Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma

Background: Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects. Objective: We sought to evaluate exercise-induced broncho-constriction (EIB) as a method of determining the dose and time responses of inhaled corticosteroid therapy. Methods: In this double-blind, randomized, cross-over study with 2 parallel arms, 4 doses of inhaled ciclesonide (40 mu g and 160 mu g or 80 mu g and 320 mu g) were compared over 3 weeks of treatment. Twenty-six asthmatic subjects (age range, 14-27 years) with baseline FEV1 values of greater than 70% of predicted value were enrolled. The primary outcome was the maximum percentage decrease in FEV1 after standardized exercise challenge. Results: After 1 week of therapy, the mean +/- SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-mu g/80-mu g dose group was 9% 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-mu g/320-mu g dose group, there was an 8.7% +/- 2.5% (95% CI, 3.7% to 13.7%) reduction in maximum decrease in FEV1 after week 1, which continued in a linear fashion during subsequent weeks of treatment. No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment. The maximum percentage attenuation in EIB achieved was 51.1% +/- 7.9%, which was achieved by using the 320-mu g dose after 3 weeks of treatment. Conclusions: A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 mu g/320 mu g of ciclesonide resulted in a continuing improvement in FEV1 with time, and no plateau was seen in protective effect during 3 weeks of treatment. Clinical implications: Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 mu g. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 mu g, even after 3 weeks of therapy.