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Child asthma pumps questioned

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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.

It should be emphasised that 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 crucial 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 short-acting relieving inhalers such as Ventolin are needed on a daily basis 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, which is 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 increase this predisposition, and the researchers wanted to examine how this may be affected by the daily use of long-acting bronchodilator drugs which are inhale 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. Participants’ lung function was then tested.

What were the results of the study?

Out of 1182 people 43.8% were ‘heterozygotes’, meaning 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’ meaning they possessed 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 (i.e. as-required prescription rather than regular use), but if the condition is not controlled, secondly inhaled corticosteroids and thirdly, longer-acting bronchodilators may be prescribed.

Given the widespread use of bronchodilators by both adults and children, reports on this study might potentially cause some alarm. 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 stop 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 asthma should be quite closely monitored and managed by a doctor.
  • In the study 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. Also 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. i.e. a person may be using more Ventolin because they are having regular exacerbations; not that the reverse situation that Ventolin use 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.

Links to the headlines

Commonly used inhaler ‘may fail to prevent asthma attacks in children’. The Daily Telegraph, October 07 2009

Asthma inhaler may not work for many children, study shows. The Guardian, October 07 2009

Asthma inhaler ‘failing children’. BBC news, October 07 2009

New hope for children suffering from asthma. Daily Express, October 07 2009

Inhalers ‘may fail to prevent’ asthma attacks for one in 10 children, study suggests. Daily Mail, October 07 2009

Ventolin inhalers may not work for one in ten children with asthma. The Times, October 07 2009

Asthma inhaler alert for kids. The Sun, October 07 2009

Links to the science

Basu K, Palmer CNA, Tavendale R et al.Adrenergic beta-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. Allergy and Clinical Immunology, October 5 2009

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Readers' comments (1)

  • Surely this simply comes down to the well known fact that salbutamol and salmeterol are relievers and not preventers? If a patient needs to use salbutamol more than 2-3 times a week they are not well controlled and need their asthma medication reviewed as they are more likely to have an exacerbation, nothing new there. Typical of the press to print misleading banner headlines with the risk that the general public will stop using medications that can save lives. My only hope is that it may highlight to those patients who read the articals and need to use salbutamol regularly that they need to visit their asthma nurse or GP.

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