Actions other than Smooth Muscle Relaxation may Play a Role in the Protective Effects of Formoterol on the Allergen-Induced Late Asthmatic Reaction

Abstract

Long-acting β2-adrenoceptor agonists attenuate the allergen-induced late asthmatic reaction. We evaluated whether other mechanisms in addition to airway smooth muscle relaxation may be implicated in this protective effect. The effects of formoterol (Foradil® AerolizerTM, 24μg dry powder) on the late asthmatic reaction were assessed by a randomised crossover factorial study in 24 patients with asthma. Four challenge/treatment combinations were tested: (A) saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D) allergen/formoterol. Formoterol and placebo were administered double blind after the last inhalation of the allergen or saline. FEV1 was measured up to 32h. The bronchodilator effect of formoterol was estimated as (B−A) and the overall protective effect as (D−C). The effect not due to bronchodilation was estimated as [(D−C)−(B−A)]/2. The bronchodilator effect of formoterol was statistically significant up to 5h (all P≤0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32h after allergen inhalation (all P≤0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5h and between 7 and 28h after allergen inhalation (all P≤0.035). Our results suggest that functional antagonism may not be the sole mechanism by which formoterol attenuates the allergen-induced late asthmatic reaction.