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

NCT ID: NCT00975403

Last Updated: 2012-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2012-09-30

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

mild COPD; dyspnea; exercise; respiratory mechanics; COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: TRIPLE

Study Groups

Dead space breathing

Group Type: EXPERIMENTAL

Dead space breathing

Intervention Type: DEVICE

Chemical loading by adding a deadspace (600ml) to the breathing circuit during a single cycle exercise test

Room air breathing

Group Type: SHAM_COMPARATOR

Room air breathing

Intervention Type: DEVICE

Sham comparator (vs deadspace) during a single cycle exercise test will entail breathing room air on the same circuit without the rebreathe valves

Interventions

Dead space breathing

Chemical loading by adding a deadspace (600ml) to the breathing circuit during a single cycle exercise test

Intervention Type: 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

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Canadian Lung Association

INDUSTRY

Sponsor Role: collaborator

Queen's University

OTHER

Sponsor Role: lead

Responsible Party

Dr. Denis O'Donnell

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Denis E O'Donnell, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Queen's University and Kingston General Hospital

Locations

Respiratory Investigation Unit, Kingston General Hospital

Kingston, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 23590271 (View on PubMed)

Other Identifiers

DSS15110

Identifier Type: -

Identifier Source: org_study_id