title: Tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe chronic obstructive pulmonary disease: A meta-analysis.
abstract: OBJECTIVE
  This meta-analysis was performed to compare the risks and benefits of combined treatment with tiotropium plus formoterol versus tiotropium alone for stable moderate-to-severe COPD.
  
  
  METHODS
  A comprehensive search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) that compared formoterol plus tiotropium to tiotropium alone in COPD patients with a duration of at least 4 weeks. The cut-off date for the search was July 1, 2015. The odds ratio (OR) or mean difference (MD) was used to pool the results with 95% confidence intervals (CI).
  
  
  RESULTS
  Eight randomized controlled trials were eligible for this meta-analysis. A significant improvement was observed among patients treated with tiotropium plus formoterol compared with tiotropium alone in the following spirometric indices: mean change in trough FEV1 (P = .02), trough FVC (P = .007), peak FEV1 (P < .00001), and peak FVC (P < .00001). A similar result was noted for the transitional dyspnea index (TDI) (MD 1.46; 95% CI 1.07-1.85) and a clinically significant change in TDI between the tiotropium plus formoterol and tiotropium alone groups (P < .00001). Moreover, a trend toward fewer adverse events was seen in the combination treatment group compared with the tiotropium group (OR .88; 95% CI .70-1.11), although this difference was not statistically significant.
  
  
  CONCLUSIONS
  Compared with tiotropium alone, tiotropium in combination with formoterol improved lung function and the symptoms of dyspnea in stable moderate-to-severe COPD patients. Moreover, the combined treatment group tended to have fewer adverse events compared with the tiotropium treatment alone group.
authors.affiliation: Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, 136 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, 136 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, 136 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Lu
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Zi An
authors.initials: ZA
authors.lastname: Xia
authors.affiliation: Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, 136 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.affiliation: Thyroid Tumour Internal Medicine Department, Cancer Hospital affiliated to Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gerontology and Respiratory Diseases, Xiangya Hospital, Central South University, 136 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D000069447:Tiotropium Bromide / Q000008:administration & dosage*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
keywords: chronic obstructive pulmonary disease; formoterol; meta-analysis; tiotropium