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 language | English (US) |
|---|---|
| Pages (from-to) | 595-602 |
| Number of pages | 8 |
| Journal | Chest |
| Volume | 116 |
| Issue number | 3 |
| DOIs | |
| State | Published - 1999 |
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Keywords
- Asthma
- Bronchial hyperresponsiveness
- Methacholine challenge
- Salmeterol
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effect of long-term salmeterol therapy compared with As-needed albuterol use on airway hyperresponsiveness
AU - Rosenthal, Richard R
AU - Busse, William W.
AU - Kemp, James P.
AU - Baker, James W.
AU - Kalberg, Christopher
AU - Emmett, Amanda
AU - Rickard, Kathleen A.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Asthma
KW - Bronchial hyperresponsiveness
KW - Methacholine challenge
KW - Salmeterol
UR - http://www.scopus.com/inward/record.url?scp=0032861839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032861839&partnerID=8YFLogxK
U2 - 10.1378/chest.116.3.595
DO - 10.1378/chest.116.3.595
M3 - Article
C2 - 10492259
AN - SCOPUS:0032861839
VL - 116
SP - 595
EP - 602
JO - Chest
JF - Chest
SN - 0012-3692
IS - 3
ER -