Regular daily steroid inhalers reduce the number of severe asthma exacerbations requiring soluble tablets or injections in wheezing preschool children by about a third.
Intermittent high-dose steroid inhalers, given only when symptoms of a cold begin, were also effective for children with occasional asthma or wheezing triggered by a virus. This strategy may reduce the overall dose of steroids given to these children, though adverse effects may still occur.
Wheezing is initially treated with a β2 agonist inhaler which opens up the airways. UK guidelines recommend adding in a daily low-dose steroid inhaler if symptoms are persistent, which is in keeping with the findings of this review.
The question of whether intermittent use of steroids in pre-school children has a place in therapy has not yet been addressed by national guidance. Intermittent use would be reliant on parents being able to spot a viral illness early and able to use a more complicated inhaled steroid regimen outside of a research setting.
Why was this study needed?
Asthma is caused by inflammation of the lungs. It affects almost 1.1 million children in the UK, and more than 70 children are admitted to hospital because of asthma attacks every day. Many admissions might be avoidable with better routine care.
Wheezing is an early sign of asthma, but wheeze occurring in children alongside viral infections does not necessarily become long-term asthma. Half of children experience wheezing by six years of age, and the strategies used to prevent wheezing children from having an asthma attack vary. Steroid inhalers are sometimes used, and ways to reduce the overall dose to the lowest dose possible, are often tried because of concerns long-term treatment may retard growth. Many children under five with recurrent episodes of viral-induced wheezing or intermittent asthma end up in hospital and are given oral steroids for exacerbations or asthma attacks. This review aimed to identify the best strategy for this group of children.
What did this study do?
This was a systematic review and meta-analysis of 22 randomized controlled trials of children up to six years of age with asthma or recurrent wheeze (two or more severe episodes in the last year requiring oral or intravenous steroids). The treatments compared were daily inhaled steroids or intermittent inhaled steroids versus placebo or each other. The researchers also looked at any regimen of inhaled steroids against montelukast, a newer oral treatment for asthma. The trials lasted from six weeks to five years, though the majority were for 12 weeks.
Studies assessing the daily steroid strategy mostly used medium dosages and focused on children with persistent asthma. Studies assessing intermittent steroids used higher doses and focused on children with intermittent asthma or viral-triggered wheezing.
Most studies had a low risk of bias, so the findings are reliable. However the studies used several different inhaler delivery systems and types of steroid which may limit the generalisability of the findings.
What did it find?
- The overall rate of asthma attacks was reduced to 12.9% with the use of daily medium dose steroids, down from 24% with placebo (risk ratio [RR] 0.70; 95% confidence interval [CI] 0.61 to 0.79; 15 studies, 3278 children).
- Children with persistent asthma had fewer asthma attacks with daily steroids compared with placebo, 8.7% versus 18% (RR 0.56; 95% CI 0.46 to 0.70; eight studies, 2,505 children).
- Children with intermittent asthma or viral-triggered wheezing had fewer asthma attacks with high-dose intermittent steroids compared with placebo, 33.9% versus 51.3% (RR 0.65; 95% CI 0.51 to 0.81; five studies, 422 children).
- Only two studies directly compared daily with intermittent steroids. They showed no difference between the two strategies in the rate of severe exacerbations.
- There was not enough data available for a meta-analysis of the impact of steroids on growth rate. Four of the six studies that recorded growth showed no differences in height after one year. There was no data on the effect of inhaled steroids on the adrenal glands.
- Results for montelukast were inconclusive as both studies were judged to be at high risk of bias.
What does current guidance say on this issue?
The 2016 British Thoracic Society and Scottish Intercollegiate Guidelines Network guideline on the management of asthma recommends inhaled β2 agonists to be used as a “rescue” medicine to relieve symptoms of asthma and intermittent wheeze. Very low dose inhaled steroids should be considered for pre-school children with any of the following features, which indicate more persistent asthma: using inhaled β2 agonists three times a week or more; having symptoms three times a week or more; or waking one night a week. The lowest possible steroid dose should be used and children should have their growth monitored. Children should be treated under the care of a specialist paediatrician if on medium or higher dose steroids.
What are the implications?
This review supports current UK guidelines on the use of daily inhaled steroids as the most effective treatment for reducing the number of asthma attacks in children with persistent asthma.
The review found that pre-emptive treatment with inhaled steroids at the first suggestion of a viral infection also helped pre-school children with intermittent asthma or viral-triggered wheeze, and may reduce the overall dose of steroids. However only two studies directly compared the daily strategy versus the intermittent steroid strategy for these children. Also, in this study, there was not enough data to analyse the effect of high-dose intermittent steroids on growth rates or suppression of the adrenal glands. Nevertheless, the authors described the studies that reported growth and concluded that, overall, any growth-suppressive effects of high-dose intermittent steroids improved over time in most children. Direct comparisons of the two strategies seem to be required to clarify any implications for practice of an intermittent strategy.
Citation and Funding
Kaiser SV, Huynh T, Bacharier LB, et al. Preventing exacerbations in preschoolers with recurrent wheeze: a meta-analysis. Pediatrics. 2016;137(6);pii:e20154496.
Authors stated that no external funding was received.
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British Thoracic Society and Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. SIGN: Edinburgh; 2014.
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