Research published in The Lancet has clarified the effect of a patient’s genetic make-up on their response to B2 agonists, but questions remain about the effect of genotype on how salmeterol improves a person’s response to methacholine challenge.
It had been proposed previously that people with asthma who are homozygous for arginine at the 16th amino acid position of the B2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with long-acting B2 agonists and inhaled corticosteroids than people who are homozygous for glycine in that position (B16 Gly/Gly). The authors investigated the link between genotype and response to asthma drugs.
The multicentre, randomised, double-blind placebo-controlled trial took place in the USA and was funded by the National Institutes of Health.
Researchers screened 474 adults with moderate asthma, of whom more than half were homozygous and thus eligible for the trial – 78 people were Arg/Arg and 166 people Gly/Gly. Of these, 34 and 41 people respectively completed the trial; analysis was by intention to treat.
Over the first 18-week period participants were randomised to either an inhaled long-acting B2 agonist (salmeterol 50 micrograms twice a day) or placebo, and all had open-label beclometasone 240 micrograms twice daily. Participants then switched between salmeterol and placebo for the second 18-week period, in addition to beclometasone.
Morning peak expiratory flow (PEF) was recorded by all participants.
Researchers found that PEF did not differ between the two groups of patients – with B16 Arg/Arg and B16 Gly/Gly genotypes – and they recorded very similar lung function.
However, there was a large difference between Arg/Arg and Gly/Gly patients in the effect of salmeterol on their response to a methacholine challenge. When Gly/Gly patients had had salmeterol, the dose of methacholine required to cause a 20% decline in lung function was doubled. But in Arg/Arg patients, adding salmeterol had no effect (compared with placebo) on the dose of methacholine required to reduce lung function by 20%.
The authors say: "These findings provide reassurance that, in the general population, patients should continue to be treated with long-acting B2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype."
