The effect of inhaled leukotriene D₄ in humans

Leukotriene D₄ (LTD₄) is a potent bronchoconstrictor that may play an important role in asthma. To better characterize the effect of LTD₄ on human airways, normal, rhinitic, and asthmatic subjects underwent inhalation challenge tests with LTD₄ and methacholine. In all subjects increasing concentrations of LTD₄ produced a parallel decrease in specific air conductance and flow at 30% of vital capacity measured from a partial forced expiratory maneuver (V̇30P). These changes occurred independent of any decrease in FEV₁ or increase in functional residual capacity. The airway response to LTD₄ was maximal within 2 to 3 min, persisted for approximately 30 min, and resolved over 1 to 3 h. Late effects were not seen. Rhinitic subjects were 3 to 5 times (p < 0.01) and asthmatic subjects were 25 to 100 times (p < 0.001) more sensitive than were normal subjects to LTD₄. All 3 groups of subjects were 250 to 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 V̇30P (r = 0.751; p < 0.04). These results confirm that LTD₄ is a potent bronchoconstrictor in humans, with a rapid onset of action and a prolonged effect. In contrast to previous reports, we found that 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.