A dose-dependent effect of the novel inhaled corticosteroid ciclesonide onairway responsiveness to adenosine-5 '-monophosphate in asthmatic patients

Inhaled corticosteroids decrease airway responsiveness in asthma partly thr ough suppression of airway inflammation. We have previously demonstrated th at inhaled budesonide reduced airway responsiveness to the mast cell stimul us adenosine-5'-monophosphate (AMP) to a threefold greater extent than to m ethacholine and sodium metabisulfite, suggesting that AMP responsiveness ma y be a more sensitive marker of airway inflammation and steroid action in o rder to assess a dose-response relationship. To investigate this, we studie d the effects of three doses of the novel corticosteroid ciclesonide (50 mu g, 200 mu g, and 800 mu g) inhaled as a dry powder twice daily on airway r esponsiveness to AMP and inflammatory parameters in induced sputum. in a th ree-parallel-dose group, double-blind, placebo-controlled, randomized, cros sover study, with a washout period of 3 to 8 wk, a total of 29 patients wit h mild to moderate allergic asthma underwent AMP challenge and sputum induc tion before and after 14 d of treatment with ciclesonide or matched placebo . Compared with placebo, ciclesonide 100 mu g, 400 mu g, and 1,600 mu g dai ly reduced airway responsiveness to AMP by 1.6 (95% confidence interval [CI ], -0.1 to 3.4, not significant [NS]), 2.0 (95% CI, 0.4 to 3.6, p < 0.05), and 3.4 (95% CI, 2.3 to 4.4, p < 0.05) doubling doses, respectively, and th is reduction in airway responsiveness was dose-dependent (p = 0.039). A sig nificant reduction in the percentage of eosinophils in induced sputum was o bserved after 400 mu g and 1,600 mu g daily ciclesonide (p < 0.05), but thi s was not dose-dependent. Sputum eosinophil cationic protein (ECP) was sign ificantly reduced after 400 mu g daily ciclesonide only (p < 0.05). Thus, i n patients with mild to moderate asthma, assessment of airway responsivenes s to AMP, rather than inflammatory parameters in induced sputum, represents a sensitive method to evaluate a dose-response relationship of an inhaled corticosteroid and may have applications in evaluating other novel inhaled corticosteroids.