Mahler 1985.

Methods	1) Randomisation: not described. 2) Allocation concealment: not described. 3) Masking: Double blind, with placebo identical in appearance to theophylline tablets. 4) Withdraw/Drop‐out: none. 5) Duration of intervention: 2 x 4 weeks 6) Design: Cross‐over groups 7) Jadad quality score: 3 8) Location: West Haven, Connecticut, USA
Participants	1) Inclusion criteria:COPD, stable, outpatients, at least moderate air‐flow obstruction, less than 65 % of predicted, ability to exercise on an upright bicycle ergometer, and willingness to discontinue all medications for the period of the study. 2) Definition of COPD: FEV1 at least less than 65% of predict, with nonreversible airway obstruction, defined as less than 15% improvement in FEV1 after an inhaled bronchodilator. 3)Type of exercise test: 12 min walking test and submaximal steady state as well as progressive, incremental exercise on the bicycle ergometer. 4) Definition of stable COPD: not described. 5) Age: Mean = 60, SD 7 years 6) FEV1: Mean = 40 (% pred) and Mean= 1.36, SD 0.67 (L) 7) Number of patients: 12 men. withdraw: 0 8) Baseline therapy: Patients were instructed to use only an inhaled bronchodilator for respiratory symptoms. 9) Exclusion criteria: History of asthma or electrocardiographic evidence of coronary artery disease, valvular heart disease, hypertension, or primary myocardial disease.
Interventions	THEOPHYLLINE GROUP (n = 12, completed the study) 1) Drug: Theophylline (Theo‐Dur, Key Pharmaceutical, Inc., Miami, FL) 2) Short or long action: Long‐action 3) Dose: Initial 13 mg/Kg/day in 2 divided doses based on lean body weight. 4) Washout: 2 weeks 5) Theophylline blood level: measured on the fourth day of the study, theophylline blood level measured using HPLC in patients receiving theophylline as well as placebo. If the level was less than 10 um/ml, then the dosage was increased by 200 to 400 mg/day; in those receiving placebo, the dosage was randomly changed on the fourth day in some patients. In all patients who had a change in initial dosage of medication, theophylline level was remeasured on the seventh day. All patients receiving theophylline had a therapeutic blood level (10 to 20 ug/ml). PLACEBO GROUP ( n = 12, completed the study ).
Outcomes	1) Pulmonary function tests (FVC (L), TLC (by body plethysmography), DLCO (ml/min/mmHg), FEV1 (L), FEV1 (% Pred). 2) Exercise testing: 12 min walking test (incremental and endurance exercise cycle ergometer test ‐ WR, VO2max, HR, respiratory rate and ventilation, VO2max/HR, VEmax/MVV, anaerobic threshold (VE/VO2slope). 3) Resting arterial blood gases 4) Dyspnea index 5) Side effects: none occured. All patients tolerated the theophylline and placebo medications without adverse effects.
Notes	1) Intention‐to‐treat analyses: Yes 2) Sample size and statistical power: not reported. 3) Representativity: yes. 20 patients with COPD were selected from outpatient clinics. After specific tests 12 patients were selected for the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear