Pathophysiological Mechanisms of Dyspnea and Activity-limitation in Mild Chronic Obstructive Pulmonary Disease (COPD)

Pathophysiological Mechanisms of Dyspnea and Activity-Limitation in Mild COPD

Chronic obstructive pulmonary disease (COPD) is a growing cause of death, disability and health care costs in Canada. Nevertheless, COPD remains largely under-diagnosed and under-treated, particularly in its early stages. Patients with mild COPD have variable respiratory symptoms and often go unrecognized by their caregivers. Recent studies indicate that even smokers with near normal breathing test results can have extensive small airway disease/dysfunction at rest, which becomes more pronounced during the stress of exercise thus leading to unpleasant breathing difficulty. This study seeks to better understand the nature and causes of breathing discomfort and activity limitation in a group of patients with mild COPD. The investigators will compare detailed tests of small airway function and conduct an evaluation of several key physiological parameters during the stress of exercise in patients with mild COPD and in healthy, age-matched, non-smoking control subjects. The investigators will also compare detailed physiological responses to exercise under conditions of chemical loading and mechanical unloading of the respiratory system in patients with mild COPD.

The proposed study will be the first to systematically test the hypothesis that pathophysiological abnormalities in ventilatory demand, pulmonary gas exchange, small airway function, dynamic ventilatory mechanics and respiratory muscle function contribute significantly to exertional dyspnea and activity-limitation in patients with mild COPD. This study will be the first to determine if these abnormalities can be manipulated.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: Dead space breathing; Device: Room air breathing

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Respiratory Investigation Unit, Kingston General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Post-bronchodilator forced expiratory volume in 1 sec (FEV1) ≥ 80%predicted and a FEV1/forced vital capacity (FVC) ratio < 0.70;
• Clinically stable as defined by no changes in medication dosage or frequency of administration with no exacerbations or hospitalizations in the preceding 6 weeks;
• A cigarette smoking history ≥ 20 pack-yrs;
• Body mass index between 18.5 and 30 kg/m2;
• Able to perform all study procedures and provide informed consent.

Exclusion Criteria:

• A diffusing capacity of the lung for carbon monoxide (DLCO) < 40 %predicted;
• Presence of active cardiopulmonary disease (or comorbidities) other than COPD that could contribute to dyspnea and exercise limitation;
• Clinical diagnosis of sleep disordered breathing;
• History or clinical evidence of asthma;
• Presence of important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s);
• Use of daytime oxygen or exercise-induced arterial oxygen desaturation to <80% on room air.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dead space breathing	Device: Dead space breathing; Chemical loading by adding a deadspace (600ml) to the breathing circuit during a single cycle exercise test
Sham Comparator: Room air breathing	Device: Room air breathing; Sham comparator (vs deadspace) during a single cycle exercise test will entail breathing room air on the same circuit without the rebreathe valves

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dyspnea intensity measured by the 10-point Borg scale during cycle exercise	Standardized time during exercise

Secondary Outcome Measures

Outcome Measure	Time Frame
Cycle exercise endurance time	During exercise testing at study visits

Collaborators and Investigators

• Sponsor: Queen's University
• Collaborators: Canadian Lung Association
• Investigators: Principal Investigator: Denis E O'Donnell, MD, FRCPC, Queen's University and Kingston General Hospital

Publications and helpful links

General Publications

• Chin RC, Guenette JA, Cheng S, Raghavan N, Amornputtisathaporn N, Cortes-Telles A, Webb KA, O'Donnell DE. Does the respiratory system limit exercise in mild chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2013 Jun 15;187(12):1315-23. doi: 10.1164/rccm.201211-1970OC.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 14, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: exercise; COPD; respiratory mechanics; mild COPD; dyspnea
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea
• Other Study ID Numbers: DSS15110