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A dual Cys LT 1/2 antagonist attenuates allergen‐induced airway responses in subjects with mild allergic asthma
Author(s) -
Gauvreau G. M.,
Boulet L.P.,
FitzGerald J. M.,
Cockcroft D. W.,
Davis B. E.,
Leigh R.,
Tanaka M.,
Fourre J. A.,
Tanaka M.,
Nabata T.,
O'Byrne P. M.
Publication year - 2016
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12987
Subject(s) - medicine , allergen , asthma , immunology , montelukast , eosinophil , placebo , bronchospasm , sputum , allergy , airway , anesthesia , pathology , tuberculosis , alternative medicine
Background The cysteinyl leukotrienes (cys LT s) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cys LT s contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation, and mucus secretion. We tested the activity of the dual cys LT 1/2 antagonist, ONO ‐6950, against allergen‐induced airway responses. Methods Subjects with documented allergen‐induced early ( EAR ) and late asthmatic response ( LAR ) were randomized in a three‐way crossover study to receive ONO ‐6950 (200 mg) or montelukast (10 mg) or placebo q.d. on days 1–8 of the three treatment periods. Allergen was inhaled on day 7 two hours postdose, and forced expiratory volume in 1 s ( FEV 1 ) was measured for 7 h following challenge. Sputum eosinophils and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO ‐6950 vs placebo on the EAR and LAR . Results Twenty‐five nonsmoking subjects with mild allergic asthma were enrolled and 20 subjects completed all three treatment periods per protocol. ONO ‐6950 was well tolerated. Compared to placebo, ONO ‐6950 significantly attenuated the maximum % fall in FEV 1 and area under the % FEV 1 /time curve during the EAR and LAR asthmatic responses ( P < 0.05) and allergen‐induced sputum eosinophils. There were no significant differences between ONO ‐6950 and montelukast. Conclusions Attenuation of EAR , LAR , and airway inflammation is consistent with cys LT 1 blockade. Whether dual cys LT 1/2 antagonism offers additional benefit for treatment of asthma requires further study.