Subsittution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics. A comparison of triamcinolone acetonide MDI with a built-in tube extender and beclomethasone dipropionate MDI in adult asthmatics. A comparison of double-strength beclomethasone dipropionate (84 microg) MDI with beclomethasone dipropionate (42 microg) MDI in the treatment of asthma. Aerosol beclomethasone dipropionate in chronic bronchial asthma. Beclomethasone dipropionate aerosol in the treatment of steroid-dependent asthma. A 12-week double-blind study comparing beclomethasone dipropionate and a vehicle aerosol. Effect of inhaled beclomethasone dipropionate on isocapnic hyperventilation with cold air in asthmatics, measured with forced oscillation technique. Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol. Effects of inhaled beclomethasone on airway responsiveness in occupational asthma. Placebo-controlled study of subjects sensitized to toluene diisocyanate. Steroid-dependent asthma treated with inhaled beclomethasone dipropionate. A long-term study. Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma. Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma. High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients. Comparative clinical study of inhaled beclomethasone dipropionate and triamcinolone acetonide in persistent asthma. Systemic side effects of beclomethasone dipropionate aerosols (becotide, aldecine, sanasthmyl) in otherwise non steroid treated asthmatic patients. Effect of beclomethasone dipropionate on the bronchial responsiveness to propranolol in asthmatics. Beclomethasone dipropionate aerosol in asthma--a double blind study. Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics. Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group. Effect of inhaled beclomethasone dipropionate on bronchial hyperreactivity in asthmatic children during maximal allergen exposure. A controlled trial of inhaled corticosteroids in patients receiving Prednisone tablets for asthma. Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects. Effects of regular inhalation of beclomethasone dipropionate and sodium cromoglycate on bronchial hyperreactivity in asthmatic children. Increased airway responsiveness in children of low birth weight at school age: effect of topical corticosteroids. Preventive effects of beclomethasone on histamine-induced changes in breathing pattern in asthma. Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. A controlled trial of beclomethasone dipropionate in asthma. Comparison of the effects of inhaled corticosteroids on the airway response to histamine, methacholine, hyperventilation, and sulfur dioxide in subjects with asthma. Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma. Beclomethasone dipropionate aerosol in adult steroid-dependent obstructive lung disease. A comparison of betamethasone valerate, beclomethasone dipropionate and placebo by inhalation for the treatment of chronic asthma. A clinical trial of beclomethasone dipropionate aerosol in children and adolescents with asthma. A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma. Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma: a 12-week, randomized, double-blind, placebo-controlled study. Treatment of chronic childhood asthma with beclomethasone dipropionate aerosol: I. A double-blind crossover trial in nonsteroid-dependent patients. Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, placebo controlled trial. Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation. A controlled trial of beclomethasone dipropionate for asthma. A placebo-controlled blinded comparison of nedocromil sodium and beclomethasone dipropionate in bronchial asthma. Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma. Beclomethasone dipropionate aerosol in asthma. Transfer of steroid-dependent asthmatic patients from oral prednisone to beclomethasone dipropionate aerosol. Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma. Effect of inhaled beclomethasone dipropionate on bronchial responsiveness in patients with asthma. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group. Effects of inhaled steroids on blood eosinophils in moderate asthma. Beclomethasone dipropionate by aerosol in the treatment in asthmatic children. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study. A controlled trial of beclomethasone dipropionate by aerosol in chronic asthmatics. The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects.
The effect of inhaled beclomethasone dipropionate (dose, 400 mug daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14. 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. 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. nan 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. 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. 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. 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) 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. 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. 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. 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. 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. nan 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. nan 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. 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. 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. 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. 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) 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. The effect of treatment with topical inhaled corticosteroids was assessed in 15 children of low birth weight (mean (SD) birth weight 1435 (268) g, gestational age 30.5 (2.9) weeks, age at study 8.2 (0.4) years) who were symptomatic and showed a positive airway response to histamine aerosol. The study was of a double blind, placebo controlled, crossover design with four week long treatment periods with inhaled beclomethasone dipropionate (400 micrograms daily) or placebo. Daily symptom scores were recorded and physiological measurements were performed at the beginning and end of each treatment period. There was no significant difference in respiratory symptom score, baseline airway function, or the airway response to histamine between treatment periods. The findings argue against an inflammatory basis for airway hyper-responsiveness in these children and raise questions as to its pathophysiological basis. 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. Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma. 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. nan 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) 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. nan nan nan 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. Beclomethasone dipropionate (BDP) has been formulated as an extrafine aerosol (hydrofluoroalkane-134a [HFA]-BDP) [QVAR; 3M Pharmaceuticals; St Paul, MN], which gives improved lung deposition compared with chlorofluorocarbon (CFC)-BDP. The clinical efficacy of HFA-BDP has been established in adult asthma at a required dose below that of CFC-BDP, but has not been evaluated in children.
                To examine the efficacy and safety of HFA-BDP in childhood asthma.
                A 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study involving 353 children aged 5 to 12 years with moderate, symptomatic asthma. After a 2-week run-in period, patients were randomized to HFA-BDP, 80 micro g/d (n = 120); HFA-BDP, 160 micro g/d (n = 117); or HFA-placebo (n = 116) administered twice daily.
                Hospital outpatient.
                HFA-BDP, 80 micro g/d and 160 micro g/d, produced a significant, dose-related increase from baseline in FEV(1) percent predicted compared with placebo. At week 12, mean changes from baseline in FEV(1) percent predicted were 9.2% (p < or = 0.01 vs placebo), 10% (p < or = 0.01 vs placebo), and 3.9% for the HFA-BDP 80 micro g/d, HFA-BDP 160 micro g/d, and placebo groups, respectively. There was also a significant decrease in daily beta-agonist use, improvement in peak expiratory flow, and increase [correction] in the percentage of days free from asthma symptoms (p < or = 0.05 for HFA-BDP, 160 micro g/d, vs placebo at weeks 11 to 12). HFA-BDP was well tolerated, with no significant differences in the incidence or nature of adverse events between HFA-BDP and placebo groups. Neither were there significant differences between groups in mean percentage change from baseline in the morning plasma cortisol level at week 12 or in the percentage of patients with morning plasma cortisol levels below the reference range at baseline and week 12. In a subgroup tested, the percentage of patients with an abnormal response to low-dose adrenocorticotropic hormone stimulation at week 12 was low and similar among all groups.
                HFA-BDP, 80 to 160 micro g/d, is effective and safe in childhood asthma. nan Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma.
                To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property.
                Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 mg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 mg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis.
                Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters.
                These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist. 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. nan 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. 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. nan 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. 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. 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. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.
                In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.
                Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group.
                The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease. nan nan 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. 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. nan 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)
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.