The continuum of physiological impairment during treadmill walking in patients with mild-to-moderate COPD: patient characterization phase of a randomized clinical trial

PLoS One. 2014 May 1;9(5):e96574. doi: 10.1371/journal.pone.0096574. eCollection 2014.

Abstract

Background: To have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.

Methods: Data were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study. Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise. All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.

Results: Chronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104). Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups. Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001). Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls. Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).

Conclusions: Lower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort. Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.

Trial registration: ClinicalTrials.gov: NCT01072396.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cross-Over Studies
  • Double-Blind Method
  • Dyspnea / etiology*
  • Dyspnea / physiopathology
  • Exercise Test / adverse effects*
  • Exercise Tolerance
  • Female
  • Forced Expiratory Volume / physiology*
  • Humans
  • Leg / physiopathology*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Disease, Chronic Obstructive / physiopathology

Associated data

  • ClinicalTrials.gov/NCT01072396

Grants and funding

This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) and Pfizer Inc. Writing, editorial support, and formatting assistance was provided by Jane M. Gilbert, BSc CMPP, of Envision Scientific Solutions, which was contracted, and compensated by BIPI and Pfizer Inc for these services. The funders provided support in the form of salaries for authors QD, HAP, FCA, & AI but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.