Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics

Apocynin is an inhibitor of NADPH oxidase present in inflammatory cells such as eosinophils and neutrophils. We investigated the effect of inhaled apocynin on ozone-induced bronchial hyperresponsiveness in vivo. Seven mild atopic asthmatics participated in a placebo-controlled, cross-over study with two exposures to O3 at 2-week intervals. Apocynin (3 ml of 0.5 mg/ml) was inhaled 2 times before and 6 times after O3 exposure at hourly intervals. At 36 h before and 16 h after O3 exposure, methacholine inhalation challenge tests (Mch) were performed, and PC20 and maximal % fall from baseline (MFEV1) were calculated from dose-response curves. O3-induced change in PC20 (ΔPC20) after placebo treatment was −1.94 ± 0.39 DD (mean ± SEM doubling dose Mch) (p = .001) and apocynin was −0.6 ± 0.33 DD (p = .17). The difference between apocynin and placebo treatment was 1.3 DD ± 0.42 (p = .02). O3-induced ΔMFEV1 was 11.9 ± 1.5% (p = .008) during placebo inhalation and 3.85 ± 1.8% during apocynin (p = .47). Apocynin reduced the ΔMFEV1 by 8.05% compared to placebo (p = .025). We conclude that apocynin markedly reduced O3-induced hyperreactivity for Mch as well as maximal airway narrowing. The results suggest that apocynin may have a role in preventing ozone-induced exacerbations of asthma.