Add‐on therapy with montelukast or formoterol in patients with the glycine‐16 β2‐receptor genotype

AIMS: We assessed whether montelukast or formoterol provides additive effects to asthmatics not controlled on inhaled corticosteroids, by studying patients who were considered to be genetically susceptible to beta2-receptor down regulation and subsensitivity, and who expressed the homozygous glycine-16 beta2-receptor genotype. METHODS: Fifteen corticosteroid-treated, mild to moderate persistent asthmatics received montelukast 10 mg once daily or formoterol 9 micro g twice daily for 2 weeks, separated by a 2-week placebo run-in and washout, in a double-blind, double-dummy, randomized crossover design. Bronchoprotection against adenosine monophosphate (AMP) challenge (primary endpoint), spirometry and blood eosinophils were measured at trough after placebo, first and last doses. RESULTS: For AMP PC20vs placebo, there were sustained significant (P < 0.05) doubling dilution improvements following first (1.1; 95% CI 0.4, 1.9) and last (1.0; 95% CI 0.3, 1.8) doses of montelukast, and following first (1.3; 95% CI 0.1, 2.6) but not last (0.3; 95% CI -0.9, 1.6) doses of formoterol. Blood eosinophils (x 10(6) l(-1)) were significantly (P < 0.05) suppressed after the last dose of montelukast (-71; 95% CI -3, -140) compared with placebo, while formoterol exhibited a nonsignificant rise (20; 95% CI -92, 132). Neither treatment significantly improved FEV1, FEF25-75 or PEF after 2 weeks. CONCLUSIONS: In genetically susceptible patients with the homozygous glycine-16 genotype, montelukast, but not formoterol, conferred sustained anti-inflammatory properties in addition to inhaled corticosteroid, which were dissociated from changes in lung function after 2 weeks. Thus, assessing lung function may miss potentially beneficial anti-inflammatory effects of montelukast when used as add-on therapy.