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.

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.