Additive Bronchoprotective and Bronchodilator Effects With Single Doses of Salmeterol and Montelukast in Asthmatic Patients Receiving Inhaled Corticosteroids

• DOI: 10.1378/chest.117.4.950
• Publication Date: 2003-06-13T20:09:19Z
• Authors: Owen J. Dempsey; Andrew M. Wilson; Erika J. Sims; Catrina Mistry; Brian J. Lipworth
• Keywords: Salmeterol; Bronchodilatation; Crossover study

We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting beta(2)-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation, in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone.Twelve asthmatic patients were enrolled into a single-blind, placebo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML(10)); (2) inhaled salmeterol alone, 50 microg (SM(50)); (3) ML(10) and SM(50); (4) ML(10) and inhaled salmeterol, 100 microg (SM(100)); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of >/= 20% in FEV(1) [PC(20)]) as the primary end point, and spirometry, following single doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively).Compared to placebo, all active treatments led to significant improvements (p < 0.05) in geometric mean AMP-PC(20): placebo, 42 mg/mL; ML(10), 106 mg/mL; SM(50), 115 mg/mL; ML(10) and SM(50), 183 mg/mL; and ML(10) and SM(100), 247 mg/mL. The effects of montelukast and salmeterol were numerically additive, with ML(10) and SM(100) being significantly different (p < 0.05) from ML(10) alone. For mean FEV(1) and forced expiratory flow rate between 25% and 75% of vital capacity, there were significant differences (p < 0.05) between both combination therapies vs ML(10) alone.Our results suggest additive benefits of a single dose of a long-acting beta(2)-agonist and leukotriene antagonist, in terms of bronchoprotection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.