Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids.

OBJECTIVE To assess the addition of a leukotriene receptor antagonist and a long-acting beta(2)-agonist as second-line therapy in asthma. DESIGN Placebo-controlled, double-dummy, crossover study. SETTING Outpatient clinic. PATIENTS Twenty patients with persistent asthma not controlled with inhaled corticosteroid therapy. INTERVENTIONS Montelukast 10 mg once daily, or salmeterol, 50 microg bid, each for 2 weeks with 1-week run-in and washout placebo periods. MEASUREMENTS AND RESULTS Adenosine monophosphate (AMP) bronchial challenge, blood eosinophil count (EOS), exhaled nitric oxide, and lung function after both placebo periods and after the first and last doses of each active treatment. Patients recorded their domiciliary peak expiratory flow (PEF), asthma symptoms, and rescue bronchodilator requirement (RES) twice daily throughout the study. For the primary end point of the provocative concentration of AMP causing a 20% fall in FEV(1), compared to placebo (47.5 +/- 13.0 mg/mL), there were significant differences with the first (114.1 +/- 36.9 mg/mL) and last (94.2 +/- 30.4 mg/mL) doses of montelukast as well as the first (160.1 +/- 64.5 mg/mL) but not the last (70.1 +/- 23.7 mg/mL) dose of salmeterol. Only montelukast produced significant suppression of the EOS. Neither drug affected exhaled nitric oxide levels. There were significant improvements with the first doses of salmeterol for all parameters of lung function. After 2 weeks of treatment, there were significant improvements with both drugs for RES and morning PEF. There were no significant differences between drugs for any end points except EOS. CONCLUSIONS Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy. Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity.