Volume 117, Issue 5 , Pages 1008-1013, May 2006
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 bronchoconstriction (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 μg and 160 μg or 80 μg and 320 μg) 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-μg/80-μg dose group was 9% ± 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-μg/320-μg 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-μg dose after 3 weeks of treatment.
Conclusions
A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 μg/320 μg 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 μg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 μg, even after 3 weeks of therapy.
Key words: Asthma, exercise induced, inhaled corticosteroids, randomized controlled trial, dose response
Abbreviations used: AUC, Area under the curve, EIB, Exercise-induced bronchoconstriction, ICS, Inhaled corticosteroid, PEF, Peak expiratory flow
Some of the data from this article have been presented in abstract form at the American Academy of Allergy, Asthma and Immunology Meeting, San Antonio, Tex, March 2005, and the American Thoracic Society Meeting, San Diego, Calif, May 2005.Supported in part by Altana Pharma AG, Germany.Disclosure of potential conflict of interest: S. Pedersen has consultant arrangements with Altana and GlaxoSmithKline and has received grants from AstraZeneca, Altana and GlaxoSmithKline. P. O'Byrne has consultant arrangements with Altana, AstraZeneca, Biolipox, GlaxoSmithKline, Oxygen, Topigen and Roche and has received grants from Altana, AstraZeneca, Biolipox, GlaxoSmithKline, and Pfizer. The rest of the authors have declared that they have no conflict of interest.
PII: S0091-6749(06)00195-3
doi:10.1016/j.jaci.2005.11.048
© 2006 American Academy of Allergy, Asthma and Immunology. Published by Elsevier Inc. All rights reserved.
Volume 117, Issue 5 , Pages 1008-1013, May 2006
