provocation Tests; Clinical Trials as Topic; Cromolyn Sodium; Cyanates; Delayed-Action Preparations; Double-Blind Method; Forced Expiratory Volume; Humans; Immunization; Lung; Methacholine Chloride; Methacholine Compounds; Placebos; Random Allocation; Respiratory System; Theophylline; Time Factors; Toluene 2,4-Diisocyanate; Verapamil

Nedocromil sodium is a new antiasthmatic drug with properties similar to sodium cromoglycate. We examined the efficacy of nedocromil sodium compared to placebo in 71 asthmatic patients in a three-centre double-blind parallel group study over 12 weeks. During the study the patients' maintenance inhaled corticosteroids were progressively withdrawn. Nedocromil sodium had an advantage over placebo in the number of withdrawals related to uncontrolled asthma, 14 and 24 respectively (p = 0.03). Changes in symptom scores, peak flow rates and bronchodilator use favoured nedocromil sodium occasionally during the study. The unusual taste of the active drug was reported frequently. Nedocromil sodium is more efficacious than placebo in asthma maintenance, but does not replace inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Nedocromil; Pulmonary Ventilation; Quinolines

An open long-term trial of inhaled beclomethasone dipropionate was carried out in 32 asthmatic patients chronically dependent on systemic corticosteroids. Our objectives were to study the efficacy and safety of beclomethasone and to determine the proportion of patients in whom systemic steroids could be replaced by the new drug. All subjects had a clear history and physical findings of asthma as well as significant improvement in respiratory function after inhalation of salbutamol. Patients were followed for 4 to 8 years. Compared with a baseline period, patients receiving beclomethasone had reduced symptoms and needed less bronchodilator therapy, but their pulmonary function was unchanged. Bronchial biopsy specimens from seven patients who had been taking beclomethasone for as long as 8 years did not differ histologically from specimens from five asthmatic patients who had never taken the drug. Nine patients were able to stop taking systemic corticosteroids within 9 months, eight required them occasionally, and in eight the requirement was substantially reduced; the requirement did not change appreciably in the remaining seven. Inhaled beclomethasone is a safe and effective drug for chronic administration to asthmatic patients, and in 78% of our subjects the need for systemic steroids was substantially reduced or eliminated.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Beclomethasone; Biopsy; Bronchi; Clinical Trials as Topic; Female; Humans; Long-Term Care; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Safety; Substance-Related Disorders

The efficacy of beclomethasone dipropionate (BDP) was compared with sodium cromoglycate (SCG) and placebo in a double-blind parallel group study of 30 asthmatic children over a two-month period. All the three treatment groups received salbutamol concomitantly. Lung volumes, airway mechanics and the nonspecific bronchial hyperreactivity to carbachol were measured at the beginning and the end of the study. Two patients were excluded because of unequal clinical conditions at the entry and the end of the study and three because of lack of co-operation. Three patients (1 on SCG, 2 on placebo) dropped out because of worsening clinical symptoms. The improvement in airway mechanics shown by the group treated with BDP (n = 7) was significantly greater (p less than 0.01) than in the group treated with SCG (n = 8). Nonspecific hyperreactivity to carbachol improved significantly in the BDP group (factor 5.9) compared to the SCG group (factor 1.9). Childhood asthma seems to be better controlled by a combination of BDP and salbutamol, than by SCG and salbutamol.

Topics: Administration, Inhalation; Adolescent; Airway Resistance; Asthma; Beclomethasone; Bronchi; Carbachol; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Female; Humans; Lung Volume Measurements; Male

Single-dose salbutamol (200 micrograms), beclomethasone dipropionate (200 micrograms), and sodium cromoglycate (SCG) (10 mg) administered by inhalation 10 minutes before allergen challenge were examined with regard to inhibition of allergen-induced early (EAR) and late (LAR) asthmatic responses and allergen-induced increase in bronchial responsiveness to inhaled histamine. Ten atopic subjects with asthma participated in a blinded, crossover, placebo-controlled trial. The EAR was inhibited by salbutamol and SCG but not by beclomethasone dipropionate or placebo (p less than 0.01). The LAR (p less than 0.01) and the allergen-induced increased bronchial responsiveness to histamine 7 hours (p less than 0.01) and 30 hours (p less than 0.05 and p less than 0.01 for various comparisons) were inhibited by SCG and beclomethasone diproprionate but not by salbutamol or placebo. The allergen-induced LAR and associated increased responsiveness are now believed to be more important clinically than the EAR. The clinical relevance of these results is to stress the importance of the prophylactic nonbronchodilator drugs (SCG and steroids) and the potential inadequacy of bronchodilators used alone in the treatment of both perennial and seasonal allergic asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Allergens; Asthma; Beclomethasone; Bronchi; Bronchial Diseases; Bronchial Provocation Tests; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Female; Histamine; Humans; Male; Time Factors

After a run-in period of 2 weeks, receiving a regimen of inhaled beta 2-agonists and/or theophyllines, 38 atopic patients with asthma with perennial symptoms were randomly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate (SCG), 2 mg four times daily, and placebo beclomethasone dipropionate (BDP), or BDP, 200 micrograms twice daily, and placebo SCG. After crossover, each group received the opposite treatment for the final 8 weeks. FEV1, FVC, and provocation concentration of histamine causing a 20% fall in FEV1 (PC20) were determined monthly and peak expiratory flow (PEF) daily throughout the study. A significant increase in FEV1, FVC, and PEF (p less than 0.01) was observed after BDP treatment was started, and likewise, in the second period, an increase in both FEV1 and PEF (p less than 0.05) was observed. The total effect on logarithm-natural (Ln) (PC20), i.e., the mean effects of the two periods, was also significant (p less than 0.01). SCG, however, was most effective when it was used as the first drug, indicated by a significant increase in FVC in the first period (p less than 0.05). Neither in the first nor in the second period did SCG treatment influence the Ln (PC20) value positively, and the SCG treatment administered in the second period could not maintain the improvement in the pulmonary function (i.e., FEV1, FVC, and PEF) obtained initially with the BDP treatment. When the effect of BDP on FEV1, FVC, PEF, and Ln (PC20) was compared to the effect of SCG in the first 8-week treatment period, no significant difference was observed (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Asthma; Beclomethasone; Bronchi; Cromolyn Sodium; Female; Humans; Lung; Male; Spirometry

The objective of this study was to compare the clinical effects of beclomethasone dipropionate (BDP) and budesonide in asthmatic children using two common ways of administration. Twenty-one children, aged 4-14 years, who regularly used inhaled corticosteroids for their control of asthma were included in the study. The drugs were studied by using a double-blind randomized cross-over design trial with a single-blind placebo period at the end. Each period lasted 3 weeks. The dosage was 100 micrograms b.i.d. for both drugs. Budesonide was administered via a spacer inhaler (Inhalet), and beclomethasone dipropionate via a standard actuator. Compared with placebo, both drugs significantly improved PEFR values for morning (20% for budesonide and 14% for BDP) and evening (14% for budesonide and 9% for BDP). Both morning and/or evening peak flows were significantly higher during the budesonide treatment as compared with the BDP treatment. In comparison with the placebo period, FEV1.0 was significantly improved with budesonide but not with BDP. Plasma cortisol, WBC counts, differential and eosinophilia counts in blood were determined at the beginning and the end of each period. All of the values except for the eosinophil counts were within normal ranges. Candida was looked for but not found in any case. No other adverse effects were registered. For most of the children, a deterioration of the state of their asthma and increased need for concomitant therapy during the placebo period confirmed their steroid dependence. The number of administrations with concomitant anti-asthmatic therapy increased during placebo by 61% as compared with the budesonide therapy, and by 40% compared with the BDP therapy.

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Pregnenediones; Random Allocation

To test the hypothesis that patients with asthma who develop cough and wheezing after the use of beclomethasone aerosol would have a better tolerance for triamcinolone aerosol.. Randomized, double-blinded, crossover trial.. Pulmonary function laboratory.. Volunteer sample of 24 patients attending an asthma clinic who had developed cough, with or without wheezing, after inhaling beclomethasone aerosol. All patients completed the study.. Aerosols were used in habitual manufacturers' preparations and canisters, but both were administered in three puffs through the delivery system used for triamcinolone. The preparations differed in drug (beclomethasone dipropionate or triamcinolone acetonide), propellant (trichloromonofluoromethane and dichlorodifluoromethane, or dichlorodifluoromethane alone, respectively) and dispersant (oleic acid or dehydrated alcohol, respectively). PATIENTS inhaled three puffs of one aerosol on one day and three of the other on the next.. Forced expiratory volume in one second (FEV1) was measured before and after each aerosol application. The FEV1 decreased a mean of 17.7% from baseline after inhalation of beclomethasone, and 0.8% after triamcinolone (difference, 16.9; 95% confidence limits, 12.36 to 21.34; p less than 0.001). Coughs were counted after each puff. The mean number of coughs after beclomethasone aerosol inhalation was 35.8, and after triamcinolone, 0.5 (difference, 35.3; 95% confidence limits, 22.62 to 47.98, p less than 0.001).. Asthmatic patients who are unable to inhale beclomethasone aerosol due to cough or wheezing can inhale triamcinolone aerosol without difficulty. Our investigation does not determine the exact cause of the coughing and wheezing with the beclomethasone aerosol, but we suspect the dispersant as the source.

Topics: Adult; Aerosol Propellants; Aerosols; Aged; Asthma; Beclomethasone; Cough; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Respiratory Sounds; Triamcinolone Acetonide

The purpose of the study was to evaluate the efficacy of a structured education program on knowledge and psychomotor skills of subjects using inhaled beclomethasone dipropionate. The sample was comprised of 26 male outpatients with a mean age of sixty years (range 49-69 yrs) and mean educational level of 11 years (range 7-18 yrs). Subjects were tested to assess knowledge of drug action, self-administration, and side effects. Skill in self-administration was assessed by two independent raters who were blind to group assignment. Then, patients were randomly assigned to an experimental group (n = 13), who received a structured educational program, or a control group (n = 13), who received no structured educational interventions. Patients were retested four weeks after randomization. Subjects in the experimental and control groups did not differ significantly with respect to their initial mean knowledge and performance scores. The post-test mean knowledge score was significantly higher when compared to initial score for each group. Mean knowledge score at post-test did not differ significantly between groups. However, when comparing post-test performance scores to initial scores the experimental group had a significantly greater increase in mean score than the control group. It is concluded that a structured patient education program is an effective method for improving the psychomotor skills necessary for proper use of beclomethasone dipropionate aerosol.

Topics: Aerosols; Aged; Asthma; Beclomethasone; Educational Measurement; Evaluation Studies as Topic; Humans; Male; Middle Aged; Outcome and Process Assessment, Health Care; Patient Education as Topic; Psychomotor Performance; Self Administration; Substance-Related Disorders

Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 micrograms twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 micrograms twice daily.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Beclomethasone; Budesonide; Child; Double-Blind Method; Humans; Pregnenediones; Random Allocation

In a double-blind crossover study, we compared the relative effects of inhaled beclomethasone dipropionate (BDP) 800 micrograms per day and oral theophylline on the severity of bronchial hyperresponsiveness (BHR) to histamine. Daily doses of theophylline were sufficient to keep serum levels between 55 and 110 mumol/L. The subjects were 26 patients with severe asthma whose symptoms were inadequately controlled by regular treatment with inhaled salbutamol. The severity of BHR improved within 3 wk in the group treated with BDP, whereas no change occurred in the group treated with theophylline. There were no significant changes in FEV1 in either group during the study. When BDP was changed to theophylline there was a deterioration in BHR. Aerosol steroids, rather than theophylline, are the treatment of choice when reduction in the severity of BHR is the aim of treatment in patients with severe asthma.

Topics: Adult; Aerosols; Airway Resistance; Asthma; Beclomethasone; Bronchi; Bronchial Provocation Tests; Delayed-Action Preparations; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Theophylline

A double-blind crossover study lasting 16 weeks was carried out in children with chronic extrinsic asthma to compare the clinical effects of regular inhalations of salbutamol and beclomethasone dipropionate from a combination inhaler and regular inhalations of the same two drugs used sequentially from separate inhalers. Eighteen patients entered the study and 16 completed both 8-week treatment periods. However, there was a large amount of missing data, with only 9 complete sets of paired data; efficacy analyses were performed on data from 10 patients on separate inhaler therapy and from 14 patients on combination inhaler therapy. There were no significant differences between daily peak flow rate measurements, symptom scores, additional symptomatic bronchodilator therapy, acute exacerbations of asthma or incidence of adverse events, demonstrating that both treatments were similarly effective in controlling the patient's asthmatic symptoms. There was, however, a trend for higher peak flow values and lower symptom scores on separate inhaler therapy in this small group of asthmatic children. Although the results suggest that regular therapy using a combination inhaler is as effective as sequential administration of salbutamol and beclomethasone dipropionate from separate inhalers, it is concluded that the study should be extended to a larger group of patients to determine whether there might be any statistically significant differences between the two regimens.

Topics: Adolescent; Albuterol; Asthma; Beclomethasone; Child; Double-Blind Method; Drug Combinations; Female; Humans; Male; Nebulizers and Vaporizers

Cough and wheezing are frequent side effects of inhaling beclomethasone dipropionate aerosol (BA) in patients with asthma. Twenty percent of our outpatient asthmatic subjects are unable to take BA due to these side effects. Twelve patients with history of severe cough and wheezing after inhaling BA were tested. Three puffs of either BA or placebo (Plc) were administered from a metered dose inhaler (MDI) in a double-blind crossover design. They coughed a mean of 31 times after BA and 19 times after Plc. Forced expiratory volume in one sec (FEV1) declined a mean of 22.6 percent after BA and 22.0 percent after Plc. Pretreatment with albuterol attenuated both the cough and the drop in FEV1. Follow-up study showed that regular pretreatment with bronchodilator enabled seven of 12 patients to tolerate BA therapy. The remaining five required a short course of increased dose oral steroid therapy. Cough and wheezing are frequent side effects of BA therapy that interfere with regular compliance. Pretreatment with a bronchodilator is effective in attenuating these side effects in some patients; in others, a short course of oral steroid therapy may be necessary.

Topics: Aerosols; Albuterol; Asthma; Beclomethasone; Cough; Double-Blind Method; Forced Expiratory Volume; Humans; Respiratory Sounds

Chronic nonsteroid-dependent childhood asthma was treated by adding beclomethasone dipropionate (BDP) or placebo (P) to the daily regimen of theophylline (T). Subjects (6-12 years) were selected based on daily control of asthma by T at necessary T levels in sera of 10-20 micrograms. Active BDP (200 micrograms b.i.d.) and P groups were randomly assigned. Each subject's baseline values were evaluated on a 4-week open phase followed by a 10-12 week double-blind phase. Daily diaries were kept for signs, symptoms, Wright peak flow recordings, and medication requirements. Visits were monitored for urine and serum cortisols, pulmonary function tests (PFT), objective changes, and medication compliance. Demographics between both groups were nonsignificant (NS). Baseline PFTs in P group were significantly better than the BDP group. Serum and urine cortisols and ACTH responses were NS (p less than 0.05). Drug efficacy for asthma characteristics was significantly improved in the BDP group (p less than 0.05) only. The BDP group maximized their response by 8 weeks, with improvement of their FEV1 and FEF25-75 PFT. Thus, b.i.d. BDP provided good asthma control and the twice-daily program should insure improved compliance.

Topics: Adrenergic beta-Agonists; Asthma; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Random Allocation; Respiratory Function Tests; Theophylline

Topics: Administration, Oral; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Humans

The efficacy of twice daily inhaled beclomethasone dipropionate administered by a concentrated aerosol inhaler (one puff twice daily-500 micrograms/day) has been compared with that of treatment four times daily with a standard dose inhaler (two puffs four times daily-400 micrograms/day) in 21 patients with stable asthma. Double placebo inhalers were used in a randomised crossover fashion during two four week treatment periods. Mean peak expiratory flow (PEF), mean symptom scores, and number of extra salbutamol inhalations required were not significantly different between the two treatment periods. Local side effects were more common during treatment with the four times daily active preparation; overt oropharyngeal candidiasis, however, was not found in either group during the study. On completion of the crossover study patients were transferred to the twice daily regimen. At the three month follow up all patients had remained stable and the outpatient PEF was significantly higher (mean 382 (SD 26)l min-1) than at entry into the trial (mean 345 (24)l min-1) (p less than 0.05). Twice daily beclomethasone administered by a concentrated aerosol inhaler appears to be as effective as the standard four times daily regimen in controlling stable asthma.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Random Allocation

Twenty nine young children with severe recurrent asthma were given nebulised beclomethasone dipropionate or normal saline in a double blind manner over a six month period. Progress was monitored using diary score cards. Those receiving beclomethasone had lower symptom scores, had more symptom free days, and required less additional treatment with bronchodilator agents. The code needed to be broken more frequently if normal saline was used. Over the study period height and weight increases in the two groups were similar, and no serious side effects were noted.

Topics: Aerosols; Asthma; Beclomethasone; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infant; Male; Random Allocation

Topics: Adult; Aerosols; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Humans; Pregnenediones

Substitution of aerosolized triamcinolone acetonide for aerosolized beclomethasone dipropionate in treatment of 30 chronic asthmatics resulted in subjective improvement in all patients. There was reduction in requirement of systemic steroids and inhaled beta adrenergics. No adrenal suppression or oropharyngeal candidiasis occurred after replacing beclomethasone dipropionate with triamcinolone acetonide.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Respiratory Function Tests; Triamcinolone Acetonide

The effects of controlling childhood asthma of the same daily dose (400 micrograms) of beclomethasone dipropionate, given in two or four equal divided doses from a metered aerosol, were compared in a double blind crossover study. Thirty one children aged 6-14 years completed the study. They had previously been shown to need beclomethasone by showing either symptoms or reduced peak flow when the treatment was withdrawn. They recorded their daytime and night time symptoms on a visual analogue scale and their morning and evening peak expiratory flow (PEF), and recorded their symptomatic use of bronchodilator aerosols. Spirometry was performed at the end of each treatment period. Control of asthma was good on both regimens. There were small differences in both objective and subjective measurements in favour of the four times daily regimen, but none reached statistical significance, apart from patients' assessment of daytime wheeze (p less than 0.05). In particular, the differences in the results of lung function tests were very small. Compliance was better for morning and evening doses. These results suggest that beclomethasone given as 200 micrograms twice daily is effective in controlling mild childhood asthma. It may be preferable to 100 micrograms four times daily because of better compliance and because it is unnecessary to take medication to school.

Topics: Adolescent; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male

We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion. Three children withdrew due to deterioration while on placebo. Of the remaining 13, eight were better on beclomethasone and five on placebo. These trends in favour of nebulised beclomethasone were not significant and do not suggest that the suspension is as effective as inhaled powder or aerosol topical steroid formulation.

Topics: Asthma; Beclomethasone; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infant; Male; Nebulizers and Vaporizers; Suspensions

In a double-blind cross-over study beclomethasone dipropionate inhaled as a dry-powder in a dose of 400 micrograms twice daily was compared with a conventional aerosol in a dose of 100 micrograms four times daily in 16 outpatients with chronic asthma. Each of the 2 treatments lasted for 4 weeks. There was no significant difference with respect to daily peak expiratory flow rates, symptom scores, bronchodilator usages and other lung function measurements between the 2 treatments. Tetracosactrin tests were within normal limits and no clinical oral candidiasis was observed throughout the study. In conclusion, beclomethasone dipropionate dry-power given twice daily was effective for the control of asthma and could be recommended for patients with poor drug compliance.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Lung Volume Measurements

Twenty eight patients with chronic asthma took part in a double blind single crossover controlled trial of inhaled budesonide and inhaled beclomethasone dipropionate, using high doses of 1600 micrograms and 1500 micrograms daily respectively. Both drugs were administered by pressurised aerosol inhaler; the inhaler containing budesonide and its matching placebo were fitted with a collapsible spacer device. There was no significant difference in the control of asthma during the two six week treatment periods. There was no significant difference in FEV1 and forced vital capacity after four and six weeks of treatment or in mean morning and evening peak expiratory flow rates for the last 21 days of treatment. There was a small but statistically significant reduction in the daytime wheeze score while they were taking high dose budesonide but there was no difference for daytime activity, cough, and night symptoms. The mean basal cortisol concentrations were significantly lower after six weeks of high dose treatment than before treatment (budesonide p less than 0.01, beclomethasone p less than 0.05). There was no difference between mean basal cortisol values after six weeks of high dose treatment, and there was no effect on the rise of cortisol obtained after a short tetracosactrin test. High dose inhaled corticosteroids produced few side effects and were well tolerated.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Pregnenediones; Prospective Studies

An open, crossover study lasting 8 weeks was performed to establish if a twice daily regimen of combined inhalation of salbutamol and beclomethasone dipropionate from a single inhaler was as effective in controlling asthma as the 4-times daily regimen. The results from these two treatment periods were compared with an initial 4-week baseline period when all patients received the same agents from separate inhalers on a 4-times daily dose schedule. Twenty stable asthmatics were entered into the study and 19 completed the three treatment periods. The clinic lung function data, symptomatic inhaler usage, requests for additional therapy and physician's subjective assessment of treatment showed that all three treatment regimens were similarly effective in managing the patients' asthma. There was no significant difference between the mean PEFR measurements taken 4 times each day between the two treatment regimens of the combination inhaler. However, except for PEFR in the afternoon, the mean values for both treatment schedules of the combination inhaler were significantly greater (p less than 0.05) than those during the separate inhaler baseline period. More than half the patients considered that both treatment schedules of the combination inhaler provided better control of their asthma than treatment with the separate inhalers, and the majority preferred the twice daily regimen to the 4-times daily regimen. The results, overall, showed that in stable asthmatics the combined administration of salbutamol and beclomethasone dipropionate from one inhaler provides significantly better therapy than the same agents from separate inhalers and that the twice daily dose schedule of the combination inhaler is equally as effective as a 4-times daily regimen.

Topics: Adult; Aged; Albuterol; Asthma; Beclomethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Maximal Expiratory Flow Rate; Middle Aged

The currently available beclomethasone dipropionate (BDP) metered-dose nasal aerosol spray is considered uncomfortable by some patients because of the force of delivery. It was compared for efficacy and acceptability in a double-blind study with a new aqueous suspension BDP spray for the treatment of seasonal allergic rhinitis in 44 symptomatic patients aged 12 to 43 years. After 7 days of baseline evaluation, every patient was given both an aerosol canister and an aqueous spray bottle each containing either BDP, 42 mcg per spray, or placebo (P). For 15 days the patient sprayed each nostril twice a day with one spray of suspension (BDP or P) followed 5 minutes later by one spray of aerosol (P or BDP). Patients were evaluated before the study medications were started (day 1) and on days 4, 8, and 15 for nasal and eye symptoms. Nasal cytologic specimens were examined on days 1 and 15, and rhinomanometry was performed on days 1, 8, and 15 of the study. Topical BDP by both methods of delivery was rapidly effective in decreasing mean nasal obstruction, rhinorrhea, sneezing, and itching symptoms as well as mean eye symptoms with no statistically significant differences between them. Nasal airflow increased with both treatments; rhinomanometry significantly correlated with subjective nasal obstruction scores. Of 34 patients with nasal eosinophils, 74% had fewer eosinophils after treatment. Most patients (84%) preferred the aqueous spray over the pressurized aerosol.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Allergens; Asthma; Beclomethasone; Humans; Nasal Mucosa; Pollen; Rhinitis, Allergic, Seasonal

Twice-daily and four-times daily treatment with beclomethasone dipropionate aerosol were compared in a double dummy crossover study in patients with severe chronic bronchial asthma. The trial consisted of two two-month treatment periods preceded by a two-week baseline period. No significant difference was found in the morning or evening PEF, in symptom scores for wheeze, cough, sputum, sleep disturbance, limitation of daily activity, rhinitis, daily usage of bronchodilator aerosol or requirement for additional oral corticosteroids. The study has confirmed that in management of severe bronchial asthma, a twice-daily regimen of beclomethasone dipropionate aerosol is as effective as four-times daily treatment, if the total daily dose of beclomethasone dipropionate is kept unchanged.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Chronic Disease; Female; Humans; Male; Middle Aged; Random Allocation; Time Factors

Topics: Adult; Albuterol; Asthma; Beclomethasone; Circadian Rhythm; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Respiratory Therapy

The effect of the simultaneous administration of salbutamol and beclomethasone dipropionate, from a combination inhaler, was compared with the same doses given with an interval of 10 min, from separate inhalers, in a group of 40 asthmatic females. The double-blind parallel-group study was well balanced and lasted 4 weeks. Both groups showed a similar improvement in thrice-weekly lung function values and daily symptoms in week 4 compared to week 1. There were no other differences and no adverse reactions. The combination inhaler is a useful alternative for maintenance treatment in patients who require an inhaled steroid.

Topics: Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Middle Aged; Respiratory Function Tests

Atopic asthma is associated with diminished cell-mediated immunity and elevated levels of IgE, both of which may be caused by imbalances of T-lymphocyte subsets. We analyzed the response of peripheral blood T-cell subsets to two commonly used corticosteroid preparations as a probe of T-cell subset regulation. We administered prednisone (P) 60 mg or 20 mg, beclomethasone dipropionate (BDP) aerosol, 336 micrograms, placebo, or BDP vehicle in a double-blind protocol to 15 atopic asthmatic patients and ten nonatopic subjects. No difference was found between the groups of the baseline number of T-cells with T4, T8, M1, and Ia antigens, nor the ratio of T4+ (helper) to T8+ (suppressor) cells. Five hours after administration of BDP aerosol, BDP vehicle, and oral placebo, there was no change of these values in either the atopic or in the nonatopic group. In contrast, P, 20 and 60 mg, caused a fall of T4/T8 ratio in the atopic, but not in the nonatopic population. Atopic asthma is not associated with baseline imbalances of peripheral blood T-cell subsets, but is associated with an abnormal response to systemic, but not inhaled corticosteroid.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Female; Humans; Hypersensitivity, Immediate; Leukocyte Count; Male; Prednisone; T-Lymphocytes

We investigated the possibility that corticosteroids can reduce bronchial responsiveness to histamine by mechanisms other than change in airway caliber. Ten adult asthmatic subjects were selected because their symptoms were controlled by bronchodilators alone, they had no recent respiratory infection or allergen exposure that might have temporarily altered responsiveness, their spirometry was more than 70% predicted, and they had a range of histamine bronchial hyperresponsiveness. They received, in random order and double-blind manner, beclomethasone dipropionate (400 micrograms daily) or placebo for 4 wk and then, after a 2-week washout period, they crossed over to the other treatment for 4 wk. Treatment with beclomethasone induced a small but significant reduction in bronchial responsiveness to histamine (p = 0.014). Although the improvement was too small to be considered of clinical significance, its importance lies in the mechanisms by which it was produced. Part of the improvement was related to improvement in airway caliber, but, even when the data was adjusted for this, there was still a significant difference between beclomethasone and placebo treatment (p = 0.018). The results suggest that regular treatment with corticosteroids can alter bronchial responsiveness through mechanisms other than change in airway caliber.

Topics: Adult; Analysis of Variance; Asthma; Beclomethasone; Bronchi; Clinical Trials as Topic; Female; Forced Expiratory Volume; Histamine; Humans; Male; Patient Compliance

In a short-term, open cross-over clinical efficacy study, inhalation of budesonide 800 micrograms once daily was compared to inhalation of budesonide 400 micrograms twice daily and beclomethasone dipropionate 200 micrograms four times daily in 20 patients with stable steroid-dependent chronic asthma. Budesonide was inhaled through a spacer tube. The drugs were given in 3-week periods. Clinical symptoms, consumption of beta 2-agonists and peak flow were measured. In all but one patient, the reduced frequency of budesonide inhalations to only once daily has not given significantly different results compared with more frequent inhalations.

Topics: Administration, Intranasal; Asthma; Beclomethasone; Budesonide; Chronic Disease; Clinical Trials as Topic; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones; Random Allocation

The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.

Topics: Adult; Aged; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Double-Blind Method; Humans; Middle Aged; Prednisolone; Pregnenediones; Random Allocation

A double-blind cross-over study lasting 16 weeks was conducted to establish if a twice daily regimen of beclomethasone dipropionate (BDP) was as effective in controlling asthma as a four times daily regimen. The patient's need for inhaled steroids (100 mcg BDP qds) was confirmed prior to entering the study by deterioration of peak expiratory flow rates and/or increased bronchodilator usage during a single-blind placebo period of 6 weeks. Thirty six asthmatics were eligible to enter the study and completed both treatment periods. Daily record cards of symptom scores, four times daily peak expiratory flow rate measurements and inhaled bronchodilator usage were recorded throughout the study. There was no significant difference between the mean PEFR measurements taken four times each day and the variability in PEFR, between the two treatment groups. Symptom scores for cough, wheeze, breathlessness and overall disability also showed no significant difference. Symptomatic inhaler usage for the two groups was similar. Lung function measurements of FEV1, FVC and VC were almost identical; FEV1 being 2.1 l on twice daily regimen and 2.2 l on four times daily regimen. A slight variation was observed in PEFR taken at the end of each treatment period at the clinic visits, being 361 l/min on twice daily and 380 l/min on four times daily drug dosage. In stable asthmatics, the control of asthma measured both symptomatically and by daily lung function was independent of dosing schedule, but twice daily treatment may well lead to better compliance.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

A compound consisting of a beta-stimulant, salbutamol (Ventolin; Allen & Hanburys) (100 micrograms/puff), and a steroid, beclomethasone dipropionate (Becotide; Allen & Hanburys) (50 micrograms/puff), was studied to test the hypothesis that the corticosteroid could enhance the bronchodilator properties of the beta-stimulant during chronic asthma and simulated acute attacks (antigen challenge). Conventional doses (200 micrograms and 100 micrograms of salbutamol and beclomethasone respectively) were compared using a schedule which included a second administration 1 hour later. The results obtained on the baseline bronchial responsiveness of chronic asthmatics and during the delayed asthmatic response (simulated acute asthma) were similar. The compound was as effective as salbutamol alone but not more so. A significantly greater bronchodilator response was recorded in all patients after the second administration of both the compound and salbutamol alone. The practical advantages of having one rather than two inhalers are evident, but the appropriate application of this compound agent, probably in a prophylactic role, must be defined.

Topics: Acute Disease; Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Lung Volume Measurements; Male; Middle Aged; Random Allocation; Time Factors

Ninety-nine patients, who had never previously taken inhaled steroids were enrolled in a randomized, single-blind, parallel study, the aim of which was to compare the efficacy and safety of flunisolide inhalation, 500 mcg twice daily, with beclomethasone dipropionate inhaler 100 mcg four times daily for the treatment of chronic asthma. The treatment period was for 6 weeks. The patients were examined clinically at entry, week 3 and week 6 and both treatment groups showed a marked improvement in almost all parameters during the course of the study. Flunisolide was statistically significantly superior to beclomethasone dipropionate for wheezing at week 6, coughing at week 6 and chest tightness at weeks 3 and 6. The number of asthma attacks per day decreased significantly more with flunisolide treatment than with beclomethasone dipropionate. The over-all evaluation of efficacy by both doctors and patients also showed flunisolide to be superior to beclomethasone dipropionate. In several other parameters there was a trend shown favouring flunisolide, and beclomethasone dipropionate did not show a superiority over flunisolide in any efficacy parameter. Both drugs were well-tolerated, with unpleasant taste being the most frequent complaint in the flunisolide group. No patient in either group withdrew from the study because of adverse events. In this study, flunisolide inhaler was more effective than beclomethasone dipropionate inhaler for the treatment of chronic asthma exhibited by patients who had never been treated with inhaled steroids.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Tolerance; Female; Fluocinolone Acetonide; Humans; Male; Middle Aged; Random Allocation

Fifty-two children 6 to 12 yr of age and 37 young adults 13 to 38 yr of age with moderate to severe extrinsic asthma requiring daily bronchodilators and who had been taking beclomethasone dipropionate (BDP) for at least 3 months were evaluated. All patients received their regular daily medications and BDP, 2 inhalations 4 times a day (q.i.d.) (total dose, 336 micrograms/day), for 2 wk; they were then randomized to receive either BDP or placebo aerosol, 4 inhalations twice a day (b.i.d.), with the same total dose/day as well as their regular medications, for 8 wk. Placebo patients deteriorated significantly by comparison with BDP patients in respiratory symptoms and pulmonary functions. More placebo than BDP patients ended participation in the study prematurely because of increasingly severe symptoms. In the 89 study patients, there were no significant differences in respiratory symptoms or pulmonary function measurements between the b.i.d. and q.i.d. dosage regimens in either pediatric or adult age groups. There were no significant changes in mean morning cortisol levels from baseline measurements to the end of the study period; at that time, all patients had a normal ACTH stimulation test. We conclude that BDP (336 micrograms/day) is as effective and safe for control of asthma symptoms with b.i.d. as with q.i.d. dosage schedules in pediatric and young adult patients.

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Double-Blind Method; Drug Administration Schedule; Humans; Placebos; Respiratory Function Tests

In 23 stable asthmatic patients sensitivity to inhaled beclomethasone dipropionate (BDP) was demonstrated during single blind gradual tapering off of BDP. After a 2 week stabilization period the patients were randomly allocated to receive either 4 puffs of 50 micrograms BDP twice daily (AM/PM) or 8 puffs of 50 micrograms once daily (AM). After 4 weeks the patients were crossed over. Fifteen patients preferred the twice daily regimen, 5 preferred once daily and 3 had no preference (p less than 0.05). During the once daily dosing regimen a decrease in morning and evening peak expiratory flow (p less than 0.05) and an increase in nighttime and daytime symptom score (p less than 0.05) was found, while the number of inhaled beta 2-agonist doses did not change significantly (p = 0.05). It is concluded that a twice daily regimen controls the asthmatic symptoms significantly better than a once daily regimen.

Topics: Administration, Topical; Asthma; Beclomethasone; Drug Administration Schedule; Humans; Peak Expiratory Flow Rate; Respiratory Therapy

Topics: Albuterol; Aminophylline; Asthma; Beclomethasone; Circadian Rhythm; Clinical Trials as Topic; Double-Blind Method; Humans; Prospective Studies

Topics: Aerosols; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Middle Aged; Pregnenediones

Nedocromil sodium (FPL 59002) is a pyranoquinoline dicarboxylic acid that has been developed for the management of bronchial asthma. We report the results of a double blind group comparative trial in which the disodium salt of nedocromil delivered by pressurised aerosol and a placebo were compared in the management of patients with a diagnosis of bronchial asthma who entered the double blind period on a minimum dose of beclomethasone dipropionate. In almost all the assessments of clinical activity nedocromil sodium was shown to be more effective than placebo. These include improvements in diary card symptom scores, reduction in concomitant use of a bronchodilator aerosol, and patients' and investigators' assessments of efficacy. Unwanted effects were few and mild. No patients were withdrawn from the trial.

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nedocromil; Quinolines

Fifteen patients with chronic asthma completed a double-blind cross-over trial during which they were treated with the same daily doses of salbutamol and beclomethasone dipropionate (BDP) from either a combination inhaler or two separate inhalers. Lung function was measured at the end of each treatment period and each patient kept a diary card throughout. Daily assessments of patients' symptoms and additional medication requirements were similar during both treatment periods. Peak expiratory flow rate (PEFR) recordings taken four times a day showed little diurnal variation during both periods. Mean PEFRs for the groups during a period of 2 weeks were similar for both treatments at all times. Overall daily mean PEFRs showed a trend in favour of the combination inhaler. There was a suggestion of greater variability in airway obstruction during the period when the separate inhalers were used, as assessed by the number of occasions that the PEFR was outside the range (overall daily mean +/- 15%). Lung function measurements at the end of each period showed a trend in favour of the combination inhaler which was clinically significant in terms of the forced expiratory volume in the 1st second and forced vital capacity. The combination inhaler provides an alternative in the management of asthma which is at least as effective as treatment with salbutamol and BDP from two separate inhalers.

Topics: Adolescent; Adult; Albuterol; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Respiratory Therapy

Forty children with childhood asthma were conducted through a double-blind cross-over study to compare the effect of 400 micrograms beclomethasone dipropionate administered as aerosol and powder (Rotacaps). Children with severe asthma derived more benefit from the steroid administered as aerosol judged from their peak flow performance in the morning, although neither evening peak flow nor symptom scores revealed any difference. It is concluded that the Rotacaps are an advantageous supplement to available medication for the treatment of asthmatic children, although it should be observed that, using equal amounts of BDP, powder administration seems less effective than aerosol.

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Double-Blind Method; Humans; Powders

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Budesonide; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

Twelve patients with chronic asthma received either high dose beclomethasone once a day or standard doses of beclomethasone three times a day in a double blind crossover trial to determine whether inhalation once a day would be sufficient. With the once a day regimen peak expiratory flow rates fell significantly, symptoms of nocturnal asthma increased, and two patients withdrew from the study because of worsening asthma. Whether control can be achieved with steroids inhaled once a day by simply increasing the total daily dose remains to be seen.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Middle Aged; Peak Expiratory Flow Rate

In a double-blind controlled crossover trial of inhaled disodium cromoglycate and beclomethasone dipropionate in juvenile asthma, beclomethasone produced higher therapeutic scores but significantly so in only two indices--wheeze-free days and morning peak flow rates. Combined treatment offered no advantage over beclomethasone alone. No side-effects were noted. The findings confirm other studies of cromoglycate and a steroid aerosol (betamethasone 17-valerate) but disagree with the only other comparative trial of cromoglycate and beclomethasone, in which both were found equally effective.

Topics: Adolescent; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Double-Blind Method; Female; Humans; Male

Twenty-one patients with frequently recurrent severe asthma were treated for 2 wk with placebo capsules and metaproterenol sulfate aerosol therapy followed by beclomethasone dipropionate aerosol therapy sequentially inhaled every 4 to 6 hr and for 2 wk with the same aerosols and aminophylline therapy added. Treatment was double-blind, and the therapy regimens were administered in a random sequence. Patients measured their PEFR at home before and after aerosol inhalation three times a day. The mean PEFRs before inhalation of aerosol were significantly higher when patients were receiving aminophylline therapy. In 86% of the patients, the mean PEFR that was measured after inhalation of metaproterenol sulfate was 11% greater when they were also receiving aminophylline therapy, but this difference was not significant. In 14% of the patients, however, postaerosol inhalation PEFRs were significantly higher (50% to 80%) after aminophylline therapy was added to aerosol therapy. PEFRs were always lowest in the early morning, regardless of the therapy administered. Therapy regimens that contained aminophylline were associated with less dyspnea but produced more adverse side effects and were more costly. Thus in most patients the favorable effect that aminophylline therapy produced by raising baseline PEFRs and attenuating dyspnea should be balanced against the adverse effects this medication also produced, since in most patients aminophylline therapy did not significantly enhance postinhalation PEFRs.

Topics: Aerosols; Aminophylline; Asthma; Beclomethasone; Drug Combinations; Female; Humans; Intubation, Intratracheal; Male; Metaproterenol; Middle Aged; Peak Expiratory Flow Rate

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Hydroxycorticosteroids

A randomised double-blind crossover study was undertaken in 25 patients with variable airflow obstruction to assess the benefit of separating the inhalation of beta-agonist aerosols and corticosteroid aerosols by a timed interval of more than five minutes. Twenty-two patients (11 men and 11 women) completed 12 weeks of study; they inhaled 200 micrograms salbutamol followed either immediately or after a timed interval by 100 micrograms beclomethasone dipropionate two to four times daily. Morning and evening peak expiratory flow rates, symptom scores, additional beta-agonist inhaler usage, and subjective responses on a visual-analogue scale were recorded throughout. Results from the two last four-week periods, with and without the interval between drugs, were analysed. No differences were found. It is concluded that the theoretical benefit of delaying corticosteroid inhalation until optimum bronchodilatation has been achieved with a beta-agonist is not demonstrable in outpatient practice.

Topics: Adolescent; Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Random Allocation; Time Factors

An inhalation therapy device which facilitates the use of hand-held inhaler delivered medications in infants and children has been employed on a trial basis with 17 severe asthmatic children. Using patients as their own control, the dependence on medications, office hospital and emergency room facilities before and after administration of therapy with CAIR chamber was compared. An approximate 50% improvement was noted in all parameters studied. Most notably, hospitalizations were decreased by 94% over a study period which represented 104 months of cumulative observation.

Topics: Albuterol; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Humans; Infant; Prednisone; Respiratory Therapy

Topics: Aerosols; Albuterol; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Therapy, Combination; Hemodynamics; Humans; Respiration

We studied 17 asthmatic patients complaining of coughing attacks, with or without asthma, when inhaling beclomethasone dipropionate aerosol (Becotide). Specific airway resistance (SRaw) was measured immediately after a maximal inspiration (MI) and after Becotide inhalation. The effect of a second inhalation of Becotide was measured 10 min after inhalation of salbutamol. MI and Becotide induced large, but transient, SRaw increases in all patients; in addition, the latter induced coughing reactions. After salbutamol pretreatment, Becotide inhalation did not increase SRaw but coughing usually persisted. In 6 patients only, the increase in SRaw after Becotide was larger than that observed after MI. In those patients, placebo and Aldecine (similar to Becotide except for the metering valve) aerosols induced SRaw increases similar to that observed after Becotide. These data suggest that Becotide-induced bronchoconstriction is mainly related to the deep breath required for the inhalation. Non-specific irritation of the airways was probably responsible for the additional bronchoconstriction noticed in some patients.

Topics: Aerosols; Airway Resistance; Albuterol; Asthma; Beclomethasone; Bronchial Spasm; Cough; Humans; Premedication

Topics: Administration, Topical; Adolescent; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Pregnenediones; Respiratory Function Tests

The blocking effects of inhaled beclomethasone dipropionate (BDP) and fluocortin butyl ester (FCB) on the immediate and late asthmatic reactions induced by inhaled allergen were studied in two trials. In the first, a double-blind cross-over trial compared BDP (800 micrograms daily as powder) with FCB 8 mg daily (1:20 by wt.-Formulation 1). The second trial was identical in design and compared FCB 8 mg daily (1:20) with FCB 8 mg daily as Formulation 2 (1:40). Known BDP, 400 micrograms daily by pressurized aerosol was studied at the end of the second trial. Allergen provocation was performed before and after 7 days treatment with each drug, with a 2-week interval between each drug. Overall, a blocking index for the immediate reaction of greater than 50% was obtained in ten of twenty patients (50%) using BDP, and five of twenty-one (25%) using FCB (P less than 0.01). The late reaction was blocked in nine of eleven (82%) instances on BDP, and four of fourteen (33%) on FCB. Contrary to earlier reports, inhaled corticosteroid agents used for several days prior to bronchial challenge, were found to block both the immediate as well as the late reaction in many individuals.

Topics: Administration, Intranasal; Allergens; Asthma; Beclomethasone; Bronchial Provocation Tests; Clinical Trials as Topic; Double-Blind Method; Fluocortolone; Forced Expiratory Volume; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Middle Aged

The protective effect of a new inhaled steroid, fluocortin butyl (FCB), was compared to that of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDP) in patients with extrinsic asthma by means of the allergen-inhalation challenge test. Three different groups of 12 patients each participated in the study. One group was treated with FCB and BDP, the two others with FCB and DSCG, all in a randomized crossover study plan. After an initial allergen challenge (FEV1 fall greater than 15%), the patients were allocated to either treatment for 7-10 days. A second challenge test was then carried out, followed by a washout period of 4 days. The treatments were then crossed-over, and a third allergen challenge was carried out at the end of the second treatment period. With BDP 5 of 12 patients were protected; with FCB, 6 of 12 in two groups and 8 of 12 patients in a third group. With DSCG 3 of 12 patients were protected in the group in which the last medication was given 12 h before challenge, and 8 of 12 patients in the second group in which medication was given 1-2 h before challenge. In the same groups on FCB no such time-dependent effect was observed. No statistically significant differences were found between either FCB and BDP, or FCB and DSCG in either group.

Topics: Allergens; Asthma; Beclomethasone; Cromolyn Sodium; Drug Evaluation; Fluocortolone; Forced Expiratory Volume; Humans; Time Factors

A comparison was performed between inhalation of salbutamol as a powder aerosol or as a pressurized aerosol. Seven intrinsic asthmatics, well-trained in inhalation technique, were studied in an open randomized crossover comparison of the two different modes of administration. Five doses were inhaled of salbutamol from the pressurized aerosol, 0.1-2.4 mg, and five doses as a powder aerosol from a Rotahaler, 0.2-4.8 mg. The FEV1 dose-response curves were almost identical indicating bronchodilating equipotency between the two modes of administration. A preliminary report is given of the effects on morning cortisol of inhalation of beclomethasone dipropionate as a powder aerosol or as a pressurized aerosol in 10 healthy volunteers trained in inhalation technique. Morning cortisol decreased to the same degree after both modes of administration and the decrease was dose-dependent when beclomethasone dipropionate was given in the doses 200 micrograms, 500 micrograms and 1000 micrograms q.i.d. Thus, in patients with a good inhalation technique the powder aerosol does not seem to be better than the pressurized aerosol. We think, however, that it could be offered as an alternative to patients with poor inhalation technique.

Topics: Aerosols; Albuterol; Asthma; Beclomethasone; Humans; Powders; Pressure; Random Allocation; Respiratory Therapy

Twenty-nine patients treated with beclomethasone dipropionate (BDP) because of asthma were tapered off BDP stepwise at 3 weeks intervals in a single blind manner. Every day the patients recorded morning and evening peak expiratory flow, symptom scores for night and day and their consumption of medicine. Evening peak flow was the most sensitive variable to detect a deterioration in the asthmatic condition. In 7 patients no significant change in asthma symptoms occurred. The remaining 22 patients then participated in a randomized double-blind trial comparing their daily dose of BDP given as 4 divided doses or as 2 doses. No significant difference was found between these two regimens.

Topics: Adult; Aged; Asthma; Beclomethasone; Female; Humans; Male; Middle Aged; Respiratory Therapy

The efficacy and side-effects of a new corticosteroid aerosol, budesonide and beclomethasone dipropionate were assessed in 30 patients with chronic asthma in a double-blind cross-over study. Budesonide was administered, 200 micrograms twice daily, from a conventional pressurized aerosol with a tube spacer extension attached and beclomethasone was given via a conventional inhaler in the recommended four times daily dose of 100 micrograms, each treatment being administered for one month. No clinically significant differences were found between the two treatments and no significant side-effects were observed.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Pregnenediones

Steroid-dependent, chronic asthmatic patients with severe rhinitis or nasal polyps are often candidates for treatment with intranasal topical corticosteroids, such as flunisolide. The possibility of additive adrenal suppression, when flunisolide, beclomethasone and prednisone are given together, has not previously been studied. The need to asses the risk is suggested by reports of additive adrenal suppression when aerosol and oral steroids are used together to treat asthma, and by the demonstrably higher systemic availability of aerosol steroid given intranasally rather than via the lung. We performed a double-blind, placebo-controlled crossover assessment of the efficacy and safety of 3 weeks of intranasal flunisolide spray treatment (300 micrograms/day) in nineteen steroid-dependent chronic asthmatic subjects, who also had nasal polyps or severe rhinitis. During the study, their doses of prednisone and beclomethasone, used for asthma, were held stable. Morning serum cortisol levels and 24-hr urinary-free cortisol excretion were essentially the same after the placebo, and the flunisolide treatments. The intranasal flunisolide improved their nasal symptoms significantly (P less than 0.05). Local complications were negligible. Given conventional steroid doses like those used in this study, there appears to be no important risk to endogenous adrenal function from combining the use of intranasal, flunisolide spray with administration of other steroids by other routes, when this is deemed clinically necessary. If higher doses are used, the possibility of some additive adrenal suppressive effect cannot be excluded.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Drug Therapy, Combination; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Middle Aged; Nasal Polyps; Prednisone; Rhinitis, Allergic, Perennial

Sixty-seven asthmatic individuals treated with either beclomethasone diproprionate or flunisolide were sequentially evaluated for up to 32 months to determine the incidence of oropharyngeal candidiasis as well as laboratory parameters which might be predictive of this complication. Throat cultures and measurements of Candida antibody by immunodiffusion and radioimmunoassay were performed and compared over time and treatment groups. Unlike other studies, pre-treatment Candida precipitins did not predict increased risk for clinical thrush nor did quantitative determinations of Candida antibody. Those patients with positive cultures pre-trial, however, had a significantly higher incidence of clinical thrush than those with negative cultures (P less than 0.01). No significant changes occurred over time or between drugs for any of the parameters. Symptomatic thrush, however, was slightly more common in those patients treated with beclomethasone.

Topics: Adolescent; Adult; Aerosols; Aged; Antibodies, Fungal; Asthma; Beclomethasone; Binding Sites, Antibody; Candida; Candidiasis, Oral; Female; Fluocinolone Acetonide; Humans; Male; Middle Aged; Nystatin; Risk

Some patients with chronic asthma treated with beclomethasone aerosol (BA) derive significant symptom benefit, yet have persisting adrenal suppression due in part to their BA therapy. The daily dose of BA required is higher in patients with atopy. We therefore assessed the usefulness of ancillary treatment with cromolyn sodium (CS), a drug known to inhibit atopic asthma, to try to improve the balance of risk vs benefit in such patients. Thirty asthmatics, well controlled on high-dose BA (mean, 1,040 micrograms +/- 97 SE) but with morning cortisol levels averaging approximately 10 micrograms/dl, were allocated randomly to placebo or CS inhalant, used in addition to their regular BA and other asthma medications. After 4 wk, their BA dose was halved. Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows, and by spirograms and morning serum cortisol tests every 4 wk. Mean cortisol levels rose 27% after BA dose reduction (p less than 0.05) but asthma worsened. Risk-benefit assessments 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75%. The distributions of good, fair, and poor risk-benefit responses were the same in both CS and placebo-treated groups (p = 0.20). In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients, CS might prove useful, but in these adult chronic asthmatics with this particular therapeutic problem, there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen.

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Drug Combinations; Humans

We examined the value of maintenance theophylline at serum concentrations of 10 to 20 micrograms per milliliter in a placebo-controlled, randomized, double-blind trial of 33 children with steroid-dependent chronic asthma. Patients were free of all symptoms 63 +/- 6 per cent of the days (mean +/- S.E.M.) when taking theophylline as compared with 42 +/- 6 per cent when taking placebo (P < 0.01). Inhaled metaproterenol was required twice as often with placebo (P < 0.01), and additional daily corticosteroids were needed more than three times as often with placebo (P = 0.02). Daily peak flow measurements improved with theophylline (P < 0.01) as did monthly spirometric measurements and residual volume measured by plethysmography. Theophylline was associated with a 50 per cent increase in the number of patients able to complete an exercise test (P = 0.01) and with a smaller decrease in forced expiratory volume in one second among patients completing the exercise (P < 0.02). We conclude that maintenance bronchodilator therapy with theophylline can provide clinically important benefit for patients with chronic steroid-dependent asthma.

Topics: Adolescent; Adult; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Double-Blind Method; Forced Expiratory Flow Rates; Humans; Metaproterenol; Peak Expiratory Flow Rate; Physical Exertion; Placebos; Prednisone; Random Allocation; Spirometry; Theophylline

Sixty patients with fairly stable asthma of mild or moderate severity entered a multicentre, double-blind cross-over trial, comparing the efficacy of inhaled beclomethasone dipropionate preceded 10 minutes earlier by inhalation of salbutamol with that of beclomethasone followed 10 minutes later by salbutamol during two consecutive three-month periods. Patients received beclomethasone 100 microgram and salbutamol 200 microgram four times daily. Analysis of occurrence of exacerbations, usage of additional inhaled salbutamol, peak expiratory flow rate and symptom scores showed no evidence that regular beclomethasone was more effective when preceded by salbutamol rather than when followed by it.

Topics: Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged

Twenty patients with asthma controlled by oral inhalations of beclomethasone dipropionate (400 micrograms/day) were treated for concurrent rhinitis by the addition of flunisolide nasal solution (300 micrograms/day) and its placebo for three weeks each in a randomized, double-blind, crossover trial. Flunisolide produced a statistically significant benefit for each symptom parameter: sneezing (p = 0.013), runny nose (p = 0.027), stuffy nose (p = 0.005 and over-all severity (p = 0.005). More concomitant rhinitis medication was used during placebo treatment (p = 0.069). Seventy percent of the patients had "total" or "substantial" control of nasal symptoms with flunisolide vs. 45% with placebo (p less than 0.01). Eighty percent felt that flunisolide was either the only active drug or the more active (p less than 0.01). Three morning plasma cortisol determinations during the last week of each treatment period showed no drug-related effect. No nasal cultures were positive for Candida; the incidence of positive pharyngeal; cultures did not vary significantly. Adverse reactions consisted primarily of nasal burning and stinging; none was serious. In this group of twenty patients using inhalations of beclomethasone dipropionate for asthma, accompanying perennial rhinitis was substantially controlled by 300 micrograms of flunisolide nasal solution per day without significant additive effect on plasma cortisol levels or the incidence of overgrowth of Candida.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Candida albicans; Female; Fluocinolone Acetonide; Humans; Male; Middle Aged; Pharynx; Rhinitis, Allergic, Perennial

Because the simultaneous use of more than one form of topical corticosteroid involves higher cumulative doses and, therefore, more potential for absorption, this study was concerned primarily with effect on adrenal function. Seventeen adults whose asthma symptoms had been stable for at least three months on 100-400 microgram/day of beclomethasone dipropionate aerosol received flunisolide intranasal solution (200 microgram/day) combined with its intrabronchial form (1 mg/day) or with beclomethasone dipropionate bronchial aerosol (400 microgram/day). Utilizing a physician-blind, crossover design, each medication combination was administered for one month. Patient and physician evaluations revealed no significant differences in efficacy, adverse effects (complaints) or effect on adrenal function between the two combinations. Thus, the addition of intranasal flunisolide to intrabronchial flunisolide or beclomethasone did not appear to result in significant systemic absorption of corticosteroid above that which might have occurred as a result of the bronchial inhalation of corticosteroid medication alone during the pretrial period.

Topics: 11-Hydroxycorticosteroids; Administration, Intranasal; Adult; Aerosols; Asthma; Beclomethasone; Female; Fluocinolone Acetonide; Forced Expiratory Volume; Humans; Male; Middle Aged; Rhinitis, Allergic, Perennial; Vital Capacity

Topics: Adult; Aerosols; Asthma; Atropine; Beclomethasone; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Male; Middle Aged

A randomized multicentre trial was done to investigate the protective effects of ketotifen and disodium cromoglycate (DSCG) in the therapy of bronchial asthma. 236 patients with seasonal asthmatic symptoms were treated and controlled in the summer of 1978. Both drugs showed a significant improvement of the lung function and a marked reduction of asthmatic symptoms, cough and expectoration.

Topics: Adrenergic beta-Agonists; Asthma; Beclomethasone; Bronchitis; Clinical Trials as Topic; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Ketotifen; Piperidines; Random Allocation; Seasons; Spirometry; Theophylline; Thiophenes

An open, parallel comparison of flunisolide and beclomethasone dipropionate nasal sprays is described. Sixty patients entered the study of whom fifty-six completed the full 4 weeks' therapy. The dosage of flunisolide was two actuations (25 micrograms/actuation) into each nostril twice a day (total 200 micrograms). The dosage of beclomethasone dipropionate was one actuation (50 micrograms) in each nostril four times a day (total 400 micrograms). Both drugs produced statistically significant improvements compared with admission values in sneezing, stuffiness, runny nose, nose blowing and post-nasal drip. Both drug significantly decreased the interference by symptoms with routine life and sleep. At the end of the trial both treatment groups showed total or good control of symptoms in the majority of patients. No statistically significant difference was shown between the effects of the two drugs. Side-effects did not cause withdrawal from the trial in any patient and were mostly confined to minor headache and nose and throat complaints. In neither treatment group was there any evidence of adrenal suppression or growths of Candida from nasal swabs.

Topics: Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Physician-Patient Relations; Rhinitis, Allergic, Perennial; Skin Tests

Topics: Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Humans; Middle Aged

In a double-blind trial, beclomethasone dipropionate inhaled as a dry powder in doses of 200 micrograms three times a day was compared with the conventional aerosol of 100 micrograms three times a day, each for a period of 4 weeks. Neither the dry powder nor the aerosol showed any significant advantage over each other in terms of ventilatory function. Plasma cortisol levels were unaltered with the two medications in spite of the doubled dose of the corticosteroid powder. Choice of one or the other method of administration of medication depended on patient preference and the ease with which he could familiarize himself with either technique.

Topics: Administration, Intranasal; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Powders

Topics: Adult; Aerosols; Asthma; Beclomethasone; Bronchitis; Child; Clinical Trials as Topic; Double-Blind Method; Humans; Placebos; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal; Time Factors

Beclomethasone dipropionate inhaled as a dry powder in doses of 200 microgram four times a day was compared with the usual dose of 100 microgram four times a day from a pressurized aerosol in 65 patients with asthma who used pressurized aerosols correctly. Each treatment was given for an eight-week period. The dry powder did not show any clinically significant advantage over the aerosol in terms of ventilatory function as measured by FEV1 and the daily peak flow measurements during both treatments did not differ. The incidence of oral candidiasis was low and no other side-effects were encountered. It was concluded that beclomethasone dipropionate in dry powder form was as effective as aerosol in the treatment of asthma.

Topics: Administration, Oral; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Powders; Respiratory Function Tests

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Candidiasis; Candidiasis, Oral; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Nystatin; Respiratory Tract Infections; Time Factors; Voice Disorders

The efficiencies of two metered dose delivery systems designed for oral inhalation of glucocorticoids (triamcinolone acetonide and beclomethasone dipropionate) were compared in an open-labeled, randomized, crossover fashion in 18 asthmatic patients. Measurements were made of the mean amount of glucocorticoid released per actuation at the aerosol valve of each delivery system, the mean amount in a post-dose gargle and saliva specimen and the mean amount that remained in the oral adapter after use of each system. Retention in the oropharyngeal cavity was 7.3% and 40.3% of delivered dose for the triamcinolone acetonide and beclomethasone dipropionate systems (P < 0.001). The amount of glucocorticoid potentially available to the bronchial airways was 92.7% of the delivered dose for the triamcinolone acetonide and 59.7% for the beclomethasone dipropionate system.

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Triamcinolone Acetonide

Beclomethasone dipropionate (BDP) was used in a trial to assess the effectiveness of twice daily compared with four times daily dosage in the control of asthma. Prior to the introduction of BDP all but one of the patients were dependent on oral steroids in addition to other therapeutic regimes for adequate control of their asthma. A cross-over design was used with patients randomly allocated to either a twice daily or four times daily initial BDP regime. The trial continued for thirty-two weeks, with patients changing their dose regime at the end of each eight week period. Maintenance steroids were eliminated in all but two of the patients. According to all the criteria used in assessing control of asthma, there were no significant differences between the two regimes, indicating that both were equally effective. Compliance was better with the twice daily regime, and most patients preferred it.

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Child Development; Eczema; Female; Humans; Male; Middle Aged; Patient Compliance; Rhinitis, Allergic, Seasonal; Statistics as Topic; Steroids

Topics: Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Drug Evaluation; Humans; Tablets

Topics: Adrenal Cortex; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Cushing Syndrome; Depression, Chemical; Drug Antagonism; Drug Therapy, Combination; Humans; Prednisone; Stimulation, Chemical

Topics: Aspirin; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Sympathomimetics

14 children with severe asthma were studied for 2 months in a double-blind cross-over trial to compare the efficacy of beclomethasone dipropionate delivered as an aerosol and as a powder from a rotahaler. Inhalation via the aerosol was satisfactory in 13 patients, each of whom used the rotahaler correctly. Younger children preferred to use the rotahaler. Comparison of daily symptoms, twice daily peak expiratory flow rate (PEFR), and use of salbutamol during the 2 months of the trial showed that control of asthma was equally good, irrespective of the device used to deliver active beclomethasone.

Topics: Adolescent; Aerosols; Age Factors; Asthma; Attitude to Health; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Powders

A follow-up study to 52 weeks is reported on 95 corticosteroid-dependent asthmatics who took part in a double-blind, controlled trial of beclomethasone dipropionate for 28 weeks. During the 28 weeks two dosage schedules (800 microgram and 400 microgram daily) were compared with a placebo. If the corticosteroid tablet dosage had been at least halved and the clinical condition was satisfactory, the allocated regimen was continued 'blind' for the second period (29-52 weeks); 51 patients continued for this period, 46 on beclomethasone dipropionate. If progress was unsatisfactory, known beclomethasone dipropionate 800 microgram daily was substituted, the supervision remaining unchanged, the clinical supervisors remaining unaware which schedule had been received during the first 28 weeks. Nearly all the patients who at least halved their corticosteroid tablet dosage by 28 weeks continued to do well up to 52 weeks on the allocated regimen. When the placebo patients with unsatisfactory progress at 28 weeks were changed to 800 microgram beclomethasone dipropionate they showed a substantial improvement. Patients changed from 400 to 800 microgram showed little improvement on average. Approximately 30% of the whole group of patients failed to have their dosage of corticosteroid tablets, despite receiving 800 microgram beclomethasone dipropionate daily for six or more months. The cumulative incidence of 'oral candidiasis' (as defined for this report) in placebo patients changed at 28 weeks to 800 microgram beclomethasone dipropionate daily was 30% at 36 weeks and 43% at 52 weeks. Of eight patients increased from 400 microgram to 800 microgram daily, one had 'candidiasis' by 36 weeks and three by 52 weeks. Oral candidiasis was often asymptomatic and never led to the discontinuation of the corticosteroid aerosol, although the dosage was reduced in nine of the 30 who received 800 microgram beclomethasone dipropionate during the first 28 weeks. The incidence of bacterial infections in patients on beclomethasone dipropionate was similar to that of the placebo group and systematic laboratory investigations revealed no increase in the rate of isolation of potential pathogens.

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Candidiasis, Oral; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Placebos; Sputum

Fourteen children with perennial asthma previously treated with beclomethasone dipropionate were studied for four months in a crossover trial to compare the efficacy of choline theophyllinate and beclomethasone dipropionate aerosol in the control of their symptoms. Assessments were made using twice daily peak flow measurements, together with daily records of symptom scores and use of extra salbutamol. Beclomethasone and oral choline theophyllinate together improved control of asthma in comparison with beclomethasone alone. Reduction of the dose of beclomethasone from 400 microgram/day caused worsening of asthma. Oral choline theophyllinate did not prevent this deterioration and therefore cannot replace beclomethasone for the long-term treatment of such asthmatic patients.

Topics: Administration, Oral; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Male; Theophylline

A double-blind cross-over trial was carried out to compare the effect of identical placebo with that of salbutamol inhalers used 30 min before inhalation of 100 microgram of beclomethasone dipropionate (B.D.P.) in 18 chronic asthmatics over two consecutive 4-week periods. The salbutamol and B.D.P. combination resulted in a significant improvement in the peak expiratory flow-rate and F.E.V.1, significantly less use of the rescue inhaler, and better control.

Topics: Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Bronchi; Chronic Disease; Circadian Rhythm; Clinical Trials as Topic; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos

Topics: Adult; Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Humans; Hydrocortisone; Time Factors

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Topics: Administration, Oral; Adolescent; Adrenal Glands; Adult; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Lung; Male; Pituitary Gland; Pituitary-Adrenal Function Tests; Prednisone

In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Powders; Respiratory Function Tests; Respiratory Therapy

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.

Topics: Administration, Oral; Adolescent; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Desoxycorticosterone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hydrocortisone; Metyrapone; Pituitary-Adrenal System; Prednisone

The efficacy of beclomethasone diproprionate aerosal (BDA) was studied in 27 steroid-dependent asthmatic children. In the double-blind portion of the study BDA was found to be superior to placebo. The benefits of BDA therapy were sustained through the two-year, open-label portion of the study. Adverse effects were few and minor. Transfer from oral corticosteroid therapy to BDA was carried out uneventfully and was not associated with untoward effects.

Topics: Adolescent; Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Female; Humans; Male

The average prednisone dosage of 54 corticosteroid-dependent asthmatics was computed for one year prior to initiation of beclomethasone dipropionate. This was compared to the average prednisone dosage after nine months on the beclomethasone with progressive tapering of prednisone to either dose compatible with control of asthma or discontinuation. Beclomethasone was found clinically useful in the great majority of these patients because it permitted a significant decrease in dosage of prednisone, a change from daily to alternate-day prednisone, or discontinuation of prednisone after cautious tapering. The first two advantages were most evident in those asthmatics who initially required higher doses of oral steroids while the latter was evident in those requiring lower doses. Those patients whose prednisone dosage does not appear to be beneficially affected by the use of beclomethasone should be suspect as to adherence to proper medical dosage schedule.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Patient Compliance; Prednisone; Retrospective Studies; Time Factors

A clinical comparison of conventional aerosol administration of beclomethasone dipropionate and insufflation as a powder using the "Rotahaler" device in four doses of 100 microgram each was made in thirty-seven cases. Each treatment was given for 4 weeks, the order being randomized. Symptom records, twice daily peak flow readings and records of bronchodilator and steroid dosage showed the powder to be as effective as the aerosol. In the physician's opinion the powder was preferable to the aerosol in some cases.

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Female; Humans; Male; Peak Expiratory Flow Rate; Powders

Topics: Administration, Intranasal; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Rhinitis, Allergic, Seasonal

In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Candidiasis, Oral; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eosinophils; Female; Humans; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Prednisone

The efficacy of inhaled beclomethasone dipropionate has been examined in 44 steroid-dependent asthmatics observed for 9 months to 2 years. A 3-month double-blind trial found that subjects treated with beclomethasone had a significant diminution in symptoms, were able to reduce their use of medication, and had improved maximum expiratory flow rates. Approximately one half were able to discontinue the use of oral prednisone within 9 months after starting beclomethasone, and a further one third reduced their dose by at least 50%. No characteristics could be defined to predict responsiveness to beclomethasone. The effectiveness of beclomethasone was sustained for as long as 2 years and was not associated with any abnormal urine, blood, or serum values or chest X-ray findings. Candidiasis of the palate appeared in approximately one third of the subjects and was usually transient. The chronic use of beclomethasone did not result in endocrine suppression.

Topics: Administration, Oral; Aerosols; Anti-Bacterial Agents; Asthma; Beclomethasone; Candidiasis; Clinical Trials as Topic; Forced Expiratory Volume; Humans; Placebos; Prednisone; Substance-Related Disorders; Vital Capacity

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Cough; Humans; Spasm

Topics: 17-Hydroxycorticosteroids; Adolescent; Adrenal Cortex Hormones; Adult; Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Dexamethasone; Dexamethasone Isonicotinate; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Candida; Child; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Pharynx; Pituitary-Adrenal Function Tests; Placebos

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.

Topics: Administration, Oral; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Humans; Hydrocortisone; Hypothalamus; Pituitary Gland; Prednisone; Substance Withdrawal Syndrome

1. In 48 patients with chronic asthma who had been receiving treatment with beclomethasone dipropionate aerosol (BDA) at a daily dose of 400 microgram for several years, observations were made on the effect of increasing the dose to 800 microgram daily for 6 months. 2. There was subjective improvement in 37 of the 48 patients, but the only objective evidence of improvement was a slight reduction in airways resistance. 3. The higher dose of BDA did not produce impairment of pituitary-adrenal function or an increase in the incidence of oropharyngeal candidiasis.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Time Factors

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aerosols; Aged; Aspergillosis; Asthma; Beclomethasone; Candidiasis; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Pregnancy; Seasons; Substance-Related Disorders; Time Factors

1. Beclomethasone dipropionate aerosol has been shown to be a highly effective treatment for asthma in childhood, with virtual absence of side effects at this age. 2. When treatment is unsuccessful, this is usually due to failure to take it correctly and regularly. 3. A good response is usually associated with an improvement in ventilatory function and a marked increase in growth velocity.

Topics: Adolescent; Adrenal Cortex Hormones; Aerosols; Asia; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Ireland; Male; Social Class; Time Factors; United Kingdom; West Indies

Topics: Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Follow-Up Studies; Humans

1. The findings of an open trial of beclomethasone dipropionate aerosol (BDA), carried out in 1972 in the author's general practice, are discussed in the light of subsequent, more extensive experience of its use of BDA. 2. An important reason why BDA may be unsuccessful in controlling asthma, and may give rise to various problems, is that patients are often given an inadequate explanation of the purpose and proper use of this treatment.

Topics: Adrenal Cortex Hormones; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Family Practice; Female; Humans; Male; Middle Aged; Time Factors

1. Five years' experience in the use of beclomethasone dipropionate aerosol (BDA) in the treatment of 315 patients with upper respiratory tract allergy is reviewed. 2. A total of 223 patients with perennial rhinitis was treated. In 23, where the nasal allergy had recurred after oral corticosteroid therapy for asthma was withdrawn, BDA was effective in 69% of cases. A similar success rate (68%) was recorded in 169 patients suffering from perennial allergic rhinitis alone, but a satisfactory response was observed in only 45% of 31 patients with nasal polypi. 3. In 92 patients with seasonal allergic rhinitis freedom from symptoms was achieved in 80%. 4. A total of approximately 534 patient-years of treatment has been recorded without any evidence of side-effects either clinically or on nasal biopsy.

Topics: Aerosols; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Humans; Rhinitis; Seasons

Topics: Administration, Oral; Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Respiratory Therapy; Time Factors

Topics: Asthma; Beclomethasone; Biopsy; Bronchi; Bronchoscopy; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Follow-Up Studies; Humans; Mucous Membrane; Time Factors

Topics: Aerosols; Asthma; Beclomethasone; Bronchial Diseases; Bronchoscopy; Humans; Time Factors

Beclomethasone dipropionate aerosol (BDA), 50 mug four times daily sprayed into each nostril, was compared with placebo in a double-blind crossover trial in 26 patients with perennial rhinitis. Patients received BDA for 3 weeks and placebo for 3 weeks; the order of administration was randomized. Response was assessed with daily symptom score cards and twice weekly measurements of nasal airway inspiratory resistance at a standard flow rate of 0.4 L/sec. Symptom score and nasal resistance during BDA treatment were significantly lower than those duirng placebo treatment (p less than 0.02 and p less than 0.05, respectively) in the third week. Eighteen of the patients expressed a preference for BDA, 6 for placebo, and 2 for neither (p less than 0.05). Acceptable symptomatic improvement (moderate or marked) was achieved by 54%. Mild side effects were noted by 5 patients; these included nasal irritation and bleeding in 2, aerosol-induced sneezing in 2, and headache in 1. These side effects occurred in 3 patients who used BDA, 1 who used placebo, and 1 who used both. After a 6-mo follow-up period, in which the dose of BDA was adjusted and concurrent initial oral prednisone was administered to patients who were treatment failures, 73% of the patients obtained moderate or marked symptomatic improvement. No further side effects were noted during this time. Results in those in whom a possible allergic component could be identified were not different from those of the whole group. We conclude that BDA is a useful addition to the therapy of perennial rhinitis.

Topics: Administration, Intranasal; Aerosols; Airway Resistance; Asthma; Beclomethasone; Dust; Female; Humans; Immunoglobulin E; Male; Mites; Nasal Polyps; Rhinitis, Allergic, Seasonal

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Drug Evaluation; Female; Humans; Male; Middle Aged

Forty-two perennial asthmatic children were selected for a 12-wk study using beclomethasone dipropionate. The groups included 21 steroid-dependent children (Group I) and 21 patients (Group II) whose disease was of sufficient severity that corticosteroid therapy was contemplated. All children received the drug in a dose of 100 mug 4 times daily. During the study, oral prednisone was withdrawn from the steroid-dependent children while other therapy was essentially unchanged. Group II children underwent a double-blind trial, receiving beclomethasone for 6 wk and placebo for 6 wk. Objective assessment of adrenal and pulmonary function was obtained at regular intervals. For the latter, total lung capacity and its subdivisions, airways resistance, maximum expiratory flow volume, and oxygen tension, were measured in both groups. In Group II static elastic recoil was measured also. For most tests the results were statistically significant. In both groups, 18 of 21 patients demonstrated an excellent clinical response, no evidence of adrenal suppression, and improvement in pulmonary function. Forty of 42 patients were followed for another 12 wk, and 19 of each group did well. After 20-24 wk of therapy, 16% of patients harbored monilia in their oropharynx, and 1 patient had clinical monilial stomatitis. Within the limits of the time of the study, beclomethasone dipropionate appeared to provide adequate clinical control in many chronic, severe, steroid-dependent and nonsteroid-dependent asthmatic children.

Topics: 17-Ketosteroids; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Candidiasis, Oral; Child; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Respiratory Function Tests

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Betamethasone; Clinical Trials as Topic; Humans; Prednisone

In a double-blind, randomized study, 93 corticosteroid-independent patients with chronic bronchial asthma were treated with either beclomethasone dipropionate aerosol at 400 mug per day of its vehicle for 4 wk to determine and compare the effectiveness and safety of the preparations. Evaluations made before, at weekly intervals during, and 1 wk after treatment indicated that beclomethasone dipropionate aerosol was superior to its vehicle is improving FVC, FEV1, FEF25%--75%, and clinical signs and symptoms, and in the overall evaluations by both the investigators and the patients. Plasma cortisol levels measured at the end of the second and fourth weeks were not substantially different from those before treatment in either group. No significant side effects or abnormalities in laboratory results were noted.

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Methylprednisolone; Middle Aged; Respiratory Function Tests

Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

Topics: Adolescent; Adrenal Cortex Function Tests; Aerosols; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Cosyntropin; Female; Humans; Male; Methylprednisolone; Placebos; Rhinitis, Allergic, Seasonal

The theraprutic efficacy of inhaled beclomethasone dipropionate and inhaled betamethasone valerate in chronic asthma has been studied in 14 treatment centres in 158 patients who had previously been taking prednisone tablets regularly. Doses of 400 mug daily of beclomethasone dipropionate and a dose of 800 mug daily of betamethasone valerate allowed approximately 80% of patients to discontinue prednisone initially and 60% to remain off daily prednisone for 24 weeks. A mean reduction in daily prednisone dose of 8 mg was achieved by patients inhaling corticosteroids whilst placebo inhaler permitted a 5 mg reduction. The three inhaled corticosteroid preparations were equally effective in facilitating prednisone reduction and provided equally good control of asthma, alone or as an ancillary to prednisone. The higher dose of beclomethasone dipropionate was superior to the lower in permitting more patients to remain off daily prednisone for the period of the trial. Although 82% of patients recovered a normal adrenal response to tetracosactrin 24 weeks after prednisone was discontinued and inhaled corticosteroids subsituted, 18% still showed some suppression of adrenal function. There was no significant difference between the treatment groups in this.

Topics: Aerosols; Asthma; Beclomethasone; Betamethasone; Betamethasone Valerate; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Placebos; Prednisone; Substance Withdrawal Syndrome

In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Hydrocortisone; Lung Volume Measurements; Male; Methylprednisolone; Middle Aged; Prednisolone; Prednisone

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Methylprednisolone; Prednisolone; Prednisone

Beclomethasone dipropionate was found to be effective in reducing symptoms of asthma in children. There was no measurable influence on pulmonary function. An 18-month follow-up did not show untoward side effects on adrenal function, growth, serum electrolytes, and hepatic and renal functions with a dose of 100 mug three times daily. The treatment predisposes to the colonization with Candida albicans in the oropharynx.

Topics: Adrenal Cortex Function Tests; Asthma; Beclomethasone; Body Height; Body Weight; Child; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Respiratory Function Tests

A single-blind crossover trial comparing beclomethasone dipropionate by inhalation with prednisolone by mouth in the treatment of asthmatic children over a period of 10 months is reported. Fourteen children aged between nine and 16 years entered the trial. All had severe chronic asthma requiring maintenance oral prednisolone therapy in doses ranging from 2 to 7-5 mg/day. Beclomethasone dipropionate given by inhalation in a dose of 400 mug/day was found to be a satisfactory alternative to prednisolone by mouth for controlling the symptoms of asthma. During the course of this trial, three of the children died suddenly during acute exacerbations of asthma. All three had evidence of extensive inflammation of the tracheobronchial tree.

Topics: Adolescent; Aerosols; Asthma; Autopsy; Beclomethasone; Bronchi; Child; Clinical Trials as Topic; Death, Sudden; Humans; Placebos; Prednisolone; Trachea

Topics: Aerosols; Asthma; Beclomethasone; Bronchitis; Candida albicans; Child; Female; Humans; Male; Pharynx; Respiratory Therapy

Topics: Adult; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Middle Aged

Topics: Adolescent; Age Factors; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Prednisolone

Topics: Adrenal Cortex Hormones; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Body Weight; Bronchitis; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Substance-Related Disorders

Topics: Adolescent; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Cromolyn Sodium; Drug Combinations; Female; Humans; Male; Methylprednisolone; Placebos

Topics: Adult; Aerosol Propellants; Aerosols; Asthma; Beclomethasone; Bronchi; Chlorofluorocarbons, Methane; Forced Expiratory Volume; Humans; Hydrocarbons, Halogenated; Middle Aged

Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adrenal Cortex Function Tests; Adrenal Glands; Aerosols; Asthma; Beclomethasone; Betamethasone; Clinical Trials as Topic; Cosyntropin; Cromolyn Sodium; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Placebos; Prednisone

Topics: Adolescent; Adult; Allergens; Animals; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Cromolyn Sodium; Desensitization, Immunologic; Drug Hypersensitivity; Female; Histamine Release; Humans; Male; Middle Aged; Physical Exertion; Rats; Rhinitis, Allergic, Seasonal; Stimulation, Chemical

Beclomethasone dipropionate is a topically active corticosteroid used as an adjuvant in the control of chronic asthma when given by inhalation as an aerosol. It is not intended for treatment of acute attacks. It appears that the main difference between beclomethasone dipropionate and other corticosteroids previously used by inhalation is its high topical activity together with a lower systemic activity due to metabolic inactivation of the swallowed portion of the dose. Clinical experience has shown that at doses of 200 to 600mug daily, beclomethasone dipropionate inhaler is preferable to oral corticosteroids, because of lack of side-effects, when adult patients and children who are inadequately controlled by full doses of sodium cromoglycate and bronchodilators, are first considered to need maintenance corticosteroids. Inhaled beclomethasone dipropionate can allow a worthwhile reduction in maintenance doses of systemic corticosteroids in many patients already receiving these drugs and can replace systemic steroids entirely in some patients, particularly when their initial dose of steroids is less than 10mg daily of prednisone or its equivalent. Substitution should be attempted when the patient's asthma is well controlled on their usual doses of systemic steroids and full doses of other adjuvant therapy. Withdrawal of systemic corticosteroids should be performed slowly and carefully. Because recovery from impaired adrenocortical function caused by prolonged systemic steroid therapy is usually slow, special care is necessary for 9 to 12 months after transfer to beclomethasone dipropionate aerosol until the hypothalamo-pituitary-adrenal axis has sufficiently recovered to cope with emergencies such as trauma, surgery, severe infections or an acute attack of asthma. It is essential that additional therapy including high doses of systemic corticosteroids be used immediately to control any acute exacerbation of asthma which occurs during maintenance therapy with beclomethasone dipropionate aerosol. Tests of adrenal function suggest that beclomethasone dipropionate at dosages of 400 to 800 mug daily has little or no adverse effect. The most common side-effect associated with the continuous use of beclomethasone dipropionate inhaler has been oropharyngeal candidiasis, which appears to be dose-related and more common in women than in men. Systemic steroid withdrawal effects, like being generally unwell, and exacerbation of underlying allergic diseases such as aller

Topics: 17-Ketosteroids; Administration, Oral; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Drug Evaluation; Forced Expiratory Volume; Half-Life; Humans; Hydrocortisone; Kinetics; Methylprednisolone; Middle Aged; Substance-Related Disorders

Topics: Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Forced Expiratory Volume; Humans; Male; Methylprednisolone; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Female; Humans; Infant; Infant, Newborn; Lung Diseases, Obstructive; Male; Methylprednisolone; Middle Aged; Prednisone; Substance-Related Disorders

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Cromolyn Sodium; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Methylprednisolone

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Cromolyn Sodium; Female; Follow-Up Studies; Humans; Male; Methylprednisolone; Middle Aged; Steroids; Substance-Related Disorders

Topics: Administration, Oral; Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Betamethasone; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Particle Size; Propionates; Triamcinolone; Valerates

Beclomethasone dipropionate aerosol therapy can replace or diminish systemic corticosteroid therapy in the majority of asthmatics. In a clinical trial of 41 patients with perennial asthma, the 10 who had not required long-term corticosteroid therapy improved symptomatically and in pulmonary function. Of the 31 who had required prolonged systemic corticosteroid therapy 12 were able to discontinue oral prednisone therapy, 15 were able to decrease the maintenance dose of prednisone and only 4 were unable to decrease the dose; all maintained satisfactory lung function and some showed improvement. Discontinuation of systemic corticosteroid therapy was accomplished more readily in patients whose daily maintenance dose was less than 15 mg and who had been taking the drug for less than 3 years. Side effects consisted of a "dry throat" in seven patients, two of whom had throat infections with Candida albicans. Recurrence of rhinitis after discontinuation or reduction of systemic corticosteroid therapy was noted in 11 patients.

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Clinical Trials as Topic; Cough; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Prednisone; Respiratory Function Tests; Sputum

Topics: Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Humans; Hydrocortisone; Methylprednisolone

Topics: Administration, Intranasal; Administration, Oral; Asthma; Beclomethasone; Betamethasone; Betamethasone Valerate; Clinical Trials as Topic; Humans; Methylprednisolone; Prednisone

Topics: Adolescent; Adult; Aerosol Propellants; Asthma; Beclomethasone; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Leukocytosis; Male; Methylprednisolone; Middle Aged

Topics: Adolescent; Adrenal Cortex Hormones; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone

Topics: Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Growth Hormone; Humans; Hydrocortisone; Methylprednisolone

Topics: Asthma; Beclomethasone; Bronchi; Clinical Trials as Topic; Humans; Methylprednisolone; Mucous Membrane

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Methylprednisolone; Prednisolone

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Spirometry

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Cough; Female; Humans; Male; Methylprednisolone; Middle Aged; Rhinitis; Rhinitis, Allergic, Seasonal

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Methylprednisolone; Middle Aged; Pregnancy; Rhinitis, Allergic, Seasonal; Steroids; Substance-Related Disorders

Topics: Adolescent; Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Methylprednisolone; Middle Aged; Respiratory Function Tests; Steroids

Topics: Aerosols; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Hydrocortisone; Methylprednisolone; Prednisolone; Respiratory Function Tests

Topics: Aerosols; Asthma; Beclomethasone; Bronchitis; Chronic Disease; Clinical Trials as Topic; Humans; Methylprednisolone; Middle Aged; Prednisone

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Methylprednisolone; Middle Aged

Topics: Adolescent; Adrenal Glands; Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged

Topics: Adult; Aerosols; Aged; Asthma; Beclomethasone; Clinical Trials as Topic; Humans; Methylprednisolone; Middle Aged

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aerosols; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Humans; Methylprednisolone; Pituitary-Adrenal Function Tests; Substance-Related Disorders

Topics: Airway Resistance; Asthma; Beclomethasone; Child; Humans; Methylprednisolone

1) A 4-week single-blind study is reported which compares the responses of 10 matched pairs of adult asthmatic patients to Beclomethasone Dipropionate and Dexamethasone Isonicotinate aerosols, each at 12 metered-doses per day. 2) Therapeutic efficacy was evaluated by measurement of pulmonary function (PEFR) and by a physician's "overall evaluation" scale. 3) Side-effects related to systemic absorption were evaluated by A.M. blood cortisol levels and total eosinophil counts. 4) At the doses studied, Beclomethasone Dipropionate produced both no side-effects and a significant favourable clinical response, while Dexamethasone Isonicotinate produced significant side-effects and a lesser clinical response.

Topics: Adult; Aerosols; Asthma; Beclomethasone; Dexamethasone; Dexamethasone Isonicotinate; Eosinophils; Female; Humans; Hydrocortisone; Leukocyte Count; Male; Methylprednisolone; Middle Aged

Topics: Administration, Oral; Administration, Topical; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Candidiasis; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Methylprednisolone; Mouth Diseases; Mouth Mucosa; Nystatin; Pharyngeal Diseases; Placebos; Prednisone; Propionates

Topics: 17-Ketosteroids; Administration, Topical; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Blood Pressure; Body Weight; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Hydroxysteroids; Lung; Male; Middle Aged; Spirometry; Steroids; Substance-Related Disorders

Topics: Administration, Topical; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Child; Child, Preschool; Clinical Trials as Topic; Eczema; Female; Growth; Humans; Hydrocortisone; Male; Prednisone; Rhinitis; Rhinitis, Allergic, Seasonal; Time Factors

Topics: Aerosols; Airway Obstruction; Anti-Bacterial Agents; Asthma; Bacteria; Bacterial Infections; Beclomethasone; Carbenicillin; Child; Clinical Trials as Topic; Colistin; Corticosterone; Dexamethasone; Gentamicins; Humans; Hydrocortisone; Kanamycin; Lung Diseases, Fungal; Placebos; Polymyxins; Respiratory Therapy; Triamcinolone Acetonide

Topics: Adolescent; Adult; Asthma; Beclomethasone; Betamethasone; Clinical Trials as Topic; Cyclic AMP; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Placebos; Prednisolone; Respiration; Respiratory Therapy; Sputum; Time Factors

Topics: Adrenal Glands; Asthma; Beclomethasone; Betamethasone; Betamethasone Valerate; Depression, Chemical; Dexamethasone; Dexamethasone Isonicotinate; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Hypothalamus; Male; Methylprednisolone; Pituitary Gland

Betamethasone valerate aerosol is a new compound for the treatment of asthma. Its clinical effectiveness was established in a double-blind cross-over trial in non-steroid-dependent asthmatic patients. At a dosage of 400 to 800 mug/day for three months there was no evidence of suppression of hypothalamic-pituitary-adrenal function, as assessed by tetracosactrin and insulin stress tests.A 12-month follow-up study of 120 patients using steroid aerosols (betamethasone valerate or beclomethasone dipropionate) indicated that tolerance does not develop and that a daily maintenance dose of 200 mug/day was adequate in most patients. Temporary lack of response was observed during episodes of sputum production or of heavy exposure to antigen.There were no observed side effects other than fungal infections of the respiratory tract. However, the incidence of candidiasis of the pharynx (13%) and particularly of the larynx (5%) in apparently immunologically normal patients was disturbing. These infections were not seen in patients taking 200 mug/day. Though there is yet no evidence that fungal infections associated with steroid aerosols may penetrate the trachea and bronchi the possibility of this indicates that caution should be exercised in their use, particularly in long-term high dosage.

Topics: Adolescent; Adrenal Glands; Adult; Aerosols; Asthma; Beclomethasone; Betamethasone; Blood Glucose; Candidiasis, Oral; Clinical Trials as Topic; Drug Tolerance; Female; Follow-Up Studies; Humans; Hypersensitivity, Delayed; Hypothalamus; Insulin; Kidney Function Tests; Laryngeal Diseases; Lymphocyte Activation; Male; Middle Aged; Pharyngeal Diseases; Pituitary Gland; Placebos; Pulmonary Ventilation

The bronchodilator and cardiac effects produced by aerosols of 0.5% salbutamol and 0.5% and 1% rimiterol administered for three minutes in 40% oxygen by intermittent positive-pressure ventilation (I.P.P.V.) were compared in 15 asthmatic patients. Salbutamol and both the concentrations of rimiterol were equipotent in peak bronchodilator effect, but salbutamol had a significantly longer duration of bronchodilator action. There was significantly less increase in heart rate after rimiterol than after salbutamol. Aerosols of 0.5% rimiterol, 0.5% salbutamol, and saline were administered by I.P.P.V. to 10 normal volunteers. There was no difference between the mean heart rates after 0.5% rimiterol and saline but a highly significant increase in mean heart rate was observed after 0.5% salbutamol. It was concluded that 0.5% rimiterol was an effective short-acting bronchodilator drug with little or no cardiac beta(1)-adrenergic activity when administered for three minutes by I.P.P.V. in 40% oxygen.

Topics: Adult; Aerosols; Aged; Albuterol; Asthma; Beclomethasone; Bronchodilator Agents; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Positive-Pressure Respiration; Prednisolone; Spirometry; Sympathomimetics; Time Factors

Topics: 17-Hydroxycorticosteroids; Administration, Topical; Adolescent; Adult; Aerosols; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Methylprednisolone; Middle Aged; Placebos; Prednisone; Spirometry

Topics: Administration, Topical; Aerosols; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Glucocorticoids; Humans; Methylprednisolone; Placebos; Spirometry; Vital Capacity

A survey of 936 patients attending a respiratory diseases unit outpatient department was performed to assess the incidence of oropharyngeal candidiasis in patients inhaling beclomethasone dipropionate in daily doses of 400 mug or less. Throat swabs from 209 (41%) patients treated with beclomethasone were positive on culture for yeasts compared with positive swabs from 77 (27.2%) patients not receiving corticosteroid therapy either orally or by inhalation. Clinical oropharyngeal thrush, confirmed by culture, was detected in 28 (5.5%) patients inhaling beclomethasone, one (0.7%) patient receiving treatment with oral prednisolone, and two (0.7%) patients not being treated with corticosteroids.

Topics: Administration, Oral; Administration, Topical; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Candida; Candida albicans; Candidiasis; Candidiasis, Oral; Clinical Trials as Topic; Glucocorticoids; Humans; Pharyngeal Diseases; Pharynx; Prednisolone

Topics: Administration, Oral; Administration, Topical; Adrenal Insufficiency; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Glucocorticoids; Humans; Pharyngitis; Placebos; Prednisone; Respiratory Function Tests; Respiratory Tract Infections; Rhinitis, Allergic, Seasonal; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Administration, Topical; Adult; Aerosols; Aged; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Isoproterenol; Male; Middle Aged; Placebos; Prednisolone

Topics: Administration, Topical; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Drug Evaluation; Eosinophils; Female; Humans; Hydrocortisone; Leukocyte Count; Male; Middle Aged; Placebos; Respiration; Spirometry; Time Factors

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Beclomethasone; Betamethasone Valerate; Child; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged; Placebos; Substance Withdrawal Syndrome

Topics: Adolescent; Aerosols; Aged; Asthma; Beclomethasone; Betamethasone; Betamethasone Valerate; Clinical Trials as Topic; Female; Humans; Male; Methylprednisolone; Middle Aged

Topics: Administration, Oral; Adolescent; Adult; Aerosols; Asthma; Beclomethasone; Child; Child, Preschool; Exercise Test; Female; Glucocorticoids; Humans; Male; Physical Exertion; Placebos; Prednisone; Pulmonary Ventilation; Time Factors

Topics: Administration, Topical; Adult; Aerosols; Aged; Airway Obstruction; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Clinical Trials as Topic; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Middle Aged; Placebos; Spirometry; Time Factors

Thirty-one chronic perennial asthmatics aged from 2(1/2) to 16 years were treated with beclomethasone dipropionate pressurized aerosols for up to 20 months. Of these, 16 patients dependent on oral corticosteroid or corticotrophin for up to 11 years were successfully transferred to this treatment, with one exception. Steroid withdrawal symptoms were slight. Loss of weight, disappearance of Cushingoid features, and resumption of growth indicated lack of systemic side effects. Fifteen others inadequately controlled on bronchodilators or disodium cromoglycate, were also effectively treated, and no clinical evidence of adrenal suppression was noted.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Weight; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Spirometry

Topics: Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Clinical Trials as Topic; Eczema; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Recurrence; Rhinitis, Allergic, Seasonal; Spirometry

Topics: Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aerosols; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Cromolyn Sodium; Female; Humans; Hydrocortisone; Male; Methylprednisolone; Peptides; Prednisone; Spirometry

In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P <0.01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn.Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn.

Topics: Administration, Oral; Administration, Topical; Adrenocorticotropic Hormone; Aerosols; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Glucocorticoids; Humans; Methylprednisolone; Pituitary-Adrenal Function Tests; Placebos; Prednisolone

Topics: Administration, Topical; Adolescent; Adrenal Insufficiency; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Beclomethasone; Clinical Trials as Topic; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Clinical Trials as Topic; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Middle Aged; Placebos; Pulmonary Ventilation; Respiratory Therapy; Spirometry

Topics: Administration, Topical; Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Clinical Trials as Topic; Evaluation Studies as Topic; Female; Glucocorticoids; Humans; Male; Methylprednisolone; Respiratory Therapy; Time Factors

The real-world effectiveness and tolerability of an extrafine fixed dose beclomethasone/formoterol (BDP/FF) treatment of patients with partially or non-controlled asthma was evaluated in five non-interventional studies (NISs) from Austria.. Asthma patients enrolled in these five NISs were treated with beclomethasone/formoterol (Foster® or Foster® Nexthaler®) as maintenance and reliever over 12 weeks. Asthma control, lung function and symptom scores were assessed at baseline, after 4-8 weeks and at the end of the investigations in week 12. In addition, tolerability and handling of the devices were evaluated by questionnaires.. This combined analysis of five non-interventional studies confirms the effectiveness and tolerability of the extrafine fixed-dose BDP/FF combination (Foster® and Foster® Nexthaler®) in a heterogenous patient population suffering from partially or non-controlled asthma. Therapy was associated with a high patient satisfaction and the absence of serious adverse reactions.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Austria; Beclomethasone; Drug Combinations; Female; Formoterol Fumarate; Humans; Male; Treatment Outcome

This study aims to assess the effects of varying an ethanol co-solvent on the deposition of drug particles in severe asthmatic subjects with distinct airway structures and lung functions using computational fluid dynamics. The subjects were selected from two quantitative computed tomography imaging-based severe asthmatic clusters, differentiated by airway constriction in the left lower lobe. Drug aerosols were assumed to be generated from a pressurized metered-dose inhaler (MDI). The aerosolized droplet sizes were varied by increasing the ethanol co-solvent concentration in the MDI solution. The MDI formulation consists of 1,1,2,2-tetrafluoroethane (HFA-134a), ethanol, and beclomethasone dipropionate (BDP) as the active pharmaceutical ingredient. Since HFA-134a and ethanol are volatile, both substances evaporate rapidly under ambient conditions and trigger condensation of water vapor, increasing the size of aerosols that are predominantly composed of water and BDP. The average deposition fraction in intra-thoracic airways for severe asthmatic subjects with (or without) airway constriction increased from 37%±12 to 53.2%±9.4 (or from 20.7%± 4.6 to 34.7%±6.6) when the ethanol concentration was increased from 1 to 10%wt/wt. However, when the ethanol concentration was further increased from 10 to 20%wt/wt, the deposition fraction decreased. This indicates the importance of selecting appropriate co-solvent amounts during drug formulation development for the treatment of patients with narrowed airway disease. For severe asthmatic subjects with airway narrowing, the inhaled aerosol may benefit from a low hygroscopic effect by reducing ethanol concentration to penetrate the peripheral region effectively. These results could potentially inform the selection of co-solvent amounts for inhalation therapies in a cluster-specific manner.

Topics: Administration, Inhalation; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Beclomethasone; Ethanol; Humans; Hydrocarbons, Fluorinated; Respiratory Aerosols and Droplets; Solvents

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Drug Combinations; Formoterol Fumarate; Glycopyrrolate; Humans; Middle Aged; Young Adult

Exercise-induced bronchoconstriction (EIB) is a frequent and highly specific symptom of childhood asthma. Inhaled corticosteroids (ICS) are the mainstay of controller therapy for EIB and asthma; however, a proportion of asthmatic children and adolescents is less responsive to ICS. We hypothesized that a single dose response to ICS could function as a predictor for individual long-term efficacy of ICS.. To assess the predictive value of the bronchoprotective effect of a single-dose beclomethasone dipropionate (BDP) against EIB for the bronchoprotective effect of 4 weeks of treatment, using an exercise challenge test (ECT).. Thirty-two steroid-naïve children and adolescents aged 6 to 18 years with EIB were included in this prospective cohort study. They performed an ECT at baseline, after a single-dose BDP (200µg) and after 4 weeks of BDP treatment (100 µg twice daily) to assess EIB severity.. The response to a single-dose BDP on exercise-induced fall in FEV1 showed a significant correlation with the response on exercise-induced fall in FEV1 after 4 weeks of BDP treatment (r = .38, p = .004). A reduction in post-exercise fall in FEV1 of more than 8% after a single-dose BDP could predict BDP efficacy against EIB after 4 weeks of treatment with a positive predictive value of 100% (CI: 86.1-100%) and a negative predictive value of 29.4% (CI: 11.7%-53.7%).. We found that the individual response to a single-dose BDP against EIB has a predictive value for the efficacy of long-term treatment with BDP. This could support clinicians in providing personalized management of EIB in childhood asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Bronchoconstriction; Child; Exercise Test; Humans; Prospective Studies

A Markov cohort state transition model (focusing on exacerbations) was used to investigate the cost-effectiveness of medium- or high-dose BDP/FF/G vs medium- or high-dose BDP/FF, and high-dose BDP/FF/G vs high-dose BDP/FF + tiotropium. The model analysed cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER), and was developed from the England National Health Service perspective (2020 costs). Uncertainty of the inputs was estimated using one-way and probabilistic sensitivity analyses.. Both medium- and high-dose BDP/FF/G were cost-effective vs BDP/FF, with ICERs of £12,224 and £15,587 per QALY gained. High-dose BDP/FF/G was dominant vs BDP/FF + tiotropium, as it was both cheaper and gained QALYs. Sensitivity analyses were consistent with the base model: medium- and high-dose BDP/FF/G had 94.3% and 88.3% likelihoods to be cost-effective vs BDP/FF; high-dose BDP/FF/G had 100% likelihood to be a dominant strategy vs BDP/FF + tiotropium.. Both medium- and high-dose BDP/FF/G were cost-effective vs medium- and high-dose BDP/FF in adults with asthma that was uncontrolled by ICS/LABA. In addition, high-dose BDP/FF/G was a dominating strategy to high-dose BDP/FF + tiotropium.. GOV: NCT02676076 and NCT02676089.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Nebulizers and Vaporizers; State Medicine; Tiotropium Bromide

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

Topics: Asthma; Beclomethasone; Fluticasone; Humans; Propionates

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

Daily inhaled corticosteroids (ICSs) are fundamental to asthma management, but adherence is low.. To investigate (1) whether LC-MS/MS could be used to detect ICSs in serum and (2) whether serum levels related to markers of disease severity.. We collected blood samples over an 8-hour period from patients with severe asthma prescribed at least 1000 μg daily of beclomethasone dipropionate equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4, and 8 hours postinhalation and analyzed by LC-MS/MS. Correlations between serum ICS levels and severity markers were investigated.. A total of 60 patients were recruited (41 females; 39 prescribed maintenance prednisolone; mean age, 49 ± 12 years; FEV. Commonly used ICSs can be reliably detected in the blood at least 8 hours after dosing, and could therefore be used as a measure of adherence in severe asthma. Higher exacerbation rates and poorer lung function (for fluticasone propionate) were associated with lower blood levels.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chromatography, Liquid; Female; Fluticasone; Humans; Middle Aged; Tandem Mass Spectrometry

Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy.. Treatment with extrafine BDP/FF(200/6 μg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients.. Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 μg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Lung; Male; Maximal Midexpiratory Flow Rate; Metered Dose Inhalers; Middle Aged; Nitric Oxide; Phenotype; Pilot Projects; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Residual Volume; Smokers; Treatment Outcome; Vital Capacity

The present work aimed to study the role of metered-dose inhalers (MDI) verbal counseling on asthmatic children patients inhalation technique and their pulmonary functions.. In this study many children younger than 18 years old with asthma were collected from University hospital outpatient clinics throughout two years period Their MDI inhalation technique was checked and the number of MDI inhalation technique mistakes were detected and corrected at the first visit and every month for two more visits (three visits). Their peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV. 81 asthmatic subjects (54 female) younger than 18 years old were collected with a mean (SD) age 14.4 (1.8) years old. Most of the patients' owned MDI contained salbutamol, however, some patients were using Beclometasone MDI or Beclometasone and salbutamol combination MDI. The mean number of correct steps performed was significantly increased (p < 0.05) as the number of visits increased. "Place the MDI mouthpiece between the teeth and seal with lips" and "To maintain slow inhalation rate until lungs are full" were the least steps correctly performed by the asthmatics children studied. There was a significant increase (p < 0.05) in the pulmonary function test scores at the third visit.. MDI's verbal counseling should be repeated and checked at every opportunity, especially with children, to improve and maintain the recommended MDI inhalation technique. That could be a tool to possibly improve patients' pulmonary functions.

Topics: Administration, Inhalation; Adolescent; Albuterol; Asthma; Beclomethasone; Child; Counseling; Female; Humans; Male; Metered Dose Inhalers

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

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Female; Gene Expression; Humans; Male; Middle Aged; Nasal Mucosa

Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. However adverse effects of ICS on Hypothalamo Pituitary Adrenal (HPA) axis, growth and bone metabolism are a concern. Hence the primary objective of this study was to describe the effects of long term inhaled corticosteroid therapy (ICS) on adrenal function, growth and bone health in children with asthma in comparison to an age and sex matched group of children with asthma who were not on long term ICS. Describing the association between the dose of ICS and duration of therapy on the above parameters were secondary objectives.. Seventy children with asthma on ICS and 70 controls were studied. Diagnosis of asthma in selected patients was reviewed according to the criteria laid down by GINA 2018 guidelines. The estimated adult heights were interpreted relative to their Mid Parental Height (MPH) range. Serum calcium, alkaline phosphatase and vitamin D levels were analyzed in both groups and cortisol value at 30 min following a low dose short synacthen test was obtained from the study group. The average daily dose of ICS (Beclamethasone) was categorized as low, medium and high (100-200, 200-400, > 400 μg /day) respectively according to published literature.. Heights of all children were within the MPH range. There was no statistically significant difference in the bone profiles and vitamin D levels between the two groups (Ca: p = 0.554, vitamin D: p = 0.187) but vitamin D levels were insufficient (< 50 nmol/l) in 34% of cases and 41% of controls. Suppressed cortisol levels were seen in 24%. Doses of ICS were low, medium and high in 56, 32 and 12% of children respectively. The association between adrenal suppression with longer duration of therapy (p < 0.01) and with increasing dose of ICS (p < 0.001) were statistically significant.. ICS had no impact on the growth and bone profiles but its dose and duration were significantly associated with adrenal suppression.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Glands; Adrenal Insufficiency; Alkaline Phosphatase; Asthma; Beclomethasone; Body Height; Bone and Bones; Calcium; Case-Control Studies; Child; Child, Preschool; Female; Growth; Humans; Hydrocortisone; Male; Time Factors; Vitamin D

Co-prescription of Aerochamber

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Candidiasis, Oral; Female; Hoarseness; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged

A 91-year old female presented to Acute Medical Unit with a 2 week history of shortness of breath and haemoptysis. Her past medical history included osteoporosis, depression, irritable bowel syndrome, asthma, cataracts, and a colonic polypectomy. Her medications: Citalopram 10 mg, Co-codamol, Beclomethasone 200 mcg inhaler, Salbutamol MDI inhaler, Omeprazole 20 mg and Alendronic acid. She was an ex-smoker with a 20-pack year history who had stopped smoking 40-years ago. She did not drink alcohol and lived alone independently.

Topics: Aged, 80 and over; Asthma; Beclomethasone; Female; Humans; Metered Dose Inhalers; Nebulizers and Vaporizers; Radiography, Thoracic

Topics: Administration, Inhalation; Asthma; Beclomethasone; Eosinophils; Female; Humans; Leukocyte Count; Male

Lack of coordination between the beginning of the inhalation and device triggering is one of the most frequent errors reported in connection with the use of pMDI devices. Earlier results suggested a significant loss in lung deposition as a consequence of late actuation. However, most of our knowledge on the effect of poor synchronization is based on earlier works on CFC devices emitting large particles with high initial velocities. The aim of this study was to apply numerical techniques to analyse the effect of late device actuation on the lung dose of a HFA pMDI drug emitting high fraction of extrafine particles used in current asthma and COPD therapy. A computational fluid and particle dynamics model was combined with stochastic whole lung model to quantify the amount of drug depositing in the extrathoracic airways and in the lungs. High speed camera measurements were also performed to characterize the emitted spray plume. Our results have shown that for the studied pMDI drug late actuation leads to reasonable loss in terms of lung dose, unless it happens in the second half of the inhalation period. Device actuation at the middle of the inhalation caused less than 25% lung dose reduction relative to the value characterizing perfect coordination, if the inhalation time was between 2 and 5 s and inhalation flow rate between 30 and 150 L/min. This dose loss is lower than the previously known values of CFC devices and further support the practice of triggering the device shortly after the beginning of the inhalation instead of forcing a perfect synchronization and risking mishandling and poor drug deposition.

Topics: Administration, Inhalation; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Combinations; Formoterol Fumarate; Humans; Hydrodynamics; Lung; Metered Dose Inhalers; Models, Biological; Pulmonary Disease, Chronic Obstructive; Time Factors

To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.. The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.. SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.. The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.

Topics: A549 Cells; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Fluids; Fluticasone; Humans; Lung; Solubility

The breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Dry Powder Inhalers; Formoterol Fumarate; Humans; Lung; Models, Biological; Particle Size; Respiration

The impact of inhaled corticosteroids (ICS) on eosinophilic inflammation in asthma is well established, but their effect in a real-life setting has not been extensively studied. Our purpose was to investigate the effect of ICS on airway and systemic inflammation as well as on clinical outcomes in patients with asthma from clinical practice.. We conducted a retrospective analysis on asthmatics from a secondary care centre in whom ICS were initiated/increased (n=101), stopped/decreased (n=60) or remained stable (n=63, used as a control group) between two visits with available sputum and blood cell counts.. Our results confirm the effectiveness of ICS on eosinophilic inflammation in real life and demonstrate that their clinical benefit seems to be restricted to eosinophilic asthmatics. Our data also support a try for stepping-down ICS in non-eosinophilic asthmatics.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Case-Control Studies; Dose-Response Relationship, Drug; Eosinophils; Female; Forced Expiratory Volume; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Retrospective Studies; Sputum

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Male; Medication Adherence; Middle Aged; Pilot Projects; Treatment Adherence and Compliance; Young Adult

INTRODUCTION    Asthma is a highly prevalent disease that often requires maintenance therapy. Combined inhaled corticosteroid (ICS) and long‑acting β2‑agonist (LABA) inhalers are one of the available maintenance treatment options. OBJECTIVES    This prospective observational study aimed to assess asthma control in patients treated with ICS/LABA inhalers and to identify factors related to optimal asthma control. PATIENTS AND METHODS    The study included 5789 asthmatic patients from Poland, treated with one of the following ICS/LABA inhalers at clinically appropriate doses: beclomethasone/formoterol, fluticasone/ salmeterol, or budesonide/formoterol. The follow‑up lasted 6 months (4 visits in total). The outcomes were physician-reported and patient‑reported asthma control and occurrence of adverse drug reactions. A retrospective logistic regression analysis was performed to identify a potential association between age, obesity, and smoking and the level of disease control. RESULTS    A total of 4469 patients completed the study. Throughout the study period, the rate of patient‑reported control of asthma increased from 24.8% to 67.7%, while physician‑reported control increased from 22.6% to 66.4%. The incidence of exacerbations decreased from 23.4% to 1.9%. Less than 0.1% of the patients reported adverse drug reactions. Age, obesity (body mass index ≥30 kg/m2), and smoking were confirmed as factors negatively affecting disease control, with combined ICS/LABA inhalers potentially reducing their effect. CONCLUSION    Our results confirm the efficacy and safety of combined ICS/LABA inhalers in a real‑life clinical setting. They also corroborate the finding that obesity, older age, and smoking are risk factors for poor asthma control.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Therapy, Combination; Female; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

The asthmatic patient's respiratory tract deposition of HFA fluticasone (Flovent HFA(™)) has not been established. There is a known large particle size difference with another commercial inhaled HFA steroid (QVAR(™)). This study compared the 2D and 3D respiratory tract deposition of each inhaled steroid.. This study was an open label, crossover study in eight patients diagnosed with asthma. The regional respiratory and oropharyngeal deposition of the two steroids were compared and contrasted using planar and SPECT imaging following delivery of the (99m)Tc-radiolabeled drug in each product. The SPECT images were merged with computed tomography images to quantify regional deposition within the patients.. Two-dimensional (2D) planar images indicated that 24% of the Flovent HFA dose and 55% of the QVAR dose deposited in the lungs. 2D oropharyngeal deposition indicated that 75% of the Flovent HFA dose was deposited in the oropharynx, while 42% of the QVAR dose deposited in the oropharynx. Three-dimensional (3D) SPECT data indicated that 22% of the Flovent HFA dose and 53% of the QVAR dose deposited in the lungs. 3D oropharyngeal and gut deposition indicated 78% of the Flovent HFA dose was deposited in the oropharynx, while 47% of the QVAR dose deposited in the oropharynx. The increased lung deposition and decreased oropharynx deposition for both 2D and 3D image data of QVAR were statistically different from Flovent HFA.. QVAR exhibited a significant increase in lung delivery compared to Flovent HFA. Conversely, QVAR delivered a significantly lower dose to the oropharynx than Flovent HFA. The findings were presumed to be driven by the smaller particle size of QVAR (0.7 microns MMAD) compared with Flovent HFA (2.0 microns MMAD).

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Drug Compounding; Fluticasone; Humans; Hydrocarbons, Fluorinated; Lung; Male; Metered Dose Inhalers; Middle Aged; Multimodal Imaging; Oropharynx; Particle Size; Radiographic Image Interpretation, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Young Adult

The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances.. The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain.. Breath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs.. The multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Capsules; Chemistry, Pharmaceutical; Dry Powder Inhalers; Female; Formoterol Fumarate; Humans; Inspiratory Capacity; Male; Middle Aged; Multivariate Analysis; Particle Size; Pharynx; Powders; Respiration; Young Adult

Topics: Administration, Inhalation; Aminopyridines; Androstadienes; Asthma; Beclomethasone; Benzamides; Cyclopropanes; Humans; Indans; Maleates; Nasal Sprays; Powders; Pulmonary Disease, Chronic Obstructive; Quinolones; Respiratory Tract Diseases; Rhinitis, Allergic

This study aims to assess voice changes and laryngeal abnormalities in asthmatic patients using inhaled corticosteroids (ICSs).. This study included 30 patients (15 females; mean age 21.3±2.6 years; range, 17 to 26 years and 15 males; mean age 20.7±2.3 years; range, 16 to 27 years) with bronchial asthma treated with ICSs between May 2013 and December 2013. A speech sample from each patient was evaluated by two phoniatricians and the degrees of dysphonia were scored. Each patient's voice was acoustically analyzed using the multidimensional voice program software. Videolaryngoscopy was used to detect laryngeal abnormalities including the vocal folds.. A total of 53.3% of ICSs users had dysphonia; most of them had a mild degree dysphonia. Of patients, vocal folds erythema was present in 56.7%, interarytenoid thickening in 56.7%, vocal folds bowing in 5.3% and vocal fold atrophy in 5.5%. A total of 36.7% patients had manifestations of laryngopharyngeal reflux. The presence of vocal fold bowing and atrophy was significantly related to the duration of ICS use (p=0.048). Soft phonation index values were positively associated with the duration of the ICS use (p=0.013).. Inhaled corticosteroids have abnormally adverse effects both on the function and the structure of the vocal folds.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Atrophy; Beclomethasone; Budesonide; Dysphonia; Erythema; Female; Glucocorticoids; Humans; Laryngeal Diseases; Laryngoscopy; Male; Nebulizers and Vaporizers; Phonation; Speech; Video Recording; Vocal Cords; Voice; Young Adult

Topics: Administration, Inhalation; Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Child; Child Development; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Puberty; Rhinitis, Allergic

Scant clinical data are available on the effects of current treatments for asthma on different subgroups of patients with this disease. We conducted a prospective, noninterventional, multicenter real-life study in adult patients with persistent asthma, and we specifically analyzed the effects of treatment with extrafine beclometasone dipropionate/formoterol (BDP/F) in asthma patients categorized by phenotypes related to small airways (i.e. smoking habits, disease duration, and air trapping).. Patients received BDP/F as a fixed combination (100/6 μg), administered in 1-2 inhalations twice daily over a period of 12 weeks. Peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), number of asthma attacks, asthma control, and severity of asthma symptoms were evaluated in the overall population and in different subgroups at three different time points.. Overall, 213 patients were enrolled. In the overall population the treatment resulted in a significant increase in the proportion of well controlled patients (from 6.1% to 66.3%; p<0.001), and a reduction of uncontrolled subjects (70.3% versus 10.0%; p<0.001). BDP/F was also associated with a reduction in asthma attacks and an improvement of symptoms. These results were confirmed in specific subgroups of patients identified as small airway phenotypes: smokers, elderly patients, those with long duration of disease and air trapping.. This real-life observational study indicates that extrafine BDP/F in a fixed combination improves asthma control and symptoms in the overall population as well as specific subgroups of patients.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Drug Combinations; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Phenotype; Prospective Studies; Smoking; Time Factors; Treatment Outcome; Vital Capacity

Topics: Adult; Asthma; Beclomethasone; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Combinations; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Respiratory Hypersensitivity; Young Adult

Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands.. Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting β2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models.. Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in μg) were 160 (160 - 320) for extrafine-particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]).. In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cohort Studies; Databases, Factual; Female; Fluticasone; Humans; Logistic Models; Male; Middle Aged; Netherlands; Particle Size; Pregnenediones; Treatment Outcome

The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice.. Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done.. Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation.. Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.

Topics: Airway Remodeling; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoalveolar Lavage Fluid; Chronic Disease; Collagen; Disease Models, Animal; Drug Evaluation, Preclinical; Interleukin-13; Leukocyte Count; Lung; Male; Mice; Nitric Oxide; ortho-Aminobenzoates; Transforming Growth Factor beta1

Since June 2011, the Brazilian health system started providing asthma medications (beclomethasone and salbutamol), totally free of charge to patients with asthma. The aim of this study was to evaluate the impact of the provision of free asthma medications on hospital admissions for asthma in Brazil, using a national hospitalization database (DATASUS), comparing the incidence of hospital admissions before and after the free supply of these drugs.. Admissions of patients with 1-49 years of age by the Brazilian public health system with the diagnosis of asthma were compared pre (2008-2010) and post (2012-2014) provision of free medicines (beclomethasone and salbutamol). The number of hospital admissions due to asthma and non-respiratory diseases, as well as the amount spent with asthma hospitalization, were obtained from DATASUS, the Brazilian government open-access public health database system.. Admission rates for asthma significantly decreased from 90.09/100.000 (2008-2010) to 59.85/100.000 (2012-2014), when the period pre and post provision of free medicines were compared [OR 0.67 (CI 0.48-0.92)]. Non-respiratory admission rates remained stable, when both periods were also compared.. Asthma hospitalization rates significantly decreased in the three-year period after the provision of free medicines to treat asthma. Our findings suggest that the provision of free medications for asthma may have a particular public health impact by its own in developing countries.

Topics: Adolescent; Adult; Age Distribution; Albuterol; Anti-Asthmatic Agents; Asthma; Beclomethasone; Brazil; Child; Child, Preschool; Databases, Factual; Drug Costs; Female; Glucocorticoids; Health Care Costs; Hospitalization; Humans; Infant; Male; Middle Aged

The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS.. Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day(-1) ) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers.. The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1 ) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1 , but had no effect on FEV1 at 24 h after challenge or sputum measurements.. The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchoconstriction; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Spirometry; Surveys and Questionnaires

Topics: Anti-Asthmatic Agents; Asthma; Beclomethasone; Eosinophilia; Eosinophils; Humans; Leukocyte Count; Predictive Value of Tests; Prednisone; Severity of Illness Index; Sputum; Th2 Cells; Triamcinolone

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Aryl Hydrocarbon Hydroxylases; Asthma; Beclomethasone; Child; Child, Preschool; Cytochrome P-450 CYP3A; Disease Management; Female; Gene Expression; Humans; Male; Polymorphism, Single Nucleotide; Treatment Outcome

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Age Distribution; Aged; Androstadienes; Asthma; Beclomethasone; Cohort Studies; Fluticasone; Humans; Middle Aged; Smoking; Smoking Cessation; Treatment Outcome; United Kingdom

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

Age and sex are associated with differences in asthma prevalence and morbidity.. To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma.. We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003.. A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P < 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P < 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P < 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088).. Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.

Topics: Administration, Inhalation; Adult; Age Factors; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Cohort Studies; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Logistic Models; Male; Odds Ratio; Phenotype; Retrospective Studies; Sex Factors; Treatment Failure; Treatment Outcome

INTR​ODUCTION: Asthma is one of the most common health problems, and its poor control can seriously affect patients' lives.. We assessed the level of asthma control in a real-life setting in Poland, in outpatients treated with a beclomethasone and formoterol combination pressurized metered-dose inhaler (BDP/F-pMDI).. The study lasted for 6 months (3 visits). Patients were aged 18 years or older, were diagnosed with asthma at least 12 months before the inclusion to the study, and had been using BDP/F-pMDI hydrofluoroalkanes (HFA) for a minimum of 2 weeks before the enrollment. Asthma control was determined in accordance with the criteria of the Global Initiative for Asthma. Patients' data were collected during study visits, using unified questionnaires with close-ended questions.. During the first visit, 8.6% of the patients had controlled asthma; 27.6%, partly controlled asthma; and 63.9%, uncontrolled asthma. Poorer control of asthma was observed in men, smokers, patients with a longer history of asthma, higher body mass index, lower physical activity, shorter treatment with BDP/F-pMDI HFA, and inaccurate inhaler technique. After 6 months of therapy, asthma control improved in 74.2% of the patients; 60.1% of the patients met the criteria of controlled asthma; 31.4%, of partly controlled asthma; and 8.3%, of uncontrolled asthma.. The use of BDP/F-pMDI HFA was effective in the long-term control of asthma, and one of the important factors improving treatment outcomes is the training of patients in the correct inhaler technique.

Topics: Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Disease Management; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Poland; Surveys and Questionnaires; Treatment Outcome; Young Adult

Oxidative stress is thought to play a role in the pathogenesis of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has antioxidant properties. The function and expression of clusterin in patients with asthma have not been fully investigated.. To investigate whether the expression of clusterin in patients with asthma is regulated by increased oxidative burden and whether clusterin expression could be used to assess the response to inhaled corticosteroids.. Clusterin levels in serum, induced sputum, and peripheral blood mononuclear cells of patients with asthma were measured by enzyme-linked immunosorbent assay and western blotting and compared with pulmonary function and levels of expression of hyperoxidized peroxiredoxins. Serum concentrations of clusterin in treatment-naive patients were compared before and after inhaled corticosteroid use.. Serum clusterin concentration was significantly elevated in patients with severe asthma and was inversely correlated with pulmonary function. The expression of hyperoxidized peroxiredoxins was greatly increased in peripheral blood mononuclear cells of patients with asthma and was strongly correlated with clusterin expression. Serum clusterin concentrations in treatment-naive patients with asthma were decreased significantly after initial treatment with inhaled corticosteroids.. Clusterin may be a biomarker of asthma severity and the burden of oxidative stress in patients with asthma. Moreover, clusterin may be useful for the prompt assessment of airway inflammation.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biomarkers; Clusterin; Female; Forced Expiratory Volume; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress; Peroxiredoxins; Respiratory Function Tests; Sputum

Topics: Adrenal Cortex Hormones; Aged; Airway Obstruction; Asthma; Beclomethasone; Bronchodilator Agents; Clinical Trials as Topic; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oscillometry; Prednisolone; Reproducibility of Results; Surveys and Questionnaires

To evaluate the clinical efficiency of tactics to widen the scope of monotherapy with inhaled glucocorticosteroids (IGCS) in asthmatic patients with bronchial cold hyperreactivity (BCHR) during winter to achieve control of the disease in real clinical practice.. An open-label longitudinal study was conducted in a cold period in 106 asthmatics divided into 2 groups: 1) those with BCHR and 2) those with unchanged bronchial reactivity to a cold stimulus. The study involved monitoring the symptoms by the asthma control test, peak expiratory flow rate (PEFR), and spirometry results before and after cold bronchoprovocation testing; assessment of the pattern of bronchial inflammation from the ratios of induced sputum (IS) cell populations; and estimation of the number of asthma exacerbations and emergency care recourses. Group 1 used a stepwise increase of the scope of basic therapy with beclomethasone dipropionate 1000 microg/day until asthma control was achieved, which was followed by the therapy with the stable dose. Group 2 received monotherapy with beclomethasone dipropionate as the stable dosage of < or = 500 microg/day.. After the first 12 weeks of a follow-up, Group 1 showed the most marked positive changes in the intensity of clinical symptoms, forced expiratory volume in one second, and PEFR that remained within the following 12 weeks during the continued therapy with the stable dose of the drug. A preponderance of the eosinophilic and neutrophilic pattern of inflammation was seen in the patients of this group. By the end of the study, there was a decline in the number of IS inflammatory cells. A discriminant model was developed as a tool to predict asthma control achievement in patients with BCHR.. A stepwise increase in the scope of IGCS monotherapy in asthmatic patients with BCHR during winter can yield the results of disease control and the incidence of exacerbations, which are similar to those seen in asthmatics with no signs of BCHR (53 and 49%, respectively).

Topics: Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Cold Temperature; Discriminant Analysis; Disease Management; Disease Progression; Emergency Medical Services; Female; Humans; Longitudinal Studies; Male; Middle Aged; Respiratory Function Tests; Russia; Seasons

Glucocorticoids are the most effective anti-inflammatory treatment for allergic diseases, and inhaled glucocorticoids have now become the first-line treatment for asthma. Glucocorticoids were discovered in the 1940s as extracts of the adrenal cortex and this was followed by the isolation of adrenocorticotropic hormone (ACTH) from pituitary gland extracts. Cortisone and ACTH were found to be very beneficial in the treatment of rheumatoid arthritis and Kendall, Reichstein and Hench received the Nobel Prize in Physiology and Medicine for this work in 1950. Bordley and colleagues first showed that ACTH was very beneficial in the treatment of allergic diseases in 1949, but the use of systemic glucocorticoids was limited by side effects. Inhaled glucocorticoids were discovered from topical steroids developed for skin inflammation and beclomethasone dipropionate was introduced in 1972, initially in low doses but later in higher doses, and became the standard treatment for persistent asthma. Subsequently, inhaled glucocorticoids were combined with long-acting β2-agonists in combination inhalers for even greater therapeutic benefit. There is now a good understanding of the molecular basis for the anti-inflammatory effects of glucocorticoids in allergic diseases. The search for even safer glucocorticoids based on the dissociation of anti-inflammatory and side effect mechanisms is currently ongoing.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Beclomethasone; Drug Therapy, Combination; Glucocorticoids; History, 20th Century; Humans

Topics: Aerosols; Asthma; Beclomethasone; Eosinophils; History, 20th Century; Humans; Steroids; United Kingdom

Most asthmatics have been found to have rhinosinusitis (RS). Patients with ethmoid sinusitis, in particular, often suffer from an impaired sense of smell; this is clinically important and necessitates concurrent treatment for both asthma and RS. As a rational therapeutic strategy, we focused on a fine particle HFA-134abeclomethasone dipropionate (HFA-BDP) metered-dose inhaler. Because of its small size, the medication is still present in the exhaled breath after inhalation.. Five mild-to-moderate asthmatics with ethomoidpredominant sinusitis characterized by an impaired sense of smell and mild peripheral blood eosinophilia received a single-agent treatment with orally-inhaled HFA-BDP which was then exhaled through the nose. In addition, the stained small particles were created by an ultrasonic nebulizer and flow image of them during oral inhalation and nasal exhalation was evaluated by using nasal endoscopy.. After treatment, the sense of smell was restored in all cases with a concomitant improvement in sinusitis as confirmed by computerized tomography. In addition, amelioration of peripheral blood eosinophilia as well as small airway obstruction as indicated by pulmonary function tests was observed. Macroscopical imaging revealed that small particles flow toward olfactory cleft during both the inhalation and exhalation phases.. We have presented 5 cases of asthmatic patients with RS treated with a concurrent single therapy, HFA-BDP exhaled through the nose (ETN). A clinical trial must be considered to establish this new therapeutic strategy based on the concept of "one airway, one disease."

Topics: Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Metered Dose Inhalers; Middle Aged; Rhinitis; Sinusitis