title: Tiotropium versus placebo for inadequately controlled asthma: a meta-analysis.
abstract: OBJECTIVE
  This meta-analysis was performed to evaluate the efficacy and safety of the addition of tiotropium to standard treatment regimens for inadequately controlled asthma.
  
  
  METHODS
  A systematic search was made of PubMed, EMBASE, MEDLINE, and CENTRAL databases, and ClinicalTrials.gov, and a hand search of leading respiratory journals. Randomized, double-blind clinical trials on the treatment of inadequately controlled asthma for ≥ 4 weeks with the addition of tiotropium, compared with placebo, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMDs), with 95% CI.
  
  
  RESULTS
  Six trials met the inclusion criteria. The addition of tiotropium, compared with placebo, significantly improved all spirometric indices, including morning and evening peak expiratory flow (WMD 20.59 L/min, 95% CI 15.36-25.81 L/min, P < .001; and WMD 24.95 L/min, 95% CI 19.22-30.69 L/min, P < .001, respectively), trough and peak FEV1 (WMD 0.13 L, 95% CI 0.09-0.18 L, P < .001; and WMD 0.10 L, 95% CI 0.06-0.14 L, P < .001, respectively), the area under the curve of the first 3 h of FEV1 (WMD 0.13 L, 95% CI 0.08-0.18 L, P < .001), trough and peak FVC (WMD 0.1 L, 95% CI 0.05-0.15 L, P < .001; and WMD 0.08 L, 95% CI 0.04-0.13 L, P < .001, respectively), the area under the curve of the first 3 h of FVC (WMD 0.11 L, 95% CI 0.06-0.15 L, P < .001). The mean change in the 7-point Asthma Control Questionnaire score (WMD -0.12, 95% CI -0.21 to -0.03, P = .01) was markedly lower in tiotropium group, but not clinically important. There were no significant differences in Asthma Quality of Life Questionnaire score (WMD 0.09, 95% CI -0.01 to 0.20, P = .09), night awakenings (WMD 0.00, 95% CI -0.05 to 0.05, P = .99) or rescue medication use (WMD -0.18, 95% CI -0.36 to 0.00, P = .06). No significant increase was noticed in adverse events in the tiotropium group (OR 0.80, 95% CI 0.62-1.03, P = .08).
  
  
  CONCLUSIONS
  The addition of tiotropium to standard treatment regimens has significantly improved lung function without increasing adverse events in patients with inadequately controlled asthma. Long-term trials are required to assess the effects of the addition of tiotropium on asthma exacerbations and mortality.
authors.affiliation: Department of Respiratory Diseases.
authors.forename: Jing-wei
authors.initials: JW
authors.lastname: Tian
authors.forename: Jin-wu
authors.initials: JW
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D010919:Placebos / Q000627:therapeutic use; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013147:Spirometry; D000069447:Tiotropium Bromide; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D010919:Placebos; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: anticholinergics; asthma; inadequately controlled asthma; meta-analysis; tiotropium