Shelley R. Salpeter, MD; Thomas M. Ormiston, MD; Edwin E. Salpeter, PhD
The regular administration of Î²2-agonists may be associated with the development of tolerance to their effects.
To assess the effect of regular Î²2-agonist use on respiratory function and Î²2-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 Î²2-agonist administration in patients with asthma and did not allow â€œas-neededâ€ Î²2-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 Î²2-agonist administration, the provocative concentration of bronchoconstrictive agents causing a 20% reduction in FEV1 (PC20), and in vitro variables of leukocyte Î²2-receptor function.
Pooled results of 22 trials showed that regular Î²2-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 Î²2-agonist administration (change, âˆ’17.8% [95% CI, âˆ’27.2% to âˆ’8.5%]); the FEV1 dose response to subsequent Î²2-agonists (âˆ’34.8% [CI, âˆ’45.7% to âˆ’24%]); the PC20 to combined bronchoconstrictive stimuli (âˆ’26% [CI, âˆ’37% to âˆ’11%]); and leukocyte Î²2-receptor density (âˆ’18.3% [CI, âˆ’31.6% to âˆ’5.1%]), binding affinity (âˆ’23.1% [CI, âˆ’39.4% to âˆ’6.8%]), and in vitro response to isoproterenol (âˆ’32.7% [CI, âˆ’56.5% to âˆ’9.0%]).
Regular Î²2-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.
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Salpeter SR, Ormiston TM, Salpeter EE. Meta-Analysis: Respiratory Tolerance to Regular β2-Agonist Use in Patients with Asthma. Ann Intern Med. 2004;140:802-813. doi: 10.7326/0003-4819-140-10-200405180-00018
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Published: Ann Intern Med. 2004;140(10):802-813.
Asthma, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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