Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma

Background Albeit its exact pathogenesis is still ambiguous; aspirin-intole rant asthma is one of several types of asthma for which antileukotriene the rapy is useful, because it is widely accepted that bronchial over-productio n of leukotrienes may be involved in its pathogenesis. Pranlukast (8- [p-(4 -phenylbutyloxy) benzol] amino-2-(tetrazol-5-yl)-4-oxo-4H-1-benzopyran hemi hydrate), a selective cysteinyl leukotriene receptor antagonist, is now wid ely used in the treatment of asthma. Objective This study was designed to investigate the protective effect of p ranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whe ther this: protective activity is associated with a reduction in aspirin-in duced excretion of urinary LTE4 (uLTE(4)), a marker of the cysteinyl leukot riene (LT) overproduction that participates in the pathogenesis of aspirin- induced asthma. Methods We assessed the effects of pretreatment with pranlukast on bronchoc onstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who w ere in stable clinical condition and were hypersensitive to sulpyrine provo cation testing were allocated to this study. A double-blind, randomized, cr ossover design was used. uLTE4 was measured using combined reverse-phase hi gh-performance liquid chromatography (rp-HPLC)/enzyme immunoassay. Results Pranlukast protected against analgesic-induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, bu t were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showe d little effect on excretion of uLTE(4). Conclusion These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin-into lerant asthma. Pranlukast improves not only hypersensitivity to analgesic, but also bronchial hyperresponsiveness in aspirin-intolerant asthma. It is also possible that pranlukast has another anti-asthmatic effect besides tha t of a leukotriene receptor antagonist.