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 A2 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 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.
Division of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
S
S
Myou
M
M
Fujimura
K
K
Nishi
T
T
Ohka
T
T
Masuda
D000079:Acetaldehyde / Q000008:administration & dosage; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods / Q000706:statistics & numerical data; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013928:Thromboxane A2 / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014797:Vital Capacity / Q000187:drug effects
D008689:Methacrylates; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D000079:Acetaldehyde; C034364:ozagrel