Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

International audienc

Effect of low-dose ciclesonide on allergen-induced responses in subjects with mild allergic asthma

Background: Inhalation of allergens by sensitized patients with asthma induces reversible airway obstruction, airway hyperresponsiveness, and eosinophilic airway inflammation. Attenuation of allergen-induced bronchoconstriction and inflammation has been used to examine the efficacy of therapeutic agents such as inhaled corticosteroids in asthma. Ciclesonide, a nonhalogenated inhaled corticosteroid being developed for the treatment of persistent asthma, remains inactive until cleaved by esterases in the lung. Objective: This study examined the effect of low doses of inhaled ciclesonide, 40 Kg and 80 mu g, on allergen-induced bronchoconstriction, serum eosinophil cationic protein, and eosinophilic airway inflammation. Methods: Twenty-one nonsmokers with mild atopic asthma completed a multicenter, randomized, 3-way crossover study comparing the effects of 7-day treatment of ciclesomide or placebo. Allergen-induced responses, including the early and late fall in FEV1, peripheral blood eosinophils, serum eosinophil cationic protein levels, and eosinophils in induced sputum were measured. Results: Ciclesonide 80 jig attenuated the early and late asthmatic responses, including the change in FEV1, serum eosinophil cationic protein, and sputum eosinophils measured at 24 hours postchallenge (P <.025). Ciclesonide 40 Kg attenuated the late asthmatic responses and sputum eosinophils measured at 24 hours postchallenge (P <.025), with no effect on the early allergen-induced bronchoconstriction, 24-hour FEV1, or serum eosinophil cationic protein levels (P <.025). Conclusion: With the exception of 24-hour postchallenge peripheral blood eosinophils, a low dose of ciclesonide, 80 mu g, was effective in blocking all allergen-induced responses measured