Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.

Lancet
Michael E WechslerNational Heart, Lung and Blood Institute's Asthma Clinical Research Network

Abstract

Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid. In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is re...Continue Reading

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