A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic asthmatic patients

Background: Some recent studies suggest that regular beta (2)-agonist use m ay result in inadequate control of asthma, It has been hypothesized that th is occurs particularly in allergic asthmatic patients exposed to relevant a llergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta (2)-agonists. Methods: Asthmatic patients (n=145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta (2)-agonist (SA; n = 48), a long-acting beta (2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introd uction of allergen avoidance measures (active/placebo treatment) to lower H DM exposure in the active group, and an 8-week washout period to adjust pat ients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter , spirometric measurements (FEV1 and provocative concentration of histamine causing a 20% fall in FEV1 [PC20]) were performed. Peak flow and asthma sy mptoms were recorded daily. Additionally, at die start and every 6 weeks th ereafter, dust samples were collected from mattresses and Living room and b edroom floors to assess HDM (der p 1) concentrations, Effects on FEV1, PC20 , peak flow, and asthma symptoms were analyzed with repeated-measurement an alysis and corrected for the exposure to HDM allergens. Results: There were no significant differences among the three medication g roups after 12 weeks for FEV1. However, a significant decrease in mean FEV1 percent predicted (95% confidence interval [CI]) was observed within the S A group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002), A decrease in geometric mean PC20 (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was obser ved within the SA group (p = 0.05). No significant changes in FEV1 and PC20 were observed > 12 weeks within the LA group or the placebo group. There w ere neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Morover, none of the parameters sh owed interactive effects with allergen exposure. Conclusion: There were no significant differences among the three medicatio n groups for FEV1 and PC20. The within-treatment group comparison showed a significant small decline in FEV1 for the SA group (but not for the LA grou p), which could indicate that monotherapy with SAs might have negative effe cts on FEV1. This was not seen during regular use of LAs. No clear pathophy siologic mechanism can explain these findings at the moment. Relatively hig h or low exposure to allergens did not alter these findings.