title: Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.
abstract: BACKGROUND
  Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated.
  
  
  METHODS
  Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio.
  
  
  RESULTS
  We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003).
  
  
  CONCLUSIONS
  This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón; Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japón. Electronic address: nobuyuki_horita@yahoo.co.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Horita
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón; Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japón.
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyazawa
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón; Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japón.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kojima
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón; Department of Respiratory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japón.
authors.forename: Miyo
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japón; Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japón.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000368:Aged; D001993:Bronchodilator Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D064887:Observational Studies as Topic; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D013806:Theophylline / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D013806:Theophylline
keywords: Adverse effect; Bronchodilator; Broncodilatador; Death; Drug toxicity; Efectos adversos; Emphysema; Enfisema; Muerte; Toxicidad de los fármacos