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 μg and 80 μg, 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 ciclesonide 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 μg 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 μg 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 μg, was effective in blocking all allergen-induced responses measured.

Key words: Inhaled corticosteroid, allergen inhalation, airway inflammation

Abbreviations used: AE, Adverse event, AUC_0-2h, Area under the curve of the early response, AUC_3-8h, Area under the curve of the late response, BID, Twice daily, DPI, Dry powder inhaler, EAR, Early asthmatic response;maximum % fall in FEV₁ from 0 to 2 hours after allergen challenge, ECP, Eosinophil cationic protein, ICS, Inhaled corticosteroids, LAR, Late asthmatic response;maximum % fall in FEV₁ from 3 to 8 hours after allergen challenge, MDI, Metered dose inhaler