Behind the Headlines

Friday January 23 2009

“Children who wheeze because of a virus ‘should not be given steroids’ ” reports The Daily Telegraph. The claim is based on a trial of steroid drugs commonly given as a pill to young children suffering from wheezing. It said that steroids are commonly given to children with wheeze as the drug is known to ease the symptoms of asthma, which are similar. The newspaper said that more effective treatment needed to be found for treating asthma-free children who had wheeze.

This study found that a short course of steroids did not reduce time in hospital or symptoms in children with wheezing caused by a virus. However, most of these children did not have asthma, which does respond to steroids.

Childhood asthma is difficult to diagnose and children may present with a range of symptoms. Also, wheezing symptoms are commonly associated with a “cold”, and can occur in children with or without asthma. For children who do have asthma and who are having an acute asthma attack, steroids remain an effective treatment and should continue to be used for this purpose. There is no explicit clinical guidance for treating virally induced wheeze. In a clinical setting it may be difficult to determine whether a child presenting with breathing difficulties has asthma or not.

Where did the story come from?

This research was conducted by Dr Jayachandran Panickar and colleagues from the University of Leicester, the University of Nottingham and from Barts and the London School of Medicine and Dentistry. The work was supported by a grant from Asthma UK, and  published in the peer-reviewed New England Journal of Medicine.

What kind of scientific study was this?

This was a double-blind, randomised controlled trial comparing the effects of oral steroid treatment and placebo treatment in pre-school children hospitalised with a wheezing attack.

 
Wheezing is not uncommon in children under school age, and can often be due to asthma or a viral infection affecting the upper respiratory tract. The study states that current national guidelines recommend the use of oral corticosteroid drugs to treat pre-school children who present with virus-induced wheezing. The researchers say that the evidence for the benefits of steroids in this way is contradictory and remains controversial.

The researchers were particularly interested whether a five-day course of the steroid prednisolone  is helpful for children who have virus-induced wheezing. The study focussed on children  between 10 and 60 months. Eligible children were those seen at one of three hospitals between March 2005 and August 2007 who had a wheeze attack after showing signs (according to a physician) of a viral infection of the upper respiratory tract.

From the children meeting these criteria the researchers excluded those who:

  • had heart or lung disease,
  • had a known immunodeficiency or received immunosuppressive therapy, or
  • had currently or recently been exposed to chicken pox

This left 687 children to receive either oral prednisolone or placebo.

Children were randomly assigned to receive either treatment mixed in with a flavoured drink. The use of a flavoured drink ensured the children could not identify which treatment they received. The nurse who mixed the treatment with a flavoured drink was blinded, meaning they too were not aware of whether children were receiving an active treatment or not.
 

Children were treated according to the guidelines issued by the British Thoracic Society – for instance they were given oxygen and albuterol as required. Albuterol (also known to as salbutamol) is a bronchodilator, meaning it is used to open the airways and ease breathing.If the children remained symptomatic after albuterol inhalation, they were either transferred to a short-stay ward, a paediatric ward or continued to be treated in the emergency ward.

The researchers then collected information about the care and outcomes for the child, including:

  • length of hospitalisation,
    total amount of albuterol inhaled during hospitalisation,
  • the average symptom score (rated by the parent/guardian),
  • time taken to return to “normal”
    whether the child was hospitalised again in the month after discharge, and
  • Preschool Respiratory Assessment Measure (PRAM) a score to gauge the severity of breathing difficulties in young children.

Any adverse events were also noted. The researchers then compared these outcomes between the groups to see whether prednisolone was having any effect.

What were the results of the study?

There was no difference between the groups in terms of time to hospital discharge, number of albuterol administrations, PRAM scores, in symptoms scores (rated by parents), return to normal time or in hospitalisations a month later.

When the researchers divided the children into those who were at “high risk for asthma at school age” and those who weren’t, they still found no significant effect of prednisolone treatment on time in hospital or on symptoms and other outcomes.

There were no differences between the groups in adverse events either.

What interpretations did the researchers draw from these results?

The researchers conclude that there was no evidence from their study that oral corticosteroids reduced hospital stay or symptom severity in children presenting with viral-induced wheeze. This, they caution, suggests that prenisolone should not be given routinely to preschool children with mild-to-moderate virus-induced wheezing who go to hospital.

What does the NHS Knowledge Service make of this study?

As the researchers discuss, this study (and one prior, related study) have found no effect from the use of prednisolone for children with viral-induced wheeze. They say this conflicts with the findings from other studies. The authors go on to discuss the possible reasons for this conflict, including the study’s use of PRAM scores, which the researchers say are a valid measure of symptoms.

In their discussion  the researchers say that the majority of the children in their study did not have “classic atopic asthma phenotype”, which is asthma due to allergies and exposure to environmental allergens. They say that children who do not have this form of asthma may not respond to corticosteroids.

The researchers raise the most important shortcomings of their sampling - that a substantial number of children were eligible for the study, but their parents did not give consent.
 

The outcome of the study may have been different if it had included those children who did not participate. This is because parents may have declined based on factors such as the reasons for their child’s symptoms or the severity.
Some studies suggest that response to corticosteroids in children with viral-induced wheeze may be due to the type of virus infecting the child.
This study did not have the means to compare the response in children infected with different types of virus.

An important point in addition to these is current guidance from the British Thoracic Society and the Scottish Intercollegiate Guidelines Network (which has been updated since the 2003 edition referenced by this study) suggests that oral steroids should be prescribed in hospital for very young children with moderate to severe episodes of asthma. 

Importantly, this guidance is specific to children who have a diagnosis of asthma, and not explicitly for treatment of viral-induced wheezing in children who may or may not have asthma. The findings of this study should not impact on guidance for treating asthmatic children as the participants had post-infectious wheeze and most did not have proper “asthma”.

Also, in very young children a diagnosis of asthma is notoriously difficult due to the range of presentations. Often nocturnal cough is the only symptom of asthma, while wheezing symptoms will commonly indicate a “cold” but not necessarily asthma. 

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Doubt over child asthma tactic. BBC online, January 22 2009

Children who wheeze because of a virus 'should not be given steroids'. The Daily Telegraph, January 22 2009

Links to the science

Panickar J, Lakhanpaul M, Lambert PC et al. Oral Prednisolone for Preschool Children with Acute Virus-Induced Wheezing. NEJM, 2009 Volume 360:329-338 No 4 January 22 2009

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