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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.

The National Asthma Education and Prevention Program (NAEPP) Expert Panel II recommended a stepped care pharmacotherapy approach to asthma treatment based on an objective assessment of asthma severity using daytime symptoms, nocturnal symptoms, and physiologic lung function. The worst grade of the individual variables determines overall asthma severity. With this approach, patterns of asthma severity categorization might vary among individual variables; one variable might have a predominant effect on overall categorization. During the run-in, pretreatment phase of five controlled clinical trials, data from 744 inhaled steroid nonusers and 685 inhaled steroid users on asthma control were collected and asthma severity categorized. In inhaled steroid nonusers nocturnal symptoms classified the majority of patients as severe, persistent, but wheeze classified 27.3% of patients as mild, intermittent and 25.7% as mild, persistent. If the worst grade from the four asthma symptoms was used for severity grading, most patients were categorized as severe, persistent. beta-Agonist use and FEV(1) classified most as moderate, persistent. There was poor correlation between variables in severity categorization. Severity grading for European patients was similar to that for U.S. patients. Applying the Expert Panel II recommended method for asthma severity categorization to a large data set illustrates that a single variable, nocturnal symptoms, determined to a large extent overall categorization. Development of a validated method for asthma severity categorization is essential for using a stepped care approach to asthma pharmacotherapy.

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