Clinical trials for severe acute asthma in children need consistent outcome measures and large multi-centre studies

Monash University research demonstrates that large multi-centre studies with consistent outcome measures are needed to understand the management of acute severe asthma in children.

An asthma attack - where there is swelling, inflammation and muscle constriction in the air passages in the lungs - is a common reason for children to visit the emergency department. Although most children improve with first-line treatment (inhaled bronchodilators such as salbutamol (ventolin) and oral steroids such as prednisolone), some require more treatment. "We don't know which treatment is best, and what is done for children varies from hospital to hospital", said lead researcher Professor Simon Craig, Department of Paediatrics, Monash University.

Asthma is a frequent reason for a child to attend the emergency department (ED) and one of the most common reasons for paediatric hospitalization after an ED visit. In the USA, the rate of paediatric ED visits for asthma increased by 13.3% between 2001 and 2010, whilst in the UK it is estimated that a child is admitted to hospital every 20 minutes due to an asthma attack.

Speaking of the research, Professor Craig said, "There are a number of Cochrane reviews of second-line treatments for children with acute asthma. These reviews summarise the available evidence based on a rigorous analysis of randomised controlled trials. To try and provide the best information to guide emergency treatment, we set out to collate and analyse the results of all available Cochrane reviews".

"The phrase "apples and oranges" refers to the difficulty in drawing comparisons between different things. Our research has demonstrated that the existing literature is really complex, with small studies reporting many different outcomes across different patient populations and in different settings.  Rather than apples and oranges, the literature on acute asthma is more like a fruit salad!"

"Acute severe asthma is relatively rare in children. The existing evidence is based on small studies, mostly from single hospitals, and with each study using different outcomes. This makes it very hard to compare between studies".

"Our overview summarises the available evidence on acute severe asthma in children, and demonstrates that there is still a huge amount of research needed.  Future trials need to be multi-centre to be large enough to detect a treatment effect. We need to use the same outcome measures across all trials to allow us to compare different treatments".

"At this point, we need to know which treatments are most effective. Until we do this, we won't be able to impact quality of life".

The main findings (mostly based on very small studies), included:

  • intravenous magnesium sulfate appears to reduce the length of time spent in hospital;
  • no evidence suggests that any treatment reduces the risk of being admitted to intensive care;
  • some treatments appear to reduce the risk of hospital admission. These included adding ipratropium (Atrovent) to inhaled beta-agonists, giving intravenous magnesium sulfate, and breathing a mixture of helium and oxygen (Heliox);
  • serious adverse events may be reduced by inhaled magnesium sulfate;
  • nausea and/or vomiting is more common with aminophylline
  • adding ipratropium reduces the risk of nausea and tremor, but not vomiting.

Professor Craig said that this is the first time multiple Cochrane reviews on acute severe asthma in children have been brought together and hopefully this review will lay the foundation for some of this work.

Collaborators

Professor Andis Graudins (Monash University), Professor Franz Babl (Murdoch Children's Research Institute and University of Melbourne), Professor Stuart Dalziel (University of Auckland), Professor Colin Powell (Sidra Medicine, Qatar), Dr Carole Lunny (University of British Columbia, Canada)

Reference

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews Simon S Craig Stuart R Dalziel Colin VE Powell Andis Graudins Franz E Babl Carole Lunny Cochrane Database of Systematic Reviews