Routine and inexpensive genetic testing could save a significant number of children from being given drugs that fail to help their asthma and may even make it worse, scientists say.
It is accepted that specific medicines work better on some people than on others. Drug companies are exploring the possibilities for personalised medicines: drugs targeted to an individual’s genetic makeup, which will therefore be much more effective.
But the reverse also holds true: that some drugs are likely to be ineffective and cause more side-effects in some people than in others.
A study, carried out by researchers in Brighton and Dundee among children whose asthma is poorly controlled, suggests that the drugs may be the problem in some cases. A drug called salmeterol, commonly given for the long-term control of asthma, works poorly in children with a particular genetic variant, the researchers found. As many as 150,000 children in the UK may be affected.
Professor Somnath Mukhopadhyay, from Brighton and Sussex medical school, called for new advice to be given to GPs and parents on what to do if a child fails to respond well to the drug. He suggested genetic testing should be considered for children needing these asthma drugs.
«It is a common disease affecting 1 million children in this country,» he said.
«The basic guidance should be that if the medicine is not working, the mother should contact the GP. You should not change anything until you have seen your GP. But I think the time has come to move a step further.»
The study, involving 62 children, follows earlier work by the team establishing that the genetic variant alters children’s response to asthma drugs. All the children in the study, published in the journal Clinical Science, had the genetic variant – the arginine-16 genotype of the beta-2 receptor, carried by one in seven asthma sufferers. They had all missed school, ended up in hospital or seen a GP out of hours because of asthma flare-ups.
All the children continued to use their basic inhaler for relieving symptoms, but half were randomly chosen to get salmeterol while the other half were given a different drug, montelukast.
Salmeterol is currently the preferred drug for children whose asthma cannot be controlled with inhaled steroids, because it has had the best results in large-scale asthma trials. But for this group, the difference was clear within three months: those on montelukast responded better, wheezing and coughing much less. They were less likely to experience a worsening of their symptoms and used their «reliever» inhaler less. At the start of the research, 36% of the children were using their reliever inhaler every day, but by the end of the year-long study, the numbers using it daily had halved in the montelukast group, but not in the salmeterol group.
An earlier study by the same team showed that children’s response to the common «blue» inhaler they use themselves to relieve asthma symptoms is also not as good if they have the genetic variant.
Professor Stephen Holgate, MRC clinical professor of immunopharmacology at Southampton University, said: «While genetic changes that determine bronchodilator responses in asthma have been known for some time, this is a wonderful example of stratified or personalised medicine working its way into practice. While still a small trial, the results in the asthmatic children’s response to the two treatments across a number of asthma outcomes are impressive.»
If larger trials showed the same effect, the genetic test should be made available to doctors, he said.
Malayka Rahman, from the charity Asthma UK, said the results were «really encouraging, although more research would be needed to confirm these and establish whether a genetic test for Arg16 genetic variant should be implemented. We are keen to see more research into genes that affect responses to asthma treatments across different populations, as this exciting area of research has the potential to lead to the tailoring of better treatments for an individual based on their own genetic make-up; ultimately keeping more people out of hospital and preventing unnecessary asthma deaths in the long term.»
A spokesman for GlaxoSmithKline, which makes salmeterol under the trade name Serevent, said the medicine had been extensively studied since licensing in 1990. But he added: «GSK supports ongoing research into genetics and believes this could help enhance our future understanding of how to most effectively tailor asthma treatments across different populations. The results of this small study raise interesting questions around how different patients can gain the most benefit from their medicines and it warrants further research.»
The Department of Health said asthma was increasingly being thought of as a group of conditions rather than a single disease. «By looking at specific genes in people and finding out their specific genotype, patients may, in the future, be able to use medicines that are precisely targeted to their own type of asthma,» a spokesperson said. «However, more work needs to be done before genotypes can guide the day-to-day management of asthma, in addition to the development of widespread and accessible methods for genotyping patients.»
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