Chest
Volume 115, Issue 6, June 1999, Pages 1525-1532
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Clinical Investigations
Sleep
Salmeterol vs Theophylline: Sleep and Efficacy Outcomes in Patients With Nocturnal Asthma

https://doi.org/10.1378/chest.115.6.1525Get rights and content

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, three-period crossover.

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 studies.

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.

Interventions

Inhaled salmeterol (42 μg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 μg/mL), and placebo taken twice daily.

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 quality.

Section snippets

Patient Population

Nonsmoking men and nonpregnant women who were ≥ 18 years of age and who had nocturnal asthma were selected for study participation. Nocturnal asthma was defined as asthma with symptoms of cough, wheezing, chest tightness, or shortness of breath causing awakenings at least two times a week on average in the 2 months prior to the initial screening visit, with the presence of a diurnal peak expiratory flow (PEF) variation of ≥ 15% on at least 3 of 10 days during the screening period. Entry

Patient Characteristics

Demographic data and characteristics of all randomized patients are summarized in Table 1. Of the 38 patients screened, 19 were randomized to study treatment after open-label theophylline titration. The 19 patients withdrawing prior to randomization did so due to failure to meet the enrollment criteria (8), theophylline titration failure (4), adverse events (2), patient decision (2), protocol violation (1), asthma exacerbation (1), and failure to return (1). One of these patients withdrew

Discussion

Clinical studies have shown salmeterol15 and theophylline18,19 to be safe and effective in treating nocturnal asthma. In a comparison of the two medications, salmeterol was superior to sustained-release theophylline in some objective measures of efficacy and was reported to be better tolerated by study patients.16 Similar results were seen in the current study, with salmeterol providing significantly greater improvements in lung function than theophylline or placebo while reducing the

References (36)

  • ML Burr et al.

    Changes in asthma prevalence: two surveys 15 years apart

    Arch Dis Child

    (1989)
  • EA Mitchell

    Increasing prevalence of asthma

    N Z Med J

    (1983)
  • JK Peat et al.

    Prevalence and severity of childhood asthma and allergic sensitization in seven climatic regions of New South Wales

    Med J Aust

    (1995)
  • T Haahtela et al.

    Prevalence of asthma in Finnish young men

    BMJ

    (1990)
  • E Norrman et al.

    High prevalence of asthma and related symptoms in teenagers in Northern Sweden

    Eur Respir J

    (1993)
  • Y Sacher et al.

    Longitudinal study on the prevalence of asthma among Israeli young adults

    Isr J Med Sci

    (1994)
  • MS Aldrich

    Impact, presentation, and diagnosis

  • MF Fitzpatrick et al.

    Sleep quality and daytime cognitive performance in nocturnal asthma [abstract]

    Thorax

    (1990)
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    This research was supported by a grant from Glaxo Wellcome Inc.

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