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.
Medical Department TTA, State University Hospital, Copenhagen, Denmark.
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Frølund
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Madsen
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Nielsen
D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists; D008168:Lung / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011804:Quinolines; D015203:Reproducibility of Results; D013189:SRS-A / Q000037:antagonists & inhibitors*
D020024:Leukotriene Antagonists; D011804:Quinolines; D013189:SRS-A; C059177:SR 2640