title: Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics.
abstract: 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 O(3) at 2-week intervals. Apocynin (3 ml of 0.5 mg/ml) was inhaled 2 times before and 6 times after O(3) exposure at hourly intervals. At 36 h before and 16 h after O(3) exposure, methacholine inhalation challenge tests (Mch) were performed, and PC(20) and maximal % fall from baseline (MFEV(1)) were calculated from dose-response curves. O(3)-induced change in PC(20) (Delta PC(20)) 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). O(3)-induced Delta MFEV(1) was 11.9 +/- 1.5% (p =.008) during placebo inhalation and 3.85 +/- 1.8% during apocynin (p =.47). Apocynin reduced the Delta MFEV(1) by 8.05% compared to placebo (p =.025). We conclude that apocynin markedly reduced O(3)-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.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, The, Leiden, Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Peters
authors.forename: J T
authors.initials: JT
authors.lastname: Hiltermann
authors.forename: J
authors.initials: J
authors.lastname: Stolk
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010126:Ozone; D010919:Placebos
chemical_list: D000098:Acetophenones; D000336:Aerosols; D000975:Antioxidants; D016085:Bronchoconstrictor Agents; D004791:Enzyme Inhibitors; D010919:Placebos; D016210:Methacholine Chloride; D010126:Ozone; C056165:acetovanillone; D019255:NADPH Oxidases