Study objectives: To compare the efficacy, safety, and
effects on sleep quality of salmeterol and extended-release
theophylline in patients with nocturnal asthma.
Design: Randomized, double-blind, double-dummy,
Setting: Outpatients at a
single center. Patients spent 1 night during screening and 2 nights
during each study period in a sleep laboratory for completion of sleep
Patients: Male and female patients who were
at least 18 years old with nocturnal asthma (baseline FEV1,
50 to 90% of predicted) and who required regular bronchodilator
therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil
were allowed into the study if their dosing remained constant
throughout the study.
salmeterol (42 μg per actuation), extended-release oral theophylline
(titrated to serum levels of 10 to 20 μg/mL), and placebo taken twice
Measurements and results: Efficacy measurements
included nocturnal spirometry, nocturnal polysomnography, sleep
questionnaires, and daily measurements of lung function and symptoms.
Salmeterol was superior to theophylline (p ≤ 0.05) in maintaining
nocturnal FEV1 levels and was superior to placebo
(p ≤ 0.05) in improving morning and evening peak expiratory flow
(PEF) and in decreasing nighttime albuterol use. The use of
salmeterol significantly increased the percentage of days and nights
with no albuterol use and decreased daytime albuterol use compared with
theophylline and placebo (p ≤ 0.05). Sleep quality global scores
significantly improved with salmeterol and placebo (p < 0.001) but
not with theophylline. The effects on sleep architecture were similar
across treatment groups.
Conclusions: Salmeterol (but
not theophylline) was associated with sustained improvements in morning
PEF, protection from nighttime lung function deterioration, reductions
in albuterol use, and improvements in patient perceptions of sleep. No
differences were seen in polysomnographic measures of sleep