Antitussive Effect of the Leukotriene Receptor Antagonist Zafirlukast in Subjects with Cough-Variant Asthma*

Abstract

Cough-variant asthma (CVA) occurs in a subgroup of asthmatics whose sole or predominant respiratory symptom is cough. Although bronchodilators are often sufficient to treat CVA, refractory cough may require therapy with inhaled or systemic corticosteroids. In a randomized, double-blind, placebo-controlled, crossover study, we examined the effect of a 14-day course of the leukotriene receptor antagonist zafirlukast on subjective cough score and cough-reflex sensitivity to inhaled capsaicin in eight subjects with CVA refractory to inhaled beta agonists, and in five subjects refractory to inhaled corticosteroids. Seven of eight subjects experienced significant subjective and objective improvement in cough after treatment with zafirlukast. Mean (+/- SEM) cough score improved from 7.75 +/- 0.56 to 3.25 +/- 0.84 (p = 0.0006). Cough sensitivity to capsaicin was suppressed by zafirlukast in all subjects. Patients with CVA may represent a distinct subgroup of asthmatics whose afferent cough receptors within the respiratory epithelium are hypersensitive relative to those of patients with the typical form of asthma. Zafirlukast appears to be particularly effective in treating CVA by inhibiting the sensitivity of these receptors. Leukotriene receptor antagonists may offer an alternative to corticosteroids for the treatment of CVA refractory to inhaled bronchodilators.

Global strategy for asthma management and prevention: GINA executive summary

“…Clinical studies have demonstrated that leukotriene modifiers have a small and variable bronchodilator effect, reduce symptoms (including cough) [72], improve lung function, and reduce airway inflammation and asthma exacerbations [73][74][75]. They may be used as an alternative treatment for adult patients with mild persistent asthma [76][77][78], and some patients with aspirin-sensitive asthma respond well to leukotriene modifiers [79].…”

The diagnosis and management of chronic cough

“…A 14-day course of zafirlukast has been shown to improve cough, as well as to inhibit objectively measured cough reflex sensitivity in patients with CVA, including a subgroup whose cough had been refractory to inhaled steroids [53].…”

Clinical and Demographic Profiles of Patients Diagnosed as Cough Variant Asthma attended at Tertiary Referral Hospital

“…clinics in the world. The efficacy of a beta2-agonist for a patient's coughing is evaluated to make a diagnosis of CVA 5 . When the bronchodilator therapy is judged as efficacious, a tentative diagnosis of CVA is made.…”

“…Therefore, poorly controlled asthma remains a major problem in Bangladesh. Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyper-responsiveness, eosinophilic inflammation and a cough response to bronchodilators 5 .…”