Effect of zafirlukast on methacholine and ultrasonically nebulized distilled water challenge in patients with mild asthma

Background: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hyperresponsiveness due to the release of multiple mediators, such as cysteinyl-leukotrienes (cys-LTs). Objective: Our study was designed to investigate whether oral pretreatment with zafirlukast (a cys-LTs receptor antagonist) reduces bronchoconstriction against methacholine (MC) and ultrasonically nebulized distilled water (UNDW) challenge in patients with mild asthma. Methods: Fourteen non-atopic patients (8 males, 20-42 years, forced expiratory volume in 1 s (FEV₁) 97% SD ± 0.4) with mild, intermittent bronchial asthma performed a sequential weekly pulmonary function test following challenge with MC or UNDW 2 h after zafirlukast or placebo administration, according to a single-blind method. Results: We found that pretreatment with zafirlukast significantly decreased bronchoconstriction MC (maximum FEV₁ drop -10.75% SD ± 1.89, p < 0.001) and UNDW induced (maximum FEV₁ drop -12% SD ± 0.15, p < 0.001), while pre-treatment with placebo did not protect patients against FEV ₁ drop following MC (maximum FEV₁ drop -33.22% SD ± 1.42, p < 0.001) and UNDW challenge (maximum FEV₁ drop -30.02% SD ± 0.4, p < 0.001). Conclusions: Pretreatment with zafirlukast significantly reduced bronchoconstriction against MC and UNDW challenge in individuals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as preventive therapy in these patients population.