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Respiratory Research

, 8:19

First Online: 06 March 2007Received: 29 June 2006Accepted: 06 March 2007

Abstract

BackgroundAsthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide.

MethodsTwo double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 μg twice daily in patients with asthma.

High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 5 mg was then administered via nebuliser and the FEV1 was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV1. Salbutamol 200 μg or ipratropium bromide 40 μg was then inhaled and the FEV1 was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV1, dose of provocational agent and FEV1 fall during the challenge procedure.

ResultsThe response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo 95% confidence 5 to 25%, p = 0.008. The response to ipratropium was unchanged.

ConclusionLong-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected.

AbbreviationsAMPadenosine 5-monophosphate

AUCarea under the curve

FEV1forced expiratory volume in one second

PD20dose of bronchoprovocational challenge agent required to produce a fall in FEV1 of 20% from baseline

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Autor: Sarah Haney - Robert J Hancox

Fuente: https://link.springer.com/



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