Elsevier

The Lancet

Volume 362, Issue 9394, 1 November 2003, Pages 1433-1438
The Lancet

Articles
Efficacy of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1–5 years: randomised controlled trial

https://doi.org/10.1016/S0140-6736(03)14685-5Get rights and content

Summary

Background

Episodic wheeze triggered by viral colds is common in children aged between 1 and 5 years (preschool viral wheeze). Most affected children are asymptomatic by age 6 years. Persistence of wheeze is associated with above-average systemic eosinophil priming. Use of parental-initiated oral prednisolone is recommended at the first sign of preschool viral wheeze. However, evidence for this treatment strategy is conflicting. We therefore aimed to assess the efficacy of a short course of oral prednisolone for preschool viral wheeze, with stratification for systemic eosinophil priming.

Methods

Children aged 1–5 years admitted to hospital with viral wheeze were allocated to either a high-primed or low-primed stratum according to amounts of serum eosinophil cationic protein and eosinophil protein X, and randomised to parent-initiated prednisolone (20 mg one daily for 5 days) or placebo for the next episode. The primary outcomes were the 7-day mean daytime and night-time respiratory symptom scores, which were analysed by mean differences between treatment groups.

Findings

108 children were randomised to placebo and 109 to prednisolone. Outcome data were available for 120 (78%) of 153 children who had a further episode of viral wheeze, of whom 51 received prednisolone and 69 placebo. Mean daytime (difference in means −0·01 [−0·22 to 0·20]) and night-time (0·10 [−0·12 to 0·32]) respiratory symptom scores and need for hospital admission did not differ between treatment groups. Within the high-primed (n=59) and low-primed (n=61) strata there was no difference in primary outcome between treatment groups.

Interpretation

There is no clear benefit of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1–5 years even in those with above-average eosinophil priming.

Introduction

The clinical diagnosis of asthma encompasses different phenotypes of wheeze associated with different risk factors, long term outcomes, underlying inflammation, and responses to treatment.1, 2, 3 The predominant asthma phenotype in school-age children (6–16 years) is the classic atopic variant; a disorder characterised by widespread airflow obstruction, increased airway responsiveness to a range of stimuli, pulmonary eosinophilia, and, in vitro, a propensity of systemic eosinophils to release eosinophil cationic protein (ECP) and eosinophil protein X (EPX).4, 5, 6, 7 By contrast, asthma in children aged 1–5 years is characterised by recurrent, transient episodes of wheeze triggered by viral colds; 8, 9 a phenotype previously labelled as wheezy bronchitis,8 and now as preschool viral wheeze.10 Although airway cells have not been examined in acute cases of this disorder, there is indirect evidence that its inflammatory substrate differs from atopic asthma. First, most children with preschool viral wheeze do not have risk factors for atopic sensitisation.11 Second, most become asymptomatic by 6 years of age.12 However, characteristic risk factors for atopic asthma, including increased systemic eosinophil priming, are associated with the few children in whom wheezing does not resolve.11 For example, Villa and colleagues,13 reported that in preschool children with episodic wheeze, increased serum ECP was associated with a subsequent diagnosis of current asthma at a 2-year follow-up.

Preschool viral wheeze is a transient condition, and is treated by inhaled bronchodilators as required. An additional strategy is to start a short course of systemic corticosteroids at the first sign of viral wheeze, with the aim of attenuating lung inflammation, and preventing progression to severe wheeze.14 Indeed, extrapolation from trials in adults and older atopic asthmatic children presenting to hospital clinicians, suggests that early use of corticosteroids should reduce attack severity.15 The consensus in the UK and the USA thus lends support to the practice of issuing parents with a course of oral steroids for treatment of viral wheeze in their young children.5, 16 However, evidence that corticosteroids given during the early stages of preschool viral wheeze improve clinical outcome is conflicting. Researchers of two placebo-controlled studies of parent-initiated treatment, that probably included young children with viral wheeze, noted that a 5-day course of oral prednisolone did not reduce respiratory symptoms.17, 18 By contrast, results of an open-label trial showed that oral prednisolone initiated by parents at the first sign of a cold resulted in a 90% reduction in admissions to hospital in preschool children with a history of recurrent severe attacks.19

In this investigation, we aimed to assess the efficacy of a parent-initiated short course of oral prednisolone in preschool viral wheeze. Stratification for systemic eosinophil priming was included to ensure that we could identify children at increased risk for atopic asthma. The primary outcomes were the 7-day mean daytime and night-time lower respiratory symptom score, obtained from a parent-completed symptom diary.

Section snippets

Patients

Children eligible for inclusion in the study were aged between 1 and 5 years of age, and were admitted with viral wheeze to the University Hospitals of Leicester NHS Trust Children's Hospital between June 1, 1999, and June 30, 2002. We defined preschool viral wheeze as an acute episode of wheeze that arose within 2 days of the onset of coryzal upper respiratory tract symptoms. Exclusion criteria were: a history of chronic lung disease, upper respiratory tract structural abnormality, substantial

Results

708 children admitted with acute lower respiratory tract symptoms underwent review by a research nurse. 345 were excluded, and 130 parents refused consent. Consent was obtained from the remaining 233 parents. A blood sample could not be taken from eight children (figure), thus 225 children with acute viral wheeze were entered into the trial: 110 in the high-primed eosinophil stratum, and 115 in the low-primed stratum (figure). Eight children were withdrawn before randomisation, and 108 were

Discussion

Our results show that, in children with a previous history of a clinically significant episode of viral wheeze, a 5-day course of oral prednisolone initiated by the parents at home at the start of wheezing did not have an effect on the daytime and night-time lower respiratory tract symptom score, need for inhaled salbutamol, or need for hospital admission. Furthermore, we did not record evidence for a beneficial effect of prednisolone in children with increased systemic eosinophil priming.

Our

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