Kemp 1999.

Methods	DESIGN: multi‐centre, randomised, double‐blind, placebo‐controlled, parallel‐group study
Participants	SYMPTOMATIC PARTICIPANTS RANDOMLY ASSIGNED: N = 174 INTERVENTION: ICS (budesonide 250 μg/d): 91 CONTROL: ICS (budesonide 500 μg/d): 83 WITHDRAWALS: reported AGE: mean (range) (months) INTERVENTION: ICS (budesonide 250 μg/d): 55.2 ± 25.5 (7‐107) CONTROL: ICS (budesonide 500 μg/d): 52.4 ± 27.9 (10‐107) GENDER: male N (%) INTERVENTION: ICS (budesonide 250 μg/d): 63 (69.2) CONTROL: ICS (budesonide 500 μg/d): 58 (69.9) ASTHMA SEVERITY: mild persistent asthma ASTHMA DURATION: mean (range) in months INTERVENTION: ICS (budesonide 250 μg/d): 35.4 ± 22.4 (5‐97) CONTROL: ICS (budesonide 500 μg/d): 36.7 ± 25.1 (5‐107) MEAN (± SD) β2‐AGONIST USE (puffs/d): not reported DOSE OF ICS AT STUDY ENTRY AND AT RUN‐IN: not reported. Participants discontinued their chronic asthma medication at the end of the study ATOPY (% of participants): not reported ELIGIBILITY CRITERIA Age of 6 months to 8 years Clinically diagnosed with asthma Exacerbations of cough or wheezing in the 6 months before the study Daily use of at least 1 chronic asthma medication Periodic use of a bronchodilator for at least 3 months before enrolment FEV1 ≥ 50% of predicted normal and reversibility of 15% after albuterol (if possible to perform spirometric) EXCLUSION CRITERIA Severe or unstable asthma Symptoms limited to seasonal allergen exposure Oral GCSs used intermittently within 30 days or prolonged treatment within 12 weeks of enrolment Hospitalised for treatment of air obstruction within 30 days of enrolment Upper or lower respiratory tract infection within 14 days of enrolment Any other concomitant lung disease
Interventions	PROTOCOL DURATION Run‐in = 2 weeks Intervention = 12 weeks DEVICE: Pari LC‐Jet Plus nebuliser (with mouthpiece or face mask) DOSE OF ICS INTERVENTION: budesonide 250 μg/d CONTROL: budesonide 500 μg/d CRITERIA FOR WITHDRAWAL FROM STUDY: not reported
Outcomes	ANALYSIS: intention‐to‐treat analysis; ANOVA; Fisher's exact test OUTCOMES: at enrolment, at randomisation, after 2, 4, 8 and 12 weeks of treatment GROWTH MEASUREMENT TECHNIQUE: not reported PULMONARY FUNCTION TESTS Change in FEV1 percentage predicted between baseline and week 12 Absolute change in FEV1 Change in AM PEFR and PM PEFR from baseline FUNCTIONAL STATUS Nighttime and daytime asthma symptom scores Change from baseline in number of days that breakthrough medication was used BIOMARKERS: baseline and at end of study (12 weeks) Blood samples for cortisol measurements and cosyntropin stimulation test ADVERSE EVENTS: reported WITHDRAWALS: reported
Notes	PUBLICATION: full paper (1996) FUNDING: funded by AstraZeneca 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