title: Tolerance to beta-agonists during acute bronchoconstriction.
abstract: Previous reports suggest that regular use of beta-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 microg, 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 microg 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 beta-agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled beta-agonists may lead to a reduced response to emergency beta-agonist treatment during asthma exacerbations.
authors.affiliation: Dept of Medicine, Dunedin School of Medicine, New Zealand.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hancox
authors.forename: R E
authors.initials: RE
authors.lastname: Aldridge
authors.forename: J O
authors.initials: JO
authors.lastname: Cowan
authors.forename: E M
authors.initials: EM
authors.lastname: Flannery
authors.forename: G P
authors.initials: GP
authors.lastname: Herbison
authors.forename: C R
authors.initials: CR
authors.lastname: McLachlan
authors.forename: G I
authors.initials: GI
authors.lastname: Town
authors.forename: D R
authors.initials: DR
authors.lastname: Taylor
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000402:Airway Obstruction / Q000188:drug therapy*; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013726:Terbutaline / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D019819:Budesonide; D013726:Terbutaline; D000420:Albuterol