Although there were apparent differences in test results, asthmatic patients with different polymorphisms of the beta2-adrenergic receptor had similar clinical responses to the combination or inhaled corticosteroid plus long-acting beta2 agonist (LABA) in a controlled trial.

There are genetically-determined variations in the beta2-receptor, with two possible amino acids (glycine, Gly, or arginine, Arg) in the 16 position; there is some evidence that patients who are B16 Arg/Arg may benefit less from LABA treatment than those who are B16 Gly/Gly and a retrospective analysis of clinical trial data appeared to confirm this. The authors of this study, therefore, aimed to clarify the implication of the polymorphism in a prospective controlled cross-over trial. Participants were patients with stable asthma who were homozygous for B16 Arg/Arg or B16 Gly/Gly; they were randomised in pairs of opposite genotype matched by clinical status. Eligible pairs were randomised to receive inhaled LABA (salmeterol) or placebo plus inhaled corticosteroid (beclomethasone) for 18 weeks, followed by treatment crossover for a further 18 weeks. Primary outcome was morning peak expiratory flow (PEF); secondary outcomes included airway responsiveness by inhaled methacholine challenge.

In both B16 Arg/Arg and B16 Gly/Gly participants, at 18 weeks the morning PEF was higher in the LABA group than the placebo group: difference 21.4 L/min (95% CI 11.8 to 31.1) in those who were Arg/Arg, and 21.5 L/min (95% CI, 11.0 to 32.1) in those who were Gly/Gly (both p<0.0001); difference between Arg/Arg and Gly/Gly -0.1 L/min (95% CI, −14.4 to 14.2; p=0.99).

In one of the pre-specified secondary outcomes, airways responsiveness by methacholine challenge, there was a difference in response. In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p<0.0001), whereas in Arg/Arg participants there was no significant difference between LABA and placebo recipients.

There were no significant differences between the groups in asthma exacerbations, or in severe adverse events, and none of the severe adverse events that occurred were considered to be disease or treatment related.

The authors conclude that in this study, patients with asthma and receiving inhaled corticosteroid had a similar clinical response to LABA irrespective of B16 genotype. Further research is needed to identify the significance of the difference in response to methacholine, however the practical implication of their research is that any patient with asthma who would be eligible for LABA plus inhaled corticosteroid treatment should receive it.

An accompanying Comment discusses the study: the author briefly notes the preceding research in the field, and summarises some of the questions answered and still unanswered by this well-conducted trial.