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

Richard R Rosenthal, William W. Busse, James P. Kemp, James W. Baker, Christopher Kalberg, Amanda Emmett, Kathleen A. Rickard

Research output: Contribution to journalArticle

Abstract

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 ≥ 12 years of age with baseline FEV1 of ≥ 70% of predicted values. Patients were not using inhaled corticosteroids. Interventions: Twice-daily salmeterol aerosol, 42 μg, 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 β-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.

Original languageEnglish (US)
Pages (from-to)595-602
Number of pages8
JournalChest
Volume116
Issue number3
DOIs
StatePublished - 1999

Fingerprint

Albuterol
Placebos
Methacholine Chloride
Asthma
Aerosols
Therapeutics
Salmeterol Xinafoate
Metered Dose Inhalers
Withholding Treatment
Bronchoconstriction
Premedication
Respiratory Function Tests
Multicenter Studies
Adrenal Cortex Hormones

Keywords

  • Asthma
  • Bronchial hyperresponsiveness
  • Methacholine challenge
  • Salmeterol

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Rosenthal, R. R., Busse, W. W., Kemp, J. P., Baker, J. W., Kalberg, C., Emmett, A., & Rickard, K. A. (1999). Effect of long-term salmeterol therapy compared with As-needed albuterol use on airway hyperresponsiveness. Chest, 116(3), 595-602. https://doi.org/10.1378/chest.116.3.595

Effect of long-term salmeterol therapy compared with As-needed albuterol use on airway hyperresponsiveness. / Rosenthal, Richard R; Busse, William W.; Kemp, James P.; Baker, James W.; Kalberg, Christopher; Emmett, Amanda; Rickard, Kathleen A.

In: Chest, Vol. 116, No. 3, 1999, p. 595-602.

Research output: Contribution to journalArticle

Rosenthal, RR, Busse, WW, Kemp, JP, Baker, JW, Kalberg, C, Emmett, A & Rickard, KA 1999, 'Effect of long-term salmeterol therapy compared with As-needed albuterol use on airway hyperresponsiveness', Chest, vol. 116, no. 3, pp. 595-602. https://doi.org/10.1378/chest.116.3.595
Rosenthal, Richard R ; Busse, William W. ; Kemp, James P. ; Baker, James W. ; Kalberg, Christopher ; Emmett, Amanda ; Rickard, Kathleen A. / Effect of long-term salmeterol therapy compared with As-needed albuterol use on airway hyperresponsiveness. In: Chest. 1999 ; Vol. 116, No. 3. pp. 595-602.
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