[Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease].
OBJECTIVE
To evaluate the efficacy and safety of oral theophylline versus placebo in patients with stable chronic obstructive pulmonary disease (COPD).


METHODS
The databases Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese Biomedical Database were retrieved by using the key words "Uniphyl or Theophylline or Theo-Dur or theo or Theotrim or Elixophyllin or Elixophyllin or Phyllocontin or aminophylline or Methylxanthine or nuelin or doxofylline" and "obstructive or bronchitis or pulmonary emphysema or bronchial hyperreactivity or COPD or COLD or emphysema" so as to search the materials about the randomized controlled clinical trials comparing the effectiveness of stable COPD treated by oral theophylline and placebo. A meta-analysis was conducted. For continuous variables, the results of individual studies were pooled using fixed-effect weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). Where the results were expressed as dichotomous variables, the relative risk (RR) with 95%CI was calculated.


RESULTS
Thirty-four documents about randomized controlled clinical trials, including a total of 2087 patients, from the retrieved 2010 documents accorded to the demand of enrollment. The results of meta-analysis showed that theophylline significantly improved the forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate (WMD 0.09 L, 95%CI 0.09 - 0.09; WMD 0.14 L, 95%CI 0.13 - 0.14; WMD 17.0 L/min and 95%CI 6.9 - 27.2 respectively). Arterial oxygen tension and arterial carbon dioxide tension at rest both improved with treatment (WMD 2.89 mm Hg, 95%CI 1.11 - 4.66; WMD -2.05 mm Hg and 95%CI -3.59 to -1.42 respectively). Six-minute walk distance significantly improved (WMD 38.89 meters, 95%CI 21.55 - 56.22) in treatment group. The RR of acute exacerbations was smaller between both groups (RR 0.74, 95%CI 0.59 - 0.93). The RR of total adverse events was similar (RR 1.05, 95%CI 0.95 - 1.16) while RR of drug-related adverse events was greater (RR 2.54, 95%CI 1.37 - 4.70). And there was significant statistical difference.


CONCLUSIONS
Compared with the placebo, theophylline can improve lung function, arterial blood gas tensions and walking distance while the incidence of drug-related adverse events is higher.
Wang
Chang-Hui
CH
Department of Respiratory Medicine, Tenth People's Hospital of Tongji University, Shanghai 200072, China.
Zhang
Qian
Q
Li
Ming
M
Fu
Pei-Fang
PF
Yan
Zheng-Mao
ZM
Peng
Ai-Mei
AM
Zhang
Guo-Liang
GL
D000284:Administration, Oral; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
D013806:Theophylline