Shelley R. Salpeter, MD; Thomas M. Ormiston, MD; Edwin E. Salpeter, PhD
Acknowledgments: The authors thank Donald Miller for graphical assistance and Christopher Stave for coordinating the trials search.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Shelley R. Salpeter, MD, Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128; e-mail, email@example.com.
Current Author Addresses: Drs. S.R. Salpeter and Ormiston: Santa Clara Valley Medical Center, 751 S. Bascom Avenue, San Jose, CA 95128.
Dr. E. Salpeter: Center for Radiophysics and Space Research, 612 Space Sciences Building, Cornell University, Ithaca, NY 14853.
The regular administration of β2-agonists may be associated with the development of tolerance to their effects.
To assess the effect of regular β2-agonist use on respiratory function and β2-receptor function in asthmatic patients.
Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 to June 2003 and references of identified articles and reviews.
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.
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.
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%]).
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.
Shelley R. Salpeter, Thomas M. Ormiston, Edwin E. Salpeter. Meta-Analysis: Respiratory Tolerance to Regular β2-Agonist Use in Patients with Asthma. Ann Intern Med. 2004;140:802–813. doi: 10.7326/0003-4819-140-10-200405180-00010
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Published: Ann Intern Med. 2004;140(10):802-813.
Asthma, Pulmonary/Critical Care.
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