The effect of inhaled ciclesonide on airway blood flow

Background: In addition to their genomic anti-inflammatory actions, inhaled corticosteroids are known to induce acute airway responses through nongenomic mechanisms in asthma. We have previously demonstrated that a single dose of fluticasone caused a rapid, dose-dependent decrease in airway blood flow (Qaw) in subjects with asthma. Although suppression of airway inflammation can reverse airway hyperperfusion, the role of the classical genomic corticosteroid mechanisms in the airway vasoconstriction is not known. Objective: The purpose of the study was to determine whether ciclesonide, a prodrug inhaled corticosteroid with weak glucocorticoid receptor binding affinity, similarly leads to vasoconstriction in the airway mucosa. Methods: Ten healthy non-smoker volunteers participated in the study. Qaw levels were determined before and 15, 30 and 60 min after inhalation of ciclesonide (320 μg), fluticasone (500 μg) or placebo. A soluble, inert gas-uptake method was used to measure Qaw. Results: Ciclesonide and fluticasone produced a rapid decrease in mean Qaw levels without a nadir up to 60 min. After ciclesonide inhalation, the maximum mean Qaw decrease was 39% (from 56.1±4 to 34.1±4.7 μl/ml/min; p Conclusion: In healthy subjects, inhaled ciclesonide and fluticasone caused a vasoconstriction in the airway demonstrating a corticosteroid action that is not related to the anti-inflammatory effects of these drugs. The prodrug ciclesonide induced reduction of Qaw suggests a mechanism for airway vasoconstriction other than the genomic mechanism of corticosteroids.