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

J Allergy Clin Immunol. 1997 May;99(5):620-3. doi: 10.1016/s0091-6749(97)70023-x.

Abstract

Background: 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.

Objective: The study was designed to clarify the mechanism of tachyphylaxis in response to acetaldehyde-induced bronchoconstriction.

Methods: 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.

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 = 0.069) 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.

Conclusion: These results suggest an important role of cyclooxygenase pathway products in decreased response to repeated inhalation of acetaldehyde in patients with asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetaldehyde / pharmacology*
  • Administration, Inhalation
  • Administration, Oral
  • Adult
  • Aged
  • Asthma*
  • Bronchoconstriction / physiology*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Indomethacin / pharmacology*
  • Male
  • Middle Aged
  • Tachyphylaxis / physiology*

Substances

  • Cyclooxygenase Inhibitors
  • Acetaldehyde
  • Indomethacin