INHIBITORY EFFECT OF INDOMETHACIN ON TACHYPHYLAXIS IN RESPONSE TO ACETALDEHYDE-INDUCED BRONCHOCONSTRICTION IN PATIENTS WITH ASTHMA

Background: Acetaldehyde, a main factor in alcohol-induced asthma, cau ses bronchoconstriction indirectly through histamine release; and tach yphylaxis in response to repeated inhalation of acetaldehyde is observ ed in patients with asthma. Objective: The study was designed to clari fy the mechanism of tachphylaxis in response to acetaldehyde-induced b ronchoconstriction. Methods: We investigated the bronchial response to inhaled acetaldehyde in 10 patients with asthma who were treated ,vit h indomethacin in a double-blind, randomized, placebo-controlled, cros sover fashion. Results: 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 = 0.065)) over a period of 1 hour (p < 0.01), whereas there was a slight but not signif icant tachyphylaxis during indomethacin treatment. The tachyphylactic effect, expressed as logarithmic value of the second PC20 minus logari thmic value of the first PC20, was significantly (p < 0.05) reduced fr om 0.380 (0.066) with placebo treatment to 0.148 (0.094) with indometh acin treatment. Conclusion: These results suggest an important role of cyclooxygenase pathway products in decreased response to repeated inh alation of acetaldehyde in patients with asthma.