Nagel 1988.

Study characteristics
Methods	Country: United Kingdom Design: randomised, double‐blind, cross‐over study Objective/aim: to find out if there was a difference in the degree of GORD between people with asthma with "morning dipping", in which the PEFR falls during the night, and people with asthma in which this does not occur ("non‐dippers"); also, to see if people with asthma with GORD given ranitidine or placebo would benefit from reduction of acidity in the stomach Study site: outpatient Methods of analysis: 2‐sample Wilcoxon test; Chi²; and 2‐samples t‐tests or t‐tests for paired differences
Participants	Eligible for study: 15 Randomisation: 15 Participants completed: 14 Age, mean (range): 42 (20 to 64) Gender, M/F: 11/4 Co‐morbidities: not mentioned Diagnostic criteria for asthma: doctor's diagnosis and objective lung function Diagnostic criteria for GORD: symptoms, 24‐hour pH monitoring: required pH < 4 for > 4.2% of the time or > 3 episodes of reflux lasting longer than 5 minutes; required to have symptomatic GORD at least once every 6 weeks Association between asthma and GORD tested? Yes; association required for entry, tested by history, symptoms, and 24‐hour pH monitoring associated with a dip in PEFR during the night Major exclusion criteria: not specified Baseline severity of asthma: FEV₁ > 25% reversibility after bronchodilators; PEFR > 25% reversibility after bronchodilators Baseline severity of GORD: symptoms occurred at least once every 6 weeks Baseline complications of GORD: not specified
Interventions	Duration of intervention: 7 days plus 3‐day washout period Type of intervention: ranitidine 300 mg at 9 pm and 150 mg at 9 am Type of control: placebo
Outcomes	Pre‐specified outcomes: not specified Follow‐up period: 17 days Outcomes measured: mPEFR, ePEFR, use of beta₂‐agonists, asthma symptoms, reflux symptoms (number of people)
Notes	*Indicates significant result
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation reported but method not described
Allocation concealment (selection bias)	Unclear risk	No details specified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind reported but no details specified
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind reported but no details specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawals reported with explanation
Selective reporting (reporting bias)	Unclear risk	Pre‐specified outcomes not specified
Other bias	Low risk	No other significant bias detected