Effects of terbutaline and budesonide on sputum cells and bronchial hyperresponsiveness in asthma

Previous studies have shown that the regular administration of short acting beta-agonists can be associated with adverse effects on airway caliber and bronchial hyperresponsiveness (BHR) and that this may occur through a proi nflammatory mechanism. The aim was to explore possible adverse effects of h igh-dose beta-agonist therapy and to assess any adverse interaction with co rticosteroids. We undertook a randomized, crossover study to investigate th e effects of 6 wk of treatment with regular terbutaline (1 mg four times a day), regular budesonide (400 mu g twice a day), combined treatment, and pl acebo in subjects with mild to moderate asthma. Major endpoints were PD15 s aline, PD20 methacholine, and induced sputum differential cell counts. Thir ty-four subjects were randomized and 28 completed the study. PD15 saline de creased on terbutaline alone compared with placebo treatment and on combine d treatment compared with budesonide alone (mean fold decrease of 0.57 [95% CI = 0.36, 0.90] and 0.65 [95% Cl = 0.43, 0.97], respectively). PD20 metha choline was not affected by the use of terbutaline either alone or in combi nation with budesonide. The percentage of eosinophils in induced sputum inc reased during terbutaline treatment alone compared with placebo (median 8.3 % versus 4.4%, p = 0.049). The addition of terbutaline to budesonide did no t affect the percentage of eosinophils compared with budesonide treatment a lone. These findings support the hypothesis that short-acting p-agonists ha ve a permissive effect on airway inflammation and that when used in high do se there may be an unfavorable interaction with inhaled corticosteroids.