B. Dahlen et al., THE LEUKOTRIENE-ANTAGONIST ICI-204,219 INHIBITS THE EARLY AIRWAY REACTION TO CUMULATIVE BRONCHIAL CHALLENGE WITH ALLERGEN IN ATOPIC ASTHMATICS, The European respiratory journal, 7(2), 1994, pp. 324-331
The hypothesis that cysteinyl-leukotrienes (LTC(4), LTD(4) and LTE(4))
are mediators of allergen-induced airway obstruction in asthmatics wa
s tested with the specific receptor antagonist ICI-204,219, in a doubl
e-blind, placebo-controlled, randomized, cross-over bronchoprovocation
study. On three occasions, cumulative bronchial challenge with specif
ic allergen was performed in 10 males with mild allergic asthma. The f
irst control session established the baseline provocative dose of alle
rgen producing a decrease in forced expiratory volume in one second (F
EV(1)) by 20% (PD(20)FEV(1)). The two rechallenges were performed 2 h
after oral administration of placebo or 20 mg of ICI-204,219. The alle
rgen dose-response relations were highly reproducible, producing PD20
values at the control session and after placebo treatment which varied
by no more than 0.7-1.3 fold (95% confidence interval(95% CI)). After
ICI-204,219, the median cumulated allergen dose was 5.5 fold higher,
and the group geometric mean PD, was increased 2.5 times. Furthermore,
the recovery time after the immediate bronchoconstriction was shorter
(40 vs 60 min). The wheal and flare responses to intradermally inject
ed LTD, were somewhat inhibited by ICI-204,219, whereas responses to h
istamine were unaffected. However, the findings suggest that skin test
ing with LTD, is unlikely to predict the degree of leukotriene-antagon
ism in the airways. The findings confirm and extend the indications th
at cysteinyl-leukotrienes are important mediators of allergen-induced
airway obstruction, and that leukotriene-antagonists should be evaluat
ed as a potential new therapy in allergic asthma.