title: Tiotropium in asthma: a systematic review.
abstract: BACKGROUND
  The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use.
  
  
  METHODS
  With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were "tiotropium and asthma." The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided.
  
  
  RESULTS
  Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial.
  
  
  CONCLUSIONS
  The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled β2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS-LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy.
  
  
  CONCLUSIONS
  Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns.
authors.affiliation: MedStar Washington Hospital Center, Washington, DC, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Befekadu
authors.affiliation: MedStar Washington Hospital Center, Washington, DC, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Onofrei
authors.affiliation: MedStar Washington Hospital Center, Washington, DC, USA ; The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Gene L
authors.initials: GL
authors.lastname: Colice
keywords: LABA; LAMA; asthma; inflammation; inhaled corticosteroid; lung; tiotropium