title: Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial.
abstract: BACKGROUND
  Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients.
  
  
  OBJECTIVE
  We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 μg daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, ≥ 1.5; postbronchodilator FEV₁, ≤ 80% of predicted value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting β₂-agonist.
  
  
  METHODS
  This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV₁ at the end of each treatment period.
  
  
  RESULTS
  Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV₁, 65% of predicted value), 100 completed all periods. Peak FEV₁ was significantly higher with 5 μg (difference, 139 mL; 95% CI, 96-181 mL) and 10 μg (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001). There was no significant difference between the active doses. Trough FEV₁ at the end of the dosing interval was higher with tiotropium (5 μg: 86 mL [95% CI, 41-132 mL]; 10 μg: 113 mL [95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 μg of tiotropium.
  
  
  CONCLUSIONS
  The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting β₂-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma.
authors.affiliation: Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.a.m.kerstjens@long.umcg.nl
authors.forename: Huib A M
authors.initials: HA
authors.lastname: Kerstjens
authors.forename: Bernd
authors.initials: B
authors.lastname: Disse
authors.forename: Winfried
authors.initials: W
authors.lastname: Schröder-Babo
authors.forename: Theo A
authors.initials: TA
authors.lastname: Bantje
authors.forename: Martina
authors.initials: M
authors.lastname: Gahlemann
authors.forename: Ralf
authors.initials: R
authors.lastname: Sigmund
authors.forename: Michael
authors.initials: M
authors.lastname: Engel
authors.forename: Jan A
authors.initials: JA
authors.lastname: van Noord
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide