Fox 1999

Methods	Dual‐centre double‐blind randomised controlled trial comparing budesonide 200 µg or 1 puff twice daily (via metered dose inhaler (MDI) with modified spacer and mask) versus placebo in infants admitted to hospital with acute bronchiolitis At baseline participants had a medical history, nasopharyngeal swab and clinical examination performed Randomisation occurred when infants were considered ready for discharge. Method of sequence generation and allocation concealment not described
Participants	60 infants, aged median (range) 11 (1 to 42) weeks, with clinical diagnosis of acute viral bronchiolitis requiring hospital admission were included. There were no significant differences in any patient characteristics between the 2 groups Inclusion criteria: infants aged less than 12 completed months with a clinical diagnosis of acute viral bronchiolitis Exclusion criteria: children with underlying cardiopulmonary disease, including congenital heart disease, bronchopulmonary disease and cystic fibrosis, and those who experienced respiratory problems in the neonatal period, or required mechanical ventilation during current illness Follow‐up data at 1 month were available for 54 of the 60 infants initially randomised. Budesonide group N = 26 (20 males), placebo group N = 28 (14 males) 1 participant was excluded after randomisation but before receiving any study medication as required mechanical ventilation, 1 participant was excluded at the first follow‐up appointment due to poor compliance, and 4 additional participants failed to attend any follow‐up appointments 8 included infants had been born prematurely between 32 and 37 weeks' gestation, with 6 randomised to the placebo group; however, the difference between groups was non‐significant
Interventions	Treatment group received inhaled budesonide 200 µg or 1 puff twice daily (via MDI with spacer and mask) for 8 weeks, versus placebo control group Additional medications received by participants during the next 12‐month follow‐up period included cough suppressants, oral and inhaled bronchodilators, and inhaled and systemic corticosteroids.
Outcomes	Primary outcome: reduction in incidence of coughing and wheezing episodes requiring treatment by a general practitioner (GP) or emergency department during a 12‐month follow‐up period Parent‐completed diary card record of respiratory symptoms (episodes of coughing and wheezing), GP and hospital visits, and medication prescribed and used over a 12‐month follow‐up period Clinical examinations occurred at 1, 2, 6 and 12 months post discharge. 2 adverse events were recorded; however, these were unrelated to study medication. 1 infant was admitted to hospital with viral gastroenteritis and 1 infant was re‐admitted with mild coughing and wheezing
Notes	Only episodes of cough and wheeze that required treatment by a GP or emergency department were included in the statistical analysis Written communication with the author did not provide further differentiated cough symptom data Study funded by grants from the National Asthma Campaign and The St Thomas's Hospital Special Trustees
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised to receive either budesonide or placebo (30 to each group). Method of sequence generation not described
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Stated double blind
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Unclear who was the assessor
Incomplete outcome data (attrition bias) All outcomes	High risk	Reasons for withdrawals and missing data described; however, not included in final analysis
Selective reporting (reporting bias)	Low risk	Limitations of study discussed. Authors suggested possible Type 1 error due to more males in the treatment group
Other bias	Unclear risk	Possible selection bias in recruitment, as number of potentially eligible participants not described. Additional medications allowed during the follow‐up period included inhaled and systemic corticosteroids