Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy

Abstract

A number of lines of evidence now suggest that the bronchoactive leukotrienes, leukotriene C (LTE), LTD; and LTE, which constitute slow-reacting substance of anaphylaxis (SRS-A), may be mediators of airway narrowing in the setting of immediate hypersensitivity reactions. Normal human subjects [5] inhaled aerosols generated from solutions of LTD to determine the bronchoconstrictor potency and the time course of airway obstruction produced by this constituent of slow-reacting substance of anaphylaxis. The dose-effect and time-effect curves were compared with curves similarly generated for the well-characterized airway constrictor histamine. Leukotriene D was, on average, 5900 times more potent than histamine on a molar basis in producing an identical decrement in maximal expiratory flow rate at 30% of control vital cpacity above residual volume. Although LTD had a rapid onset of effect, similar to that of histamine, the airway obstruction produced by LTD was longer lasting, thereby reflecting more closely the response of asthmatic allergic individuals to antigen inhalation. The response of these subjects to inhalation of LTD was not altered by ingestion of aspirin, suggesting that the airway obstruction was not mediated by cyclooxygenase products of arachidonic acid.