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 inhale d corticosteroid therapy. Interventions: Montelukast, 10 mg once daily, or salmeterol, 50 mug bid, ea ch for 2 weeks with 1-week run-in and washout placebo periods. Measurements and results: Adenosine monophosphate (AMP) bronchial challenge, blood eosi nophil count (EOS), exhaled nitric oxide, and lung function after both plac ebo periods and after the first and last doses of each active treatment. Pa tients recorded their domiciliary peak expiratory flow (PEF), asthma sympto ms, and rescue bronchodilator requirement (RES) twice daily throughout the study. For the primary end point of the provocative concentration of AMP ca using a 20% fall in FEV1, 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 +/- 134.5 mg/mL) but not the last (70.1 +/- 23.7 mg/mL) dose of salmeterol, On ly montelukast produced significant suppression of the EOS. Neither drug af fected exhaled nitric oxide levels. There were significant improvements wit h the first doses of salmeterol for all parameters of lung function. After 2 weeks of treatment, there were significant improvements with both drugs f or 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 produ ced significant effects on AMP challenge and EOS suggesting anti-inflammato ry activity.