Methods	Cross-over, single centre study in UK
Participants	% ELIGIBLE OF SCREENED POPULATION: Not specified % RUN-IN PARTICIPANTS RANDOMISED: 74 RANDOMISED: 49 WITHDRAWALS: 10 GENDER: (% male): 51 MEAN AGE: 42 SEVERITY: Not stated BASELINE FEV1 % PREDICTED: 74.8 BASELINE DOSE OF ICS: </−400 BDP ASTHMA DURATION: Not available ATOPIC: 93% SMOKING STATUS: Non or ex-smokers eligible INCLUSION CRITERIA: 18 to 75 years, diagnosed with asthma; receiving treatment with 400 mcg/day beclomethasone dipropionate; one or more of 1) > 15% increase in FEV1 post-SABA; 2) > 20% within-day variability in PEF assessed twice daily over a 2-week period; 3) provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) < 8mg/mL-1; following run-in on 200 mcg day BUD, participants were eligible if they had recorded day or nighttime asthma symptoms on their diary cards on at least 4 days in the third or fourth baseline week EXCLUSION: Current smokers or smoking history of > 10 pack-years, significant comorbidity, treated with oral corticosteroids, long-acting b2-agonists, leukotriene antagonists or theophylline; asthma exacerbation or lower respiratory tract infection within the 4 weeks prior to trial entry
Interventions	LABA + ICS vs INCREASED dose of ICS OUTCOMES: 4 weeks RUN-IN PERIOD: 4 weeks DOSE OF ICS DURING RUN-IN: BUD 100 mcg bid TREATMENT DURATION: 4 weeks DOSE OPTIMISATION PERIOD: None TEST GROUP: Budesonide 100 mg bid + formoterol 12 mg bid CONTROL GROUP: Budesonide 400 mg bid DEVICE: Turbohaler NUMBER OF DEVICES: 2 (double-dummy) COMPLIANCE: Not assessed CO-TREATMENT: prn SABA
Outcomes	PULMONARY FUNCTION TESTS: am PEF; FEV1 SYMPTOM SCORES: *VAS; daytime symptoms; nocturnal symptoms FUNCTIONAL STATUS Quality of life (AQLQ); exacerbations (deterioration in PEF or requirement for OCS. Patients who experienced 2 or more exacerbations were withdrawn from the study) INFLAMMATORY MARKERS: *Sputum eosinophils; exhaled nitric oxide; *PC20 ADVERSE EFFECTS: Not reported WITHDRAWALS: Stated (not by treatment group) Primary outcome measure*
Notes	Full-text article Funding source: Not disclosed Methodology and data: TJL emailed 17 April 2008. Response from RG with details of randomisation and data User defined: 800
Risk of bias
Item	Authors’ judgement	Description
Adequate sequence generation?	Yes	“I believe that this was generated using a computer statistical package generating a random sequence. I don’t know the package that was used and unfortunately the individual has left our organisation but had extensive clinical trials expertise.”
Allocation concealment?	Yes	“…this was indeed generated by a third party, namely the pharmacist responsible for dispensing the double blind medication (…) None of the study investigators were aware of the randomisation schedule until the last patient had completed the cross-over study”
Blinding? All outcomes	Yes	Double-dummy
Incomplete outcome data addressed? All outcomes	No	Completers used for analysis
Free of selective reporting?	Yes	OCS-treated exacerbations reported. Data could not be extracted as only data on events and not number of participants were made available