Treating children with asthma according to their genetic profile could help improve the efficacy of their medication, suggest results from a UK study.
It is known that as many as one in seven children with asthma have a specific variant in the ADRB2 gene that triggers a poor response to long-acting beta-2 agonist medication, such as salmeterol. This gene encodes the beta-2 adrenergic receptor, which is the target of many asthma drugs.
This kind of medication is normally given alongside shorter acting anti-exacerbation drugs such as salbutamol, which also target the beta-2 adrenergic receptor. Drugs like salmeterol are normally helpful at preventing asthma attacks, but in children with the ADRB2 variant it can make their asthma worse.
“Asthma is a common condition in children that causes coughing, wheezing and difficulty breathing. In the UK, for example, asthma affects one in 11 children and every 18 minutes a child is admitted to hospital because of their asthma,” explained Tom Ruffles, MD, a pediatric respiratory physician based at the Royal Alexandra Children’s Hospital in the UK, one of the lead researchers on this study.
“We have a number of medicines that are generally effective in treating children with asthma, but they don’t work equally well for all children. We think that genetic differences could have an effect on whether these medicines work, and that’s what we wanted to examine in this study.”
Ruffles worked with Somnath Mukhopadhyay, MD, a professor of pediatrics, based at the Brighton and Sussex Medical School, UK, and other colleagues on the trial, which included 241 children with asthma, aged 12-18 years, who were randomized to receive either normal treatment or treatment according to their genotype.
The children assigned to the personalized treatment group were all tested to find out their ADRB2 genotype. If they were found to have the problematic variant then they were given treatment with an alternative drug called montelukast rather than salmeterol if they needed add-on medication. The children in the study were followed up for 12 months and changes in their asthma quality of life score (which scores from 1-7) were recorded.
The team found that personalized therapy significantly improved the quality of life score for the children in this group by 0.16 compared with children in the standard treatment group. These results were presented by Ruffles at the recent virtual European Respiratory Society International Congress.
The adverse effects associated with the ADRB2 variant rs1042713 are specifically linked to carriers of the A allele. The researchers found the improvement in symptoms was particularly noticeable in children who had two copies of the A allele. In this group, personalized therapy improved their quality of life score by 0.42 compared with standard treatment.
“These results are very promising because they show, for the first time, that it could be beneficial to test for certain genetic differences in children with asthma and select medication according to those differences,” said Mukhopadhyay.
“In this study, we saw only a modest effect, but this may be partly because the children’s asthma was generally very well controlled and only a few children experienced any serious symptoms during the 12-month period. Larger trials, with a focus on those with poorer asthma control, may help us determine the true benefit for children of prescribing in this way.”
Although the team acknowledges that more research is needed in this area, the results suggest that the quality of life of children with the ADRB2 variant could be improved by the use of a genetic test that costs less than $25 to complete.
