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 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.
Peters
E A
EA
Department of Pulmonology, Leiden University Medical Center, The, Leiden, Netherlands.
Hiltermann
J T
JT
Stolk
J
J
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
D000098:Acetophenones; D000336:Aerosols; D000975:Antioxidants; D016085:Bronchoconstrictor Agents; D004791:Enzyme Inhibitors; D010919:Placebos; D016210:Methacholine Chloride; D010126:Ozone; C056165:acetovanillone; D019255:NADPH Oxidases