Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness

Chest. 1999 Sep;116(3):595-602. doi: 10.1378/chest.116.3.595.


Study objectives: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge.

Design: Randomized, double-blind, placebo-controlled, multicenter study.

Setting: Thirty-one clinical centers in the United States.

Patients: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids.

Interventions: Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available.

Measurements and results: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups.

Conclusions: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage*
  • Adrenergic beta-Agonists / adverse effects
  • Adult
  • Aerosols
  • Albuterol / administration & dosage*
  • Albuterol / adverse effects
  • Albuterol / analogs & derivatives*
  • Asthma / drug therapy
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Methacholine Chloride
  • Peak Expiratory Flow Rate
  • Salmeterol Xinafoate


  • Adrenergic beta-Agonists
  • Aerosols
  • Bronchoconstrictor Agents
  • Bronchodilator Agents
  • Methacholine Chloride
  • Salmeterol Xinafoate
  • Albuterol