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.

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.