Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy
J. W. Weiss, J. M. Drazen, E. R. McFadden Jr, P. Weller, E. J. Corey, R. A. Lewis and K. F. Austen
Five normal human subjects inhaled aerosols generated from solutions of
leukotriene D (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, 5,900 times more potent than histamine on a molar basis in
producing an identical decrement in maximal expiratory flow rate at 30% of
control vital capacity above residual volume. In addition, 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.
