Chrystyn 1988.

Methods	1) Randomisation: patients were randomly allocated to the order of treatment by four identical Latin squares. 2) Allocation concealment: Not described. 3) Masking: The dose changes were effected in a single blind manner with matching placebo tablets. 4) Withdraw/Drop‐out: 5 drop‐out /38 (13,16%). 5) Duration of intervention: 2 months. 4 consecutive two month treatment periods (total = 8 months). Four periods: placebo, low, medium and high theophylline serum concentrations. 6) Design: Crossover groups. 7) Jadad uality score: 2 8) Location: West Yorkshire, UK
Participants	1) Inclusion criteria:COPD, moderate to severe obstruction of airflow. 2) Definition of COPD: Medical Research Council definition. 3)Type of exercise test: Six min waking test 4) Definition of stable COPD: not defined. But no patients were recruited who had an acute exacerbation in the previous 2 weeks. 5) Age: Mean = 61.2, SD 5.71 years (range 53 to 73) 6) FEV1: Mean = 29.1, SD 12.4 (% predc) 7) Initial total number of patients: 38. Drop‐out: 5. Final patients number: 33 ( 30 men and 3 women). 8) Baseline therapy: Inhalation and oral corticosteroids and other bronchodilators were continued. 9) Exclusion criteria:Asthma or allergy, > = 15% improvement in FEV1 20 min after inhaling 500 ug terbutaline sulphate, known sensitivity to methylxanthine, severe cardiac disease or other disease that might interfere with exercise testing.
Interventions	THEOPHYLLINE 3 GROUP‐ low dose ( n = 19), medium dose (n = 12), high dose (n = 10), completed the study. 1) Drug: Theophylline 2) Short or long action: Long‐action 3) Dose: 3 doses used; low (5 to 10 mg/l), medium (10 to 15 mg/l) and high (15 to 20 mg/l). Used the medium dose only for the review as it is clinically the most relevant dose resulting in therapeutic plasma levels. 4) Washout period: not mentioned. 5) Theophylline blood level: measured at the end of each two month period. PLACEBO GROUP ( n = 22 )
Outcomes	1) Pulmonary function tests (FEV1), (FVC), (SVC) (L), TLC measured by helium dilution (L), FRC measured by helium dilution (L), TLC measured by whole body plesthymography (L), FRC measured by whole body plesthymography (L) and trapped gas volume (L). 2) Exercise testing : six minute walking test 3) Visual analogue scale for dyspnoea (10 cm) 4) Peak expiratory flow (L/min.) 5) Side effects: nausea, insomnia, dyspepsia, headache, cramp, tremor (theophylline group)
Notes	1) Intention‐to‐treat analyses: Yes 2) Sample size and statistical power: not reported. 3) Representativity: not specified
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear