REPEATED INHALATION CHALLENGE WITH EXOGENOUS AND ENDOGENOUS HISTAMINE RELEASED BY ACETALDEHYDE INHALATION IN ASTHMATIC-PATIENTS

We previously reported that inhaled acetaldehyde, a metabolite of ethanol and a main factor in alcohol-induced asthma, causes bronchoconstriction indirectly through endogenously released histamine in asthmatic subjects. No study has examined the difference between tachyphylaxis in response to endogenous as opposed to exogenous histamine. Therefore, we examined tachyphylaxis occurring in response to repeated inhalation of histamine or acetaldehyde in nine asthmatic subjects. The mean acetaldehyde concentration causing a 20% decrease in FEV(1) increased significantly from 18.4 (geometric standard error of the mean (GSEM = 0.14) to 45.2 (GSEM = 0.14) mg/ml over a period of 1 h (p < 0.002), whereas the mean histamine concentrations causing a 20% decrease in FEV(1) were identical. No correlations were observed between the change in bronchial responsiveness to each solution and the change in baseline FEV(1). These results suggest that tachyphylaxis in response to histamine is observed only when the latter is released endogenously. We believe that this is the first report suggesting tachyphylaxis caused by endogenous histamine.