PRANLUKAST, A CYSTEINYL LEUKOTRIENE RECEPTOR ANTAGONIST, ATTENUATES ALLERGEN-INDUCED EARLY-PHASE AND LATE-PHASE BRONCHOCONSTRICTION AND AIRWAY HYPERRESPONSIVENESS IN ASTHMATIC SUBJECTS

Background: The cysteinyl leukotrienes (cysLTs) have been implicated i n the pathogenesis of allergen-induced airway responses. The purpose o f this study was to evaluate the effects of pretreatment with the cysL T receptor antagonist pranlukast on allergen-induced early asthmatic r esponses (EARs) and late asthmatic responses (LARs) and on allergen-in duced airway hyperresponsiveness (AHR). Methods: Ten atopic, nonsmokin g patients with mild asthma and previously demonstrated early- and lat e-phase allergen-induced asthmatic responses participated in a double- blind, placebo-controlled, cross-over study, comparing treatment with either 450 mg pranlukast given twice daily or placebo for 5.5 days, A methacholine challenge was performed before administration of medicati on, and the result was expressed as the PC20, An allergen inhalation c hallenge was performed on the morning of the fifth day of treatment 2 hours after administration of medication, Methacholine challenges were also performed 2 hours after medication on days 4 and 6 (24 hours bef ore and 24 hours after allergen administration) to examine allergen-in duced AHR. Results: Pranlukast attenuated allergen-induced early respo nses, late responses, and AHR. The mean (SEM) maximal percent fall in FEV1 from baseline during the early response was 30.0% (5.1%) during p lacebo treatment and 15.5% (3.5%) during pranlukast treatment (mean di fference, 14.5%; 95% confidence interval [CI], 5.3 to 23.7; P =.007), with a mean protection afforded by pranlukast of 48.3%. The mean maxim al percent fall in FEV1 during the late response was 34.7% (5.3%) duri ng placebo treatment and 24.0% (4.4%) during pranlukast treatment (mea n difference, 10.7%; 95% CI, 4.1 to 17.3; P =.006), with a mean protec tion afforded by pranlukast of 30.8%. The mean allergen-induced shift in PC20 was -1.76 (0.32) doubling doses during placebo treatment and - 0.38 (0.31) doubling doses during pranlukast treatment (mean differenc e, -1.38 doubling doses; 95% CI, 0.44 to 2.32; P =.012), with a mean p rotection afforded by pranlukast of 78.4%. Conclusion: These results d emonstrate that pranlukast can attenuate allergen-induced early and la te airways responses and AHR and adds further support for an important role for the cysLTs in mediating allergen-induced asthmatic responses .