Tiotropium Improves Lung Function in Patients With Severe Uncontrolled Asthma: A Randomized Controlled Trial

J Allergy Clin Immunol. 2011 Aug;128(2):308-14. doi: 10.1016/j.jaci.2011.04.039. Epub 2011 Jun 2.

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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00365560.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects*
  • Bronchodilator Agents / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Quality of Life
  • Respiratory Function Tests
  • Scopolamine Derivatives / administration & dosage
  • Scopolamine Derivatives / adverse effects*
  • Scopolamine Derivatives / therapeutic use*
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Tiotropium Bromide
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Scopolamine Derivatives
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT00365560