Child asthma pumps questioned

According to several newspapers, the inhaled drug Ventolin may not work for one in ten children with asthma.

The reports come following a study of over 1,000 young people with asthma, which found that those who had one or more copies of the Arg16 gene had an increased risk of acute severe asthma episodes if they used the short-acting salbutamol inhaler (marketed as Ventolin), or the long-acting drug salmeterol, on a daily basis.

However, people with asthma should not be overly concerned by the recent media reports and should not stop taking their short-acting bronchodilator drugs, such as salbutamol, which remain essential in treating acute asthma attacks. As a lead author of the study said, “Do not stop using your inhaler or change the way you use the inhalers.” People with asthma should consult their doctor if they find they need to use short-acting relieving inhalers such as Ventolin every day, or if their asthma is worsening after being prescribed a bronchodilator such as salmeterol (Serevent).

This important research shows that a genetic test for Arg 16, not currently available, requires further study into whether it might have a clinical role in predicting future asthma attacks.

Where did the story come from?

Dr Kaninika Basu and colleagues from UK medical institutions carried out this research, which was published in the Journal of Allergy and Clinical Immunology. Funding was received from the Gannochy Trust, Scottish Enterprises Tayside and the Perth and Kinross Council.

What kind of scientific study was this?

This was a cohort study looking at the prevalence of certain genes in 1182 Scottish people with mild, persistent asthma. These participants ranged in age from three to 22 years old.

The purpose of the study was to see whether a particular allele (an alternative form of a gene on a certain chromosome) seems to predispose people to acute episodes of asthma. Prior research has shown that the Arg16 allele of the ADRB2 gene increases this predisposition, and the researchers wanted to examine how this may be affected by the daily use of long-acting bronchodilator drugs, which are inhaled to open the airways.

The participants used a mouthwash to provide a DNA sample. This was analysed to see if they had either the Arg or Gly alleles at position 16 on the ADRB2 gene. The researchers took a detailed medical history for each participant and asked about asthma medication use, absence from school and hospital admission in the past six months. The participants’ lung function was then tested.

What were the results of the study?

Out of 1182 people, 43.8% were heterozygotes, which means that they had one copy of the Arg allele and one copy of the Gly allele at position 16 (Arg/Gly16). The remainder of the participants were homozygotes, which means that they had two copies of the same allele: 40.8% had two copies of the Gly allele (Gly/Gly16) and 15.3% had two copies of the Arg allele (Arg/Arg16).

The researchers found that for each copy of the Arg16 allele that an asthmatic person had, they were 30% more likely to have episodes of acute severe worsening of their asthma, medically known as exacerbations. (Odds Ratio 1.30, 95% Confidence Interval 1.09 to 1.55)

However, the increased risk with the ARG16 allele was mostly associated with the use of daily inhaled short-acting bronchodilators (such as salbutamol/Ventolin) or long-acting bronchodilators (salmeterol/Serevent). People who used these drugs and possessed the allele had a 64% increased risk of exacerbations (OR 1.64, 95% CI 1.22 to 2.20). This risk increase was not seen in those using inhaled bronchodilators less than once a day.

What interpretations did the researchers draw from these results?

The researchers conclude that asthmatic children and young adults with the Arg16 form of the ADRB2 gene have increased risk of asthma exacerbations if they use daily inhaled bronchodilators, regardless of whether they are short or long-acting formulations.

What does the NHS Knowledge Service make of this study?

This study is of value given the high prevalence of asthma and the universal use of bronchodilators in the management of asthma. These inhaled drugs are initially prescribed for use only when asthma becomes bad (as-required prescription rather than regular use), but if the condition is not controlled, inhaled corticosteroids may be prescribed. If further treatment is necessary, longer-acting bronchodilators may be prescribed.

Given the widespread use of bronchodilators by both adults and children, reports on this study could potentially alarm people. While this concern is understandable, this is initial research and short-acting inhalers are still the best treatments for asthma attacks. As one of the lead authors of the study, Professor Mukhopadhyay, has emphasised, “Do not stop using your inhaler or change the way you use the inhalers."

The bottom line is that, although this is very important research into an area that requires further examination, people should not be overly concerned by news reports and should not withdraw from short-acting bronchodilator drugs such as salbutamol (Ventolin), which remain very important drugs in the reversal of an acute asthma attack.

If a person finds they need to use this inhaler on a daily basis then they should consult their doctor, as it is likely that they require more effective management. If a person has more severe asthma and has been prescribed a long-acting daily bronchodilator such as salmeterol (Serevent) and their asthma is worsening, then they should also consult their doctor as this medication may need to be removed.

There are several aspects of this study that should also be considered when interpreting its results:

• During an episode of asthma, a person’s airways become constricted, restricting the airflow in and out of the lungs. Although regular inhaled corticosteroids reduce inflammation of the airways and help to prevent episodes of asthma, short-acting bronchodilators, such as salbutamol (the blue inhaler), can rapidly reverse the symptoms of an asthma attack. Therefore they still remain very effective and necessary asthma drugs.
• UK guidelines suggest that long-acting bronchodilators should only be considered as a third step, when short-acting bronchodilators and inhaled steroids alone do not control asthma. At this stage, the asthma should be quite closely monitored and managed by a doctor.
• Certain information on hospital admission, school absence or use of oral steroids for asthma was collected using yes/no answers, which may not provide a sufficient level of detail to draw conclusions with.
• The increased risk of exacerbations with the Arg16 genotype was not associated with increased risk of hospitalisation. Furthermore, as one of the measures of an exacerbation was taken to be school absence due to asthma, this gives no indication of the severity of the episode.
• One of the first signs of worsening asthma is an increasing reliance on Ventolin; therefore it is not surprising that children who had more exacerbations also used more Ventolin. This is likely to be because they used more Ventolin due to having regular exacerbations, not because the Ventolin was actually causing the exacerbations.
• The researchers have stated in their press release that much more research will be needed to determine if genetic testing for the Arg16 variant should be used when deciding routine asthma prescribing.