Clinical Investigations Respiration 2003;70:249–253 DOI: 10.1159/000072005 Effect of Zafirlukast on Methacholine and Ultrasonically Nebulized Distilled Water Challenge in Patients with Mild Asthma P. Carratù a N. Morelli b A.X. Freire a M. Pugazhenthi a S. Guerra b R. Umberger a L. Allegra b a Division of Pulmonary and Critical Care Medicine, University of Tennessee, Memphis, Tenn., USA; b Division of Pulmonary Medicine, University of Milan, IRCCS, Milan, Italy Received: June 3, 2002 Accepted after revision: December 10, 2002 Dr. P. Carratù Division of Pulmonary and Critical Care Medicine University of Tennessee Health Science Center 956 Court Ave H316, Memphis, TN 38163 (USA) Tel. +1 901 448 7727, Fax +1 901 448 7726, E-Mail pierocarratu@yahoo.com ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2003 S. Karger AG, Basel 0025–7931/03/0703–0249$19.50/0 Accessible online at: www.karger.com/res Key Words Bronchial asthma W Bonchoconstriction W Cysteinyl-leukotrienes W Zafirlukast W Methacholine W Ultrasonically nebulized distilled water Abstract Background: Bronchial asthma is a chronic inflammatory disease characterized by airway inflammation and hy- perresponsiveness due to the release of multiple media- tors, such as cysteinyl-leukotrienes (cys-LTs). Objective: Our study was designed to investigate whether oral pre- treatment 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: Four- teen non-atopic patients (8 males, 20–42 years, forced expiratory volume in 1 s (FEV 1 ) 97% SD B 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 administra- tion, according to a single-blind method. Results: We found that pretreatment with zafirlukast significantly de- creased bronchoconstriction MC (maximum FEV 1 drop –10.75% SD B 1.89, p ! 0.001) and UNDW induced (max- imum FEV 1 drop –12% SD B 0.15, p ! 0.001), while pre- treatment with placebo did not protect patients against FEV 1 drop following MC (maximum FEV 1 drop –33.22% SD B 1.42, p ! 0.001) and UNDW challenge (maximum FEV 1 drop –30.02% SD B 0.4, p ! 0.001). Conclusions: Pretreatment with zafirlukast significantly reduced bron- choconstriction against MC and UNDW challenge in indi- viduals with mild intermittent asthma, indicating that cys-LTs receptor antagonists might be useful as pre- ventive therapy in these patients population. Copyright © 2003 S. Karger AG, Basel Introduction Bronchial asthma is a chronic inflammatory disease characterized by the presence of bronchial hyperrespon- siveness to a wide variety of physical and pharmacological stimuli with synthesis of many mediators of inflamma- tion and airflow obstruction, such as cysteinyl-leuko- trienes (cys-LTs) [1]. Leukotrienes are potent bioactive lipids derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism [2]. They have been shown to impair bronchial hyperresponsiveness to methacholine (MC) or histamine in human and animal models [3, 4]. Increased levels of cys-LTs have been found in bronchoal- veolar lavage fluid of asthmatic patients following bron- chial challenges [5]. Cysteinyl-leukotriene receptor antagonists and 5-LO inhibitors partly or entirely block constrictor response to a wide range of asthma triggers, and have been recently