REPRODUCIBILITY OF LEUKOTRIENE D4 INHALATION CHALLENGE IN ASTHMATICS - EFFECT OF A NOVEL LEUKOTRIENE D4/E4-ANTAGONIST (SR-2640) ON LEUKOTRIENE D4-INDUCED BRONCHOCONSTRICTION

We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95 % confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism, furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics.