Inhibitory effect of indomethacin on tachyphylaxis in response to acetaldehyde-induced bronchoconstriction in patients with asthma.

Abstract

Acetaldehyde, a main factor in alcohol-induced asthma, causes bronchoconstriction indirectly through histamine release; and tachyphylaxis in response to repeated inhalation of acetaldehyde is observed in patients with asthma. The study was designed to clarify the mechanism of tachyphylaxis in response to acetaldehyde-induced bronchoconstriction. We investigated the bronchial response to inhaled acetaldehyde in 10 patients with asthma who were treated with indomethacin in a double-blind, randomized, placebo-controlled, crossover fashion. The mean acetaldehyde concentration causing a 20% fall in FEV1 with placebo increased significantly from 13.0 mg/ml (geometric SEM = 0.115) to 31.1 mg/ml (geometric SEM = 0.069) over a period of 1 hour (p < 0.01), whereas there was a slight but not significant tachyphylaxis during indomethacin treatment. The tachyphylactic effect, expressed as logarithmic value of the second PC20 minus logarithmic value of the first PC20, was significantly (p < 0.05) reduced from 0.380 (0.066) with placebo treatment to 0.148 (0.094) with indomethacin treatment. These results suggest an important role of cyclooxygenase pathway products in decreased response to repeated inhalation of acetaldehyde in patients with asthma.