Oral theophylline compared to placebo for people with chronic obstructive pulmonary disease (COPD)

Theophylline treatment is commonly used in people with chronic obstructive pulmonary disease (COPD). This systematic review shows that orally administered theophylline improves lung function and levels of oxygen and carbon dioxide in the blood. However, there is limited data on its effect on symptoms, exercise capacity or quality of life. Despite being associated with increased side effects, particularly nausea, participants preferred theophylline over placebo.

Authors' conclusions: 

Theophylline has a modest effect on FEV1 and FVC and slightly improves arterial blood gas tensions in moderate to severe COPD. These benefits were seen in participants receiving a variety of different concomitant therapies. Improvement in exercise performance depended on the method of testing. There was a very low dropout rate in the studies that could be included in this review, which suggests that recruited participants may have been known by the investigators to be theophylline tolerant . This may limit the generalisability of these studies.

Read the full abstract...

Oral theophylline has, for many years, been used as a bronchodilator in patients with COPD. Despite the introduction of new drugs, and its narrow therapeutic index, theophylline is still recommended for COPD treatment.


To determine the effectiveness of oral theophylline when compared to placebo in patients with stable COPD.

Search strategy: 

We searched the Cochrane Airways Group trial register and Cochrane Central Register of Controlled Trials Cochrane Controlled Clinical Registers were searched.

Selection criteria: 

All studies were randomised controlled trials (RCTs).

Data collection and analysis: 

Two reviewers independently abstracted data and asessed the methodological quality.

Main results: 

Twenty RCTs met the inclusion criteria. Concomitant therapy varied from none to any other bronchodilator plus corticosteroid (oral and inhaled). The following outcomes were significantly different when compared to placebo.

Forced expiratory volume in one second (FEV1) improved with treatment: Weighted Mean Difference (WMD) 100 ml; 95% Confidence Interval (CI) 40 to 160 ml. Similarly for forced vital capacity (FVC): WMD 210 ml 95%CI 100 to 320. Two studies reported an improvement in maximum oxygen consumption (VO2 max); WMD 195 ml/min, 95%CI 113 to 278. At rest, arterial oxygen tension at rest (PaO2) and arterial carbon dioxide tension at rest (PaCO2) both improved with treatment (WMD 3.2 mm Hg; 95%CI 1.2 to 5.1, and WMD -2.4 mm Hg; 95%CI -3.5 to -1.2, respectively). Walking distance tests did not improve (four studies, Standardised Mean Difference 0.30, 95%CI -0.01 to 0.62), neither did Visual Analogue Score for breathlessness in two small studies (WMD 3.6, 95%CI -4.6 to 11.8). The Relative Risk (RR) of nausea was greater with theophylline (RR 7.7; 95%CI 1.5 to 39.9). However, patients' preference for theophylline was greater than that for placebo (RR 2.27; 95%CI 1.26 to 4.11). Very few participants withdrew from these studies for any reason.