Background: The regular administration of Î²2-agonists may be associated with the development of tolerance to their effects.
Purpose: To assess the effect of regular Î²2-agonist use on respiratory function and Î²2-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 Î²2-agonist administration in patients with asthma and did not allow â€œas-neededâ€ Î²2-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 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.
Data Synthesis: 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%]).
Conclusion: 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.