INHIBITORY EFFECT OF A SELECTIVE THROMBOXANE SYNTHETASE INHIBITOR, OKY-046, ON ACETALDEHYDE-INDUCED BRONCHOCONSTRICTION IN ASTHMATIC-PATIENTS

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 A(2) in acetaldehyde-induced 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 A(2) 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 FEV(1) 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-048. Geometric mean value (geometric standard error of the mean) of acetaldehyde concentration producing a 20 percent fall in FEV(1) (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 A(2) is one of contributors to acetaldehyde-induced bronchoconstriction in asthmatic subjects. It suggests that thromboxane A(2) 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 A(2) in asthmatic subjects.