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Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial.
Respir Res. 2005 Sep 16; 6:107.RR

Abstract

BACKGROUND

Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist.

METHODS

Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 microg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 microg (cumulative dose) was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve.

RESULTS

The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68%) lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001).

CONCLUSION

The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

Authors+Show Affiliations

Freeman Hospital, Newcastle-upon-Tyne, UK. sas_haney@yahoo.co.ukNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

16168062

Citation

Haney, Sarah, and Robert J. Hancox. "Tolerance to Bronchodilation During Treatment With Long-acting Beta-agonists, a Randomised Controlled Trial." Respiratory Research, vol. 6, 2005, p. 107.
Haney S, Hancox RJ. Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial. Respir Res. 2005;6:107.
Haney, S., & Hancox, R. J. (2005). Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial. Respiratory Research, 6, 107.
Haney S, Hancox RJ. Tolerance to Bronchodilation During Treatment With Long-acting Beta-agonists, a Randomised Controlled Trial. Respir Res. 2005 Sep 16;6:107. PubMed PMID: 16168062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial. AU - Haney,Sarah, AU - Hancox,Robert J, Y1 - 2005/09/16/ PY - 2005/04/15/received PY - 2005/09/16/accepted PY - 2005/9/20/pubmed PY - 2006/3/30/medline PY - 2005/9/20/entrez SP - 107 EP - 107 JF - Respiratory research JO - Respir. Res. VL - 6 N2 - BACKGROUND: Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. METHODS: Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 microg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 microg (cumulative dose) was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. RESULTS: The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68%) lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001). CONCLUSION: The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/16168062/Tolerance_to_bronchodilation_during_treatment_with_long_acting_beta_agonists_a_randomised_controlled_trial_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-6-107 DB - PRIME DP - Unbound Medicine ER -