Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year.
OBJECTIVE
Increasing evidence suggests that low-dose theophylline has anti-inflammatory benefits and is safe in the treatment of COPD. This study aims to evaluate the efficacy and safety of low-dose, slow-release oral theophylline administered over a 1-year period in patients with COPD.


METHODS
A randomized, double-blind, parallel-group, placebo-controlled trial was carried out. In total, 110 participants with COPD were randomly assigned to receive slow-release theophylline (100 mg b.i.d.) or placebo for 1 year. Use of medicine and symptoms recorded by diary cards; pulmonary function, exacerbations of COPD, quality of life and the use of rescue medicine were evaluated. Superiority test was used to estimate the efficacy.


RESULTS
Of 110 participants, 85 (77.3%) complied with the protocol, with 42 subjects in theophylline and 43 subjects on placebo. In both intention-to-treat and per-protocol population analysis, greater improvement in pre-bronchodilator FEV(1) (P = 0.038 and P = 0.070, respectively), lower frequency of COPD exacerbations (P = 0.047 and P = 0.035, respectively), fewer days of COPD exacerbations (P = 0.045 and P = 0.046, respectively), lower frequency of clinical visits (P = 0.017 and P = 0.039, respectively), greater improvement in satisfaction with treatment (P = 0.014 and P = 0.004, respectively) were found in the theophylline group than in the placebo group. In per-protocol population, greater improvements in quality of life (P = 0.047) were also observed in the theophylline group and the mean time to the first exacerbation was delayed in theophylline group in comparison with placebo group (P = 0.047). Drug-related adverse events such as stomach discomfort (3.51%), headache (3.51%), insomnia (1.75%) and palpitation (1.75%) were found in the theophylline group.


CONCLUSIONS
Low-dose, slow-release oral theophylline is effective and well-tolerated in the long term treatment of stable COPD, although it does not improve post-bronchodilator lung function.
Zhou
Yumin
Y
Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital Of Guangzhou Medical College, 151 Yanjiangxi Road, Guangzhou 510120, China.
Wang
Xiaoping
X
Zeng
Xiangyi
X
Qiu
Rong
R
Xie
Junfeng
J
Liu
Shengming
S
Zheng
Jingping
J
Zhong
Nanshan
N
Ran
Pixin
P
D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D011788:Quality of Life; D013806:Theophylline / Q000008:administration & dosage* / Q000009:adverse effects
D001993:Bronchodilator Agents; D013806:Theophylline