Controversies regarding long-acting β2-agonists

Abstract

This review examines the literature regarding the efficacy and safety of long-acting β2-agonists as add-on therapy to inhaled corticosteroids. The Global Initiative for Asthma (GINA) 2009 guidelines and the National Heart, Lung, and Blood Institute (NHLBI) 2007 asthma guidelines recommend adding long-acting β2-agonists to patients inadequately controlled on inhaled corticosteroids. These recommendations must be balanced against published data which demonstrate a signal of increased morbidity and mortality with use of long-acting β2-agonists. These conflicting data raise the question of whether or not there may be genotypic or phenotypic discriminators leading to disparate responses to long-acting β2-agonists. The combination of long-acting β2-agonists and inhaled corticosteroids demonstrates improvement in asthma control and exacerbation rates; however, long-acting β2-agonists are not recommended for use as monotherapy or without optimization of inhaled corticosteroid dose. Although the majority of asthmatic patients appear to benefit from the addition of long-acting β2-agonists, there are concerns that a small proportion of patients, including steroid-naïve patients and African Americans, may not obtain such benefits. Thus far, studies have not clearly demonstrated genotypic or phenotypic differences explaining the variability in response.