Chest
Volume 128, Issue 3, September 2005, Pages 1168-1178
Journal home page for Chest

Clinical Investigations
Improvements in Symptom-Limited Exercise Performance Over 8 h With Once-Daily Tiotropium in Patients With COPD

https://doi.org/10.1378/chest.128.3.1168Get rights and content

Study objectives

We have previously shown that tiotropium at 18 μg reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. The present study was designed to gain further insight into the duration of improvements.

Design, patients, and interventions

A randomized, double-blind, placebo-controlled, parallel-group study was conducted in 261 COPD patients (mean age, 62.5 ± 7.4 years [± SD]; 189 men and 72 women; mean FEV1, 1.2 ± 0.4 L [43 ± 12.7% predicted]). On day 0 (first dose), day 21, and day 42 of treatment, pulmonary function tests were performed before and 1 h 20 min after dosing, followed by a constant work rate cycle ergometry test (75% maximum work capacity) to symptom limitation at 2.25 h after dosing. On day 42, an additional constant work rate cycle ergometry test was performed at 8 h after dosing.

Results

Adjusted mean (± SE) endurance time (ET) on day 42 was 803 ± 40 s (tiotropium), vs 568 ± 42 s (placebo) at 2.25 h after dosing (primary end point; treatment difference, 236 ± 58 s; p = 0.0001) and 665 ± 40 s (tiotropium) vs 494 ± 42 s (placebo) at 8 h after dosing (treatment difference, 171 ± 58 s; p = 0.0035). Adjusted mean dyspnea intensity at isotime on day 42 was 4.60 ± 0.16 Borg units (tiotropium), vs 5.65 ± 0.16 Borg units (placebo) at 2.25 h after dosing (p < 0.001), and 5.54 ± 0.17 Borg units (tiotropium) vs 6.51 ± 0.18 Borg units (placebo) at 8 h after dosing (p < 0.001). Adjusted mean pre-exercise inspiratory capacity (IC) on day 42 was 2.41 ± 0.03 L (tiotropium) vs 2.19 ± 0.03 L (placebo) at 2.25 h after dosing (p < 0.001), and 2.31 ± 0.03 L (tiotropium) vs 2.16 ± 0.03 L (placebo) at 8 h after dosing (p < 0.001). The significant increase in IC with tiotropium compared with placebo was maintained throughout exercise.

Conclusions

The present study confirms that tiotropium reduces lung hyperinflation at rest and during exercise, reduces exertional dyspnea, and improves symptom-limited exercise tolerance in COPD patients. Furthermore, this study shows that this improvement is present at 2.25 h and at 8 h after dosing after 6 weeks of treatment.

Section snippets

Study Subjects

Patients with a clinical diagnosis of COPD based on American Thoracic Society criteria15 were eligible for the trial (Boehringer Ingelheim 205.223) if they fulfilled the following criteria: age 40 to 75 years, cigarette smoking > 10 pack-years, FEV1 ≤ 65% predicted, and functional residual capacity (FRC) measured by body plethysmography ≥ 120% predicted. Patients with a history of asthma, allergic rhinitis, or atopy were not eligible for the trial. Also, patients with any recognized

References (28)

  • O’DonnellDE et al.

    Exertional breathlessness in patients with chronic airflow limitation: the role of hyperinflation

    Am Rev Respir Dis

    (1993)
  • O’DonnellDE et al.

    Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (1998)
  • DiazO et al.

    Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest

    Eur Respir J

    (2000)
  • O‘DonnellDE et al.

    Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2001)
  • Cited by (299)

    • Pathogenesis and management of emphysema in people with HIV

      2023, Expert Review of Respiratory Medicine
    View all citing articles on Scopus

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    A list of participants is given in the Appendix.

    This study was supported by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany, and Pfizer, Inc., New York, NY.

    Drs. Maltais, Marciniuk, Hernandez, Sciurba, and O'Donnell have received fees from Boehringer Ingelheim for participating in clinical research, advisory board meetings, and continuing medical education events. Drs. Kesten and Hamilton are employees of Boehringer Ingelheim.

    View full text