LEUKOTRIENE-C4, LEUKOTRIENE-D4, AND LEUKOTRIENE-E4 ENHANCE HISTAMINE RESPONSIVENESS IN ASTHMATIC AIRWAYS

The effects of prior inhalation of each of the sulfidopeptide leukotrienes (LT), LTC4, LTD4, and LTE4 on airway responsiveness to histamine have been compared in seven asthmatic and six normal subjects. Each subject underwent histamine inhalation challenge at 1, 4, and 7 h after inhalation of phosphate-buffered saline and bronchoconstricting doses of LTC4, LTD4, LTE4, and methacholine, which produced a > 30% fall in specific airway conductance. In asthmatic subjects, prior inhalation of LTC4, LTD4, and LTE4 enhanced airway responsiveness to histamine when compared with saline inhalation, on average by a maximum of 3.9-, 2.8-, and 3.1-fold, respectively, at 4 h after inhalation. Methacholine inhalation did not significantly alter histamine responsiveness throughout the time course studied. In normal subjects, inhalation of LTC4, LTD4, LTE4, and methacholine did not change airway responsiveness to histamine. Thus, LTC4 and LTD4 were similar to LTE4 in their capacity to enhance airway responsiveness to histamine in asthmatic subjects, and, in common with LTE4, they failed to elicit a change in airway responsiveness to histamine in normal subjects.