ArticlesEfficacy of a short course of parent-initiated oral prednisolone for viral wheeze in children aged 1–5 years: randomised controlled trial
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
References (28)
- et al.
Are all wheezing disorders in very young (preschool) children increasing in prevalence?
Lancet
(2001) - et al.
Total serum IgE and its association with asthma symptoms and allergic sensitization among children
J Allergy Clin Immunol
(1999) - et al.
High levels of eosinophil cationic protein in wheezing infants predict the development of asthma
J Allergy Clin Immunol
(1997) - et al.
Tucson Children's Respiratory Study: 1980 to present
J Allergy Clin Immunol
(2003) - et al.
Adverse behavioral effects of treatment for acute exacerbation of asthma in children: a comparison of two doses of oral steroids
Chest
(2002) - et al.
Characterization of wheezing phenotypes in the first 10 years of life
Clin Exp Allergy
(2003) - et al.
Is there more than one inflammatory phenotype in asthma?
Thorax
(2002) - et al.
Clinical and biological heterogeneity in children with moderate asthma
Am J Respir Crit Care Med
(2003) - et al.
Peak flow variability, methacholine responsiveness and atopy as markers for detecting different wheezing phenotypes in childhood
Thorax
(1997) British guideline on the management of asthma
Thorax
(2003)
The relationship between airways inflammation and asthma severity
Am J Respir Crit Care Med
Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease
Clin Exp Allergy
Recurrent wheezy bronchitis and viral respiratory infections
Arch Dis Child
Episodic viral wheeze in preschool children: effect of topical nasal corticosteroid prophylaxis
Thorax
Cited by (180)
Viral Infections and Wheezing in Preschool Children
2022, Immunology and Allergy Clinics of North AmericaManagement of Asthma Exacerbations in the Emergency Department
2021, Journal of Allergy and Clinical Immunology: In PracticePrevention and treatment of recurrent viral-induced wheezing in the preschool child
2020, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Overall, no significant difference was noted in the duration of hospitalization between prednisolone-treated children (11.0 hours) and placebo (13.9 hours). The use of home-administered OCS for viral-induced wheezing was evaluated in 108 children 1 to 5 years of age.43 The children had a history of previous hospital admission for viral-induced wheezing.
Managing Chronic Cough as a Symptom in Children and Management Algorithms: CHEST Guideline and Expert Panel Report
2020, ChestCitation Excerpt :In cough associated with pertussis, dexamethasone provides no significant benefit for the symptomatic relief of cough.216 Even in children with wheeze (without asthma), one RCT in 200 children (1-5 years) found that oral steroids conferred no benefit217 but were instead associated with a non-significant increase in hospitalizations (P = .058). If a trial of asthma therapy is warranted, we suggest using 400 μg/day equivalent of budesonide or beclomethasone as this dose is effective in the management of most childhood asthma and adverse events occur on higher doses.218,219
Wheezing in children: Approaches to diagnosis and management
2019, International Journal of Pediatrics and Adolescent MedicineAdvances in the aetiology, management, and prevention of acute asthma attacks in children
2019, The Lancet Child and Adolescent Health