title: Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma.
abstract: BACKGROUND
  Albeit its exact pathogenesis is still ambiguous; aspirin-intolerant asthma is one of several types of asthma for which antileukotriene therapy is useful, because it is widely accepted that bronchial over-production of leukotrienes may be involved in its pathogenesis. Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-(tetrazol-5-yl)-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, is now widely used in the treatment of asthma.
  
  
  OBJECTIVE
  This study was designed to investigate the protective effect of pranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary LTE4 (uLTE4), a marker of the cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma.
  
  
  METHODS
  We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to sulpyrine provocation testing were allocated to this study. A double-blind, randomized, crossover design was used. uLTE4 was measured using combined reverse-phase high-performance liquid chromatography (rp-HPLC)/enzyme immunoassay.
  
  
  RESULTS
  Pranlukast protected against analgesic-induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, but were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showed little effect on excretion of uLTE4.
  
  
  CONCLUSIONS
  These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin-intolerant 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 that of a leukotriene receptor antagonist.
authors.affiliation: Institute for Comprehensive Medical Sciences, Fujita Health, University School of Medicine, Toyoake, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizaki
authors.forename: K
authors.initials: K
authors.lastname: Onuma
authors.forename: T
authors.initials: T
authors.lastname: Shoji
authors.forename: H
authors.initials: H
authors.lastname: Nakagawa
authors.forename: H
authors.initials: H
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: H
authors.initials: H
authors.lastname: Amayasu
mesh_terms: D000328:Adult; D000700:Analgesics / Q000009:adverse effects* / Q000276:immunology; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000276:immunology; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control* / Q000652:urine; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000517:prevention & control / Q000652:urine; D001985:Bronchial Provocation Tests; D002867:Chromones / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004177:Dipyrone / Q000009:adverse effects / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D000700:Analgesics; D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D020024:Leukotriene Antagonists; D004177:Dipyrone; D001241:Aspirin; C047681:pranlukast