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

NCT00975403 | Completed

• 1 other identifier: DSS15110
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Dyspnea intensity measured by the 10-point Borg scale during cycle exercise

  Standardized time during exercise

Secondary Outcomes (1)

• Cycle exercise endurance time

  During exercise testing at study visits

Study Arms (2)

Dead space breathing

EXPERIMENTAL

Device: Dead space breathing

Room air breathing

SHAM COMPARATOR

Device: Room air breathing

Interventions

Dead space breathing DEVICE

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

Dead space breathing

Room air breathing DEVICE

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

Room air breathing

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Queen's University: lead
• Canadian Lung Association: collaborator

Study Sites (1)

Respiratory Investigation Unit, Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (1)

• 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.

  PMID: 23590271 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Dyspnea; Motor Activity

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Behavior

Study Officials

• Denis E O'Donnell, MD, FRCPC

  Queen's University and Kingston General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 10, 2009
• First Posted: September 11, 2009
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 17, 2012

Record last verified: 2012-12

Locations

CA (1)