Actions other than smooth muscle relaxation may play a role in the protective effects of formoterol on the allergen-induced late asthmatic reaction

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® Aerolizer™, 24 μg 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 32 h. 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 5 h (all P ≤ 0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32 h after allergen inhalation (all P ≤ 0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5 h and between 7 and 28 h 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.