Inhibitory Effect of a Selective Thromboxane Synthetase Inhibitor, OKY-046, on Acetaldehyde-Induced Bronchoconstriction in Asthmatic Patients

¹ From the Division of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
² From the Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan

We recently reported that inhaled acetaldehyde causes bronchoconstriction indirectly via histamine release in patients with asthma. The purpose of this study was to investigate a role of thromboxane A₂ in acetaldehydeinduced bronchoconstriction in asthmatic airways. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects who were treated with placebo or OKY-046, a selective thromboxane A₂ synthetase inhibitor, of 200 mg twice a day for 3 days, and 200 mg on the fourth day (test day) in a double-blind, randomized, placebo-controlled, crossover fashion. Percentage decreases in FEV₁ caused by 20 and 40 mg/ml of acetaldehyde inhalation were significantly (p<0.05 and p<0.01, respectively) prevented by the pretreatment with OKY-046. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV₁ (PC20-Ac-CHO) was significantly (p<0.01) greater with the OKY-046 pretreatment (72.2 [1.1] mg/ml) than with the placebo pretreatment (19.8 [1.2] mg/ml). We conclude that thromboxane A₂ is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A₂ may play an important role in endogenous histamine-induced bronchoconstriction caused by acetaldehyde in asthmatic airways. We believe that this is a first report on the interaction between endogenous histamine and thromboxane A₂ in asthmatic subjects.

Key Words: acetaldehyde • asthma • OKY-046 • thromboxane A₂

Submitted on July 27, 1993
Accepted on March 8, 1994