Objective: To assess the addition of a leukotriene
receptor antagonist and a long-acting β2-agonist as
second-line therapy in asthma.
Placebo-controlled, double-dummy, crossover study.
Setting: Outpatient clinic.
Twenty patients with persistent asthma not controlled with inhaled
Interventions: Montelukast, 10
mg once daily, or salmeterol, 50 μg bid, each for 2 weeks with 1-week
run-in and washout placebo periods.
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
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 ± 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
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.