The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma

Study objective: To determine the efficacy of salmeterol alone in a group of patients with moderate asthma with nocturnal worsening of symptoms. Design: Double-blind, randomized, placebo-controlled crossover study. Setting: Tertiary care hospital specializing in respiratory diseases. Participants: Ten patients with nocturnal asthma. Interventions: Subjects were randomized to salmeterol, 100 μg twice daily, or placebo for 6 weeks with a 1-week washout between treatment periods. Symptoms, nocturnal awakenings, and β₂-agonist use were recorded daily. Spirometry was performed at weeks 1 and 6 of each period at bedtime and at 4 AM, and methacholine challenge was performed at 4 AM followed by bronchoscopy with BAL. BAL fluid analysis included cell count and differential count, eosinophil cationic protein Charcot-Leyden crystal protein, leukotriene B₄, and thromhoxane B₂. Results: The percentage of nights with awakenings decreased significantly with salmeterol (69.8 ± 8.7% vs 30.6 ± 10.8% for placebo and salmeterol respectively p=0.02). The percentage of 24-h days with supplemental inhaled β₂-agonist use significantly decreased with salmeterol (85.9 ± 9.4% vs 70.4 ± 10.1% for placebo and salmeterol, respectively; p=0.04). There were no significant differences in bronchial reactivity, 4 AM FEV₁, overnight percentage change in FEV₁, or indexes of airway inflammation. Conclusions: Salmeterol alone improves the number of nocturnal awakenings and supplemental 24-h β₂-agonist use in nocturnal asthma without significantly altering lung function and airway inflammation.