Mulloy 1993.

Methods	1) Randomisation: not specified. 2) Allocation concealment: The treatment packs containing medications were sealed in advance. 3) Masking: Double blind, placebo controlled. 4) Withdraw/Drop‐out: 2/12 (17%). 5) Duration of intervention: 3 weeks x 2 (first week dose adjustments followed by 2 weeks of treatment). 6) Design: Crossover group. 7) Jadad quality score: 3 8) Location: Dublin, Ireland
Participants	1) Inclusion criteria:COPD, clinically stable. 2) Definition of COPD: FEV1 less than 50% of predicted, with less than 15% improvement in FEV1 2O min. after 400 ug of salbutamol via inhaler. 3)Type of exercise test: Incremental treadmill exercise testing 4) Definition of stable COPD: Yes, (none had exacerbation of the COPD for at least 6 wk before entry into the study. 5) Age: (range 51 to 84). Mean = 4.2, SD 5.39 6) FEV1: 0.74 to 1.39 (range 20 to 47%). Mean = 0.91, SD 0.21 7) Number of patients: 12 ( 9 men and 1 woman). 2 drop‐out. Final number of patients: 10. 8) Baseline therapy: Predinisone, duovent inhaler, beclomethasone inhaler, ipratropium inhaler, salbutamol inhaler, theophylline. 9) Exclusion criteria: history of cardiac (other than cor pulmonale) or hepatic disease. Taking hypnotics, sedatives, or any medication known to interfere with the metabolism or absorption of theophylline, smokers, asthma, blood eosinophilia.
Interventions	THEOPHYLLINE GROUP (n=10, completed the study) 1) Drug: Theophylline (Napp Lab, Cambridge) 2) Short or long action: Long‐action 3) Dose: 400 mg theophylline bd (10:00 AM and 10 PM). Patients weighing less than 70 kg took 300 mg bd. 4) Washout: 1 week, when dose adjustments were made for both the active and placebo arms. 5) Theophylline blood level: measured during the first week in baseline period and during the subsequent week in both active and placebo groups. The dose was adjusted in a blinded fashion in those on active treatment. Adjustments were made until all patients had a blood level between 10 and 20 mg/l. PLACEBO GROUP (n = 10, completed the study).
Outcomes	1) Pulmonary function tests 2) Incremental exercise testing 3) Resting arterial blood gases and oxygen saturation. 4) Sleep alterations 5) Side effects: Nausea, only one patient (this patient had not taken theophylline before as the other 9 had).
Notes	1) Intention‐to‐treat analyses: No. 2) Sample size and statistical power: not reported. 3) Representativity: Yes. Randomised outpatients.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate