Asthma and lower airway disease
Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial

Accepted for presentation at the 2010 Annual Meeting of the European Respiratory Society, Barcelona, Spain.
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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.

Section snippets

Trial design

This randomized, double-blind, placebo-controlled, crossover study with three 8–week treatment periods was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent for participation in the clinical trial. The trial was registered at www.clinicaltrials.gov (NCT00365560). After a 2-week run-in period, eligible patients were randomized and entered a 24–week, double-blind treatment period. Visits occurred at the start of the trial (screening), at

Results

Patients were enrolled between August 2006 and November 2007. Of 132 patients screened, 110 were eligible for the trial, 107 were randomized, and 100 completed all 3 treatment periods (Fig 1). The demographic characteristics of randomized patients at screening are summarized in Table I. Medication used before the screening visit comprised LABAs and ICSs (per inclusion criteria), rapidly acting β-agonists (77%), short-acting anticholinergics (21%; no long-acting anticholinergics were used),

Discussion

Tiotropium resulted in significant bronchodilatation in patients with severe asthma not adequately controlled by maximal treatment according to guidelines, including a combination of high-dose ICS plus LABA treatment. The bronchodilator effect was not different between the 2 doses and was not associated with significant improvement in any related outcome.

Although most patients with asthma can achieve control with appropriate medication according to the guidelines, some patients remain

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  • Cited by (0)

    Supported by Boehringer Ingelheim and Pfizer.

    Disclosure of potential conflict of interest: H. A. M. Kerstjens receives research support from Boehringer Ingelheim and Pfizer and has consulted with Boehringer Ingelheim. J. A. van Noord receives research support from Boehringer Ingelheim, Chiesi, Novartis, and GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest.

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