Bronchodilator Effect on O2 Deficit and V'O2 Kinetics During Moderate Intensity Exercise in Normoxemic COPD.

The inability to engage in the usual activities of daily living is one of the most distressing experiences of people afflicted with Chronic Obstructive Pulmonary Disease (COPD). Exercise intolerance progresses relentlessly as the disease advances and can lead to virtual immobility and social isolation. Our understanding of the complex interface between physiological impairment and disability in COPD has increased considerably in recent years. It has become clear that in COPD, exercise intolerance ultimately reflects integrated abnormalities of the ventilatory, cardiovascular, peripheral muscle and neurosensory systems. Ventilatory constraint is the dominant contributor to exercise limitation in more advanced disease. Recently, important studies have been conducted on the role of peripheral muscle dysfunction in exercise limitation in COPD.

The present study will test the hypothesis that the administration of bronchodilators (i.e., inhaled β2-agonist and inhaled anticholinergics in combination) in normoxemic COPD patients during moderate-intensity constant-load exercise may result in an enhancement of oxidative metabolism, reflected by reductions of O2 def and phase 2 tV'O2.

Fifteen normoxemic patients with stable COPD (FEV1 less than 60 % predicted) and severe chronic breathlessness (Baseline Dyspnea Index less than 6) will complete the study.

Each patient will perform three visits. At the first visit, patients will be familiarized with the various questionnaires and scales for rating the intensity and quality of symptoms and they will carry out pulmonary function testing and a symptom-limited incremental cycle exercise test in order to determine the anaerobic threshold (AT), the peak work-rate and the peak oxygen uptake. Each patient will subsequently complete two visits in which they will receive either nebulized bronchodilator (BD) (Combivent®, ipratropium 0.5 mg + salbutamol 2.5 mg) or placebo (PL), in random order. At 90-100 minutes post-dose, patients will perform pulmonary function tests, then they will perform a constant-load exercise test at 80% of AT V'O2. During constant-load exercise tests (2nd and 3rd visit), small samples of blood from the earlobe of each subject will be collected in order to determine the level of lactate and breathing gases (oxygen and carbon dioxide) in the blood.