title: Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma.
abstract: BACKGROUND
  Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyperresponsiveness, eosinophilic inflammation and a cough response to bronchodilators. Leukotriene receptor antagonists (LTRAs) are antiasthma medications with anti-inflammatory and bronchodilatory properties. Although LTRAs exert antitussive effects in CVA, the mechanisms involved are unknown.
  
  
  OBJECTIVE
  This study aimed to clarify the antitussive mechanisms of LTRAs in CVA patients.
  
  
  METHODS
  We prospectively observed the effect of montelukast (10 mg) daily for 4 weeks in 23 consecutive nonsmoking adults with anti-inflammatory treatment-naive CVA. We evaluated, before and after treatment, the cough visual analogue scale (VAS), pulmonary function (spirometry and impulse oscillation), methacholine airway responsiveness, cough receptor sensitivity, expressed by the concentration of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs, sputum eosinophil counts and levels of inflammatory mediators, including cysteinyl leukotrienes, leukotriene B(4), prostaglandin (PG) D(2), PGE(2), PGF(2)(α) and thromboxane B(2). We compared the baseline characteristics of the patients based on the symptomatic response to montelukast, defined as a decrease in the cough VAS of >25% (n = 15) or ≤25% (n = 8).
  
  
  RESULTS
  Montelukast significantly decreased the cough VAS (p = 0.0008), sputum eosinophil count (p = 0.013) and cough sensitivity (C2: p = 0.007; C5: p = 0.039), whereas pulmonary function, airway responsiveness and sputum mediator levels remained unchanged. Multivariate analysis showed that a better response to montelukast was associated solely with younger age (p = 0.032).
  
  
  CONCLUSIONS
  The antitussive effect of montelukast in CVA may be attributed to the attenuation of eosinophilic inflammation rather than its bronchodilatory properties.
authors.affiliation: Departments of Respiratory Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takemura
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ueda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Makiko
authors.initials: M
authors.lastname: Jinnai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D015331:Cohort Studies; D003371:Cough / Q000150:complications / Q000188:drug therapy*; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D016014:Linear Models; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D011804:Quinolines / Q000008:administration & dosage*; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D016210:Methacholine Chloride; C093875:montelukast