Turpeinen 2008.

Methods	Design: single‐centre, randomised, open‐label, parallel‐group, controlled trial Sponsor: Helsinki University Central Hospital and AstraZeneca
Participants	Setting: Helsinki University Central Hospital Eligible: 193 Randomly assigned: 59 (continuous budesonide); 58 (budesonide/placebo); 61 (disodium cromoglycate) Analysed (for growth): 52 (continuous budesonide); 46 (budesonide/placebo); 44 (disodium cromoglycate) Gender (male): 59.7% Age, years, mean (range): 6.9 (5‐10) Inclusion criteria: children 5‐10 years of age with symptoms such as wheezing, prolonged cough or shortness of breath, suggesting asthma for at least 1 month before study entry and with significant bronchial reversibility. According to symptoms and lung function tests, most children could be categorised as having mild persistent asthma Exclusion criteria: children with acute asthma; an FEV1 < 50% predicted value; treatment during preceding 2 months with ICS, cromones, leukotriene modifiers or long‐acting beta2‐agonists; total cumulative doses of previously used ICS > 36 mg, nasal corticosteroids > 12 mg or > oral doses equivalent to 200 mg prednisolone Previous regular use of ICS: cumulative doses < 36 mg
Interventions	Test group: Continuous budesonide group, receiving budesonide (400 μg twice daily for the first month, then 200 μg twice daily for 5 months) followed by low‐dose budesonide (100 μg twice daily) for 12 months Budesonide/placebo group, in which participants received identical budesonide treatment as group 1 for the first 6 months, followed by placebo for 12 months Control group: Disodium cromoglycate, in which participants received cromoglycate 10 mg 3 times daily for 18 months Budesonide was given via Turbuhaler, and cromoglycate was given via MDI. Treatment duration was 18 months
Outcomes	Number of exacerbation episodes Asthma‐free days after run‐in period Change in height over time (cm) Height was measured at each clinic visit using a stadiometer (Holtain, Crymych, UK) following a standardised procedure
Notes	For the budesonide treatment groups, treatment compliance was recorded using a home spirometer, which recorded peak inspiratory flow via Turbuhaler each time a dose of the drug was taken. In the DSCG group, the returned MDI drug canisters were counted and weighed every 3 months. Compliance rate was not reported. Mean treatment compliance for the 3 treatment groups decreased linearly from an initial level of approximately 90% to a mean level of approximately 60% towards the end of the study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Generated by a computer programme
Allocation concealment (selection bias)	Unclear risk	No details provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	High risk	Withdrawal rate was 6/59 (10.2%) in the budesonide group and 16/61 (26.2%) in the cromoglycate group
Selective reporting (reporting bias)	Low risk	Study protocol is not available, but published reports include all expected outcomes, including those that were prespecified
Other bias	Low risk	Study appears to be free of other sources of bias