Pranlukast, a cysteinyl leukotriene receptor antagonist, attenuates allergen-induced early- and late-phase bronchoconstriction and airway hyperresponsiveness in asthmatic subjects

Abstract

Background: The cysteinyl leukotrienes (cysLTs) have been implicated in the pathogenesis of allergen-induced airway responses. The purpose of this study was to evaluate the effects of pretreatment with the cysLT receptor antagonist pranlukast on allergen-induced early asthmatic responses (EARs) and late asthmatic responses (LARs) and on allergen-induced airway hyperresponsiveness (AHR).

Methods: Ten atopic, nonsmoking patients with mild asthma and previously demonstrated early- and late-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 medication, and the result was expressed as the PC20. An allergen inhalation challenge 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 before and 24 hours after allergen administration) to examine allergen-induced AHR.

Results: Pranlukast attenuated allergen-induced early responses, late responses, and AHR. The mean (SEM) maximal percent fall in FEV1 from baseline during the early response was 30.0% (5.1%) during placebo treatment and 15.5% (3.5%) during pranlukast treatment (mean difference, 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 maximal percent fall in FEV1 during the late response was 34.7% (5.3%) during placebo treatment and 24.0% (4.4%) during pranlukast treatment (mean difference, 10.7%; 95% CI, 4.1 to 17.3; P = .006), with a mean protection 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 difference, -1.38 doubling doses; 95% CI, 0.44 to 2.32; P = .012), with a mean protection afforded by pranlukast of 78.4%.

Conclusion: These results demonstrate that pranlukast can attenuate allergen-induced early and late airways responses and AHR and adds further support for an important role for the cysLTs in mediating allergen-induced asthmatic responses.