Baker 1999.

Methods	DESIGN: randomised, double‐blind, placebo‐controlled, parallel‐group study; multi‐centre
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 193 INTERVENTION: ICS (budesonide 250 μg/d): 94 CONTROL: ICS (budesonide 500 μg/d): 99 WITHDRAWALS: reported AGE: mean (months) (range): INTERVENTION: ICS (budesonide 250 μg/d): 54.6 (8‐107) CONTROL: ICS (budesonide 500 μg/d): 54.3 (7‐105) GENDER: N (male %): INTERVENTION: ICS (budesonide 250 μg/d): 59 (63) CONTROL: ICS (budesonide 500 μg/d): 62 (63) ASTHMA SEVERITY: moderate persistent asthma ASTHMA DURATION: mean disease duration months (range): INTERVENTION: ICS (budesonide 250 μg/d): 34.2 (2‐92) CONTROL: ICS (budesonide 500 μg/d): 32.4 (4‐96) MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: not reported ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Patients aged 6 months to 8 years with diagnosis of asthma Use of at least 1 asthma medication daily with periodic using of a rescue medication as needed for at least 3 months before visit 1 On same ICS at stable dose for at least 2 months before visit 1 Demonstrated FEV1 ≥ 50% of predicted value and 15% reversibility after a standard dose of ICS EXCLUSION CRITERIA Severe and/ or unstable asthma Long‐term use of systemic steroids within 12 weeks of visit 1 Intermittent use of systemic steroids within 30 days
Interventions	PROTOCOL DURATION Run‐in = 2 to 3 weeks Intervention = 12 weeks DEVICE: medication or placebo given by the Pari LC‐Jet Plus nebuliser connected to a Pari Master compressor (Pari Respiratory Equipment, Inc, Richmond, VA) with use of a mouthpiece or face mask DOSE OF ICS INTERVENTION: budesonide 250 μg/d CONTROL: budesonide 500 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: reported
Outcomes	ANALYSIS: Done in "all patients treated" (intention‐to‐treat). Analysis of variance techniques and Fisher's exact test used OUTCOMES: GROWTH MEASUREMENT TECHNIQUE: not reported PULMONARY FUNCTION TESTS Mean change in FEV1 throughout weeks 0 to 12 Mean change in morning and evening PEFR throughout weeks 0 to 12 FUNCTIONAL STATUS Change from baseline in daytime and nighttime symptoms BIOMARKERS Serum cortisol after ACTH stimulation test ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (1999) FUNDING: supported in part by Astra USA CONFIRMATION OF METHODOLOGY: not received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation
Allocation concealment (selection bias)	Unclear risk	Insufficient information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of participants and key study personnel ensured
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	Study protocol not available but published reports include all expected outcomes, including those that were prespecified
Other bias	Low risk	Study apparently free of other sources of bias