NIHR Signal Intermittent inhaled steroids reduce asthma attacks in wheezing preschool children

Published on 22 November 2016

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.

Intermittent inhaled steroids reduce asthma attacks in wheezing preschool children

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.

Bibliography

American Academy of Allergy Asthma and Immunology. Allergy and asthma medication guide. Milwaukee (WI): American Academy of Allergy Asthma and Immunology; 2016.

Asthma UK. Time to take action on asthma. London: Asthma UK; 2014.

Asthma UK. Asthma facts and statistics. London: Asthma UK; 2016.

British Thoracic Society and Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. SIGN: Edinburgh; 2014.

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.

Bibliography

American Academy of Allergy Asthma and Immunology. Allergy and asthma medication guide. Milwaukee (WI): American Academy of Allergy Asthma and Immunology; 2016.

Asthma UK. Time to take action on asthma. London: Asthma UK; 2014.

Asthma UK. Asthma facts and statistics. London: Asthma UK; 2016.

British Thoracic Society and Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. A national clinical guideline. SIGN: Edinburgh; 2014.

Preventing Exacerbations in Preschoolers With Recurrent Wheeze: A Meta-analysis

Published on 28 May 2016

Kaiser, S. V.,Huynh, T.,Bacharier, L. B.,Rosenthal, J. L.,Bakel, L. A.,Parkin, P. C.,Cabana, M. D.

Pediatrics , 2016

CONTEXT: Half of children experience wheezing by age 6 years, and optimal strategies for preventing severe exacerbations are not well defined. OBJECTIVE: Synthesize the evidence of the effects of daily inhaled corticosteroids (ICS), intermittent ICS, and montelukast in preventing severe exacerbations among preschool children with recurrent wheeze. DATA SOURCES: Medline (1946, 2/25/15), Embase (1947, 2/25/15), CENTRAL. STUDY SELECTION: Studies were included based on design (randomized controlled trials), population (children </=6 years with asthma or recurrent wheeze), intervention and comparison (daily ICS vs placebo, intermittent ICS vs placebo, daily ICS vs intermittent ICS, ICS vs montelukast), and outcome (exacerbations necessitating systemic steroids). DATA EXTRACTION: Completed by 2 independent reviewers. RESULTS: Twenty-two studies (N = 4550) were included. Fifteen studies (N = 3278) compared daily ICS with placebo and showed reduced exacerbations with daily medium-dose ICS (risk ratio [RR] 0.70; 95% confidence interval [CI], 0.61-0.79; NNT = 9). Subgroup analysis of children with persistent asthma showed reduced exacerbations with daily ICS compared with placebo (8 studies, N = 2505; RR 0.56; 95% CI, 0.46-0.70; NNT = 11) and daily ICS compared with montelukast (1 study, N = 202; RR 0.59; 95% CI, 0.38-0.92). Subgroup analysis of children with intermittent asthma or viral-triggered wheezing showed reduced exacerbations with preemptive high-dose intermittent ICS compared with placebo (5 studies, N = 422; RR 0.65; 95% CI, 0.51-0.81; NNT = 6). LIMITATIONS: More studies are needed that directly compare these strategies. CONCLUSIONS: There is strong evidence to support daily ICS for preventing exacerbations in preschool children with recurrent wheeze, specifically in children with persistent asthma. For preschool children with intermittent asthma or viral-triggered wheezing, there is strong evidence to support intermittent ICS for preventing exacerbations.

Children with persistent asthma were defined as having symptoms more than two days a week, night-time awakenings once to twice a month, short acting β2-agonist use (these are “rescue” medicines that mainly affect the muscles around the airways and provide quick relief of asthma symptoms) more than two days a week, or minor limitation with normal activity.

Children with intermittent asthma were defined as having symptoms on two or fewer days a week, no night-time awakenings, short acting β2-agonist use up to two days per week, and no limitation of normal activity.

An asthma attack was defined as a severe exacerbation needing treatment with systemic (oral or intravenous) steroids.

Expert commentary

This meta-analysis demonstrates the positive effect of continuous and intermittent high dose inhaled corticosteroids on exacerbations in persistent and intermittent preschool wheeze. Previous concerns surrounding the adverse effects of high dose intermittent steroids on growth are partially alleviated by two of three studies which show no difference in linear growth compared to placebo. However, additional studies using intermittent high dose steroids measuring markers of adrenal activity, over longer follow up periods, are necessary before policy is entirely changed. This analysis underscores the efficacy of steroids as first line in preschool wheeze in preventing exacerbations, but importantly suggests that intermittent high dose steroids may be safe and effective in intermittent wheeze.

Dr Cara Bossley, Consultant in Paediatric Respiratory Medicine, King's College Hospital

Expert commentary

This meta-analysis cites strong evidence for the use of intermittent inhaled steroids to treat pre-school viral-triggered wheezing. Should we adopt this practice? It might be difficult. Distinction between asthma and intermittent wheeze is not always easy in this age group and patterns of wheeze can change over time. Inhaled bronchodilators remain the treatment of choice to relieve acute wheezy symptoms. Clinicians should be aware that the addition of high doses of inhaled steroids in acute scenarios risks mixed messages about how reliever and preventer treatments work. The doses of intermittent inhaled steroids used were considerably higher than those recommended for continuous use and long term impacts on height and weight need to be clarified. Families need clear action plans for the use of bronchodilators within safe limits when treating acute wheezy episodes in primary care settings. This paediatrician does not find the arguments for routinely giving intermittent high dose inhaled corticosteroids particularly compelling.

Dr Gary Connett, Consultant Respiratory Paediatrician, Southampton Children's Hospital

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