Meta-Analysis: Respiratory Tolerance to Regular β2-Agonist Use in Patients with Asthma
- Shelley R. Salpeter, MD;
- Thomas M. Ormiston, MD; and
- Edwin E. Salpeter, PhD
- From Stanford University School of Medicine, Stanford, and Santa Clara Valley Medical Center, San Jose, California; and Cornell University, Ithaca, New York.
Abstract
Background: The regular administration of β2-agonists may be associated with the development of tolerance to their effects.
Purpose: To assess the effect of regular β2-agonist use on respiratory function and β2-receptor function in asthmatic patients.
Data Sources: Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 to June 2003 and references of identified articles and reviews.
Study Selection: Randomized, placebo-controlled trials that studied at least 1 week of regular β2-agonist administration in patients with asthma and did not allow “as-needed” β2-agonist use in the placebo group.
Data Extraction: Outcomes measured in the active treatment and placebo groups were the change in FEV1 in response to treatment and subsequent β2-agonist administration, the provocative concentration of bronchoconstrictive agents causing a 20% reduction in FEV1 (PC20), and in vitro variables of leukocyte β2-receptor function.
Data Synthesis: Pooled results of 22 trials showed that regular β2-agonist use, compared with placebo, did not change the mean FEV1 after treatment or the net FEV1 treatment effect but substantially reduced the following: the peak FEV1 response to subsequent β2-agonist administration (change, −17.8% [95% CI, −27.2% to −8.5%]); the FEV1 dose response to subsequent β2-agonists (−34.8% [CI, −45.7% to −24%]); the PC20 to combined bronchoconstrictive stimuli (−26% [CI, −37% to −11%]); and leukocyte β2-receptor density (−18.3% [CI, −31.6% to −5.1%]), binding affinity (−23.1% [CI, −39.4% to −6.8%]), and in vitro response to isoproterenol (−32.7% [CI, −56.5% to −9.0%]).
Conclusion: Regular β2-agonist use for at least 1 week in patients with asthma results in tolerance to the drug's bronchodilator and nonbronchodilator effects and may be associated with poorer disease control compared with placebo.
Article and Author Information
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Acknowledgments: The authors thank Donald Miller for graphical assistance and Christopher Stave for coordinating the trials search.
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Potential Financial Conflicts of Interest: None disclosed.
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Requests for Single Reprints: Shelley R. Salpeter, MD, Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128; e-mail, salpeter{at}stanford.edu.
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Current Author Addresses: Drs. S.R. Salpeter and Ormiston: Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128.
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Dr. E. Salpeter: Center for Radiophysics and Space Research, 612 Space Sciences Building, Cornell University, Ithaca, NY 14853.
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