THE EFFECT OF INHALED LEUKOTRIENE-D4 IN HUMANS

Abstract

Leukotriene D4 (LTD4) is a potent bronchoconstrictor that may play an important role in asthma. The effect of LTD on human airways was characterized by normal, rhinitic, and asthmatic subjects undergoing inhalation challenge tests with LTD4 and methacholine. In all subjects increasing concentrations of LTD4 produced a parallel decrease in specific airway conductance and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (.ovrhdot.V30P). These changes occurred independent of any decrease in FEV [forced expiratory volume in 1 s], or increase in functional residual capacity. The airway response to LTD4 was maximal within 2-3 min persisted for .apprx. 30 min, and resolved over 1-3 h. Late effects were not seen. Rhinitic subjects were 3-5 times (P < 0.01) and asthmatic subjects were 25-100 times (P < 0.001) more sensitive than were normal subjects to LTD4. All 3 groups of subjects were 250-850 times more sensitive to LTD4 than to methacholine. Significant correlations were found between the concentration of LTD4 and the concentration of methacholine that produced a 35% decrease in specific airway conductance (r = 0.874; P < 0.006) and a 30% decrease in .ovrhdot.V30P (r = 0.751; P < 0.04). LTD4 is a potent bronchoconstrictor in humans, with a rapid onset of action and a prolonged effect. In contrast to previous reports, LTD4 has an equal effect on both large and small airways and that both asthmatic and normal subjects have the same degree of increased sensitivity to LTD4 as to methacholine.