Open AccessTolerance to beta‐agonists during acute bronchoconstriction
Author(s) -
Hancox R.J.,
Aldridge R.E.,
Cowan J.O.,
Flannery E.M.,
Herbison G.P.,
McLachlan C.R.,
Town G.I.,
Taylor D.R.
Publication year - 1999
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.1999.14b08.x
Subject(s) - bronchoconstriction , methacholine , bronchodilator , salbutamol , medicine , terbutaline , asthma , anesthesia , bronchodilator agents , placebo , budesonide , inhalation , respiratory disease , lung , alternative medicine , pathology
Previous reports suggest that regular use of β‐agonists does not lead to tolerance to their bronchodilator effects. However, most studies have been conducted in stable asthma. This study investigates whether bronchodilator tolerance can be demonstrated during acute bronchoconstriction. Thirty‐four asthmatic subjects were treated with 6 weeks inhaled terbutaline (1 mg q.i.d. ), budesonide (400 μg, b.i.d. ), both drugs or placebo in a randomized, double‐blind, cross‐over study. After each treatment methacholine was administered to induce a 20% fall in the forced expiratory volume in one second (FEV1). The response to inhaled salbutamol 100, 100, 200 μg at 5 min intervals) was then measured. Dose‐response curves were compared using an analysis of covariance. Pre‐methacholine FEV1, the highest pre‐methacholine FEV1, the fall in FEV1 induced by methacholine and the logarithm of the provocative dose of methacholine required to induce the 20% fall in FEV1 (PD20) were used as covariates. There was a significantly reduced response to salbutamol after 6 weeks terbutaline treatment: the mean (95% confidence intervals (CI)) area under the dose‐response curve was reduced by 36% (24, 47) compared to placebo (p<0.0001). The reduction in bronchodilator response was not affected by concomitant treatment with budesonide. Significant tolerance to the bronchodilator effect of inhaled β‐agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled β‐agonists may lead to a reduced response to emergency β‐agonist treatment during asthma exacerbations. Eur Respir J 1999; 14: 283–287.