Genetics, ethics, and the use of long-acting beta-adrenergics to treat asthma.

Long-acting β-agonists (LABAs) improve control of persistent asthma that is not well controlled with inhaled corticosteroids (ICS) in adults (1) and children (2), but there are safety concerns related to their continuous use (3–4). Initial pharmacogenetic studies suggested that, during long-term use of short-acting β-agonists, individuals with asthma that are homozygotes for the arginine (Arg) allele at codon 16 of the β2-adrenergic receptor gene (ADRB2) were at increased risk of adverse outcomes when compared with homozygotes for the glycine (Gly) allele or Arg/Gly heterozygotes (5, 6). Retrospective analyses of clinical trials using LABAs, either alone or in combination with ICS, revealed similar adverse outcomes in relation to the Arg/Arg genotype (7). However, other analyses of large LABA clinical trials were unable to reproduce these findings (8).