Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
Hypothesis: The reduction of dynamic hyperinflation and its negative effects on the
 respiratory system following a bronchodilator could lead to an improvement of cardiac
 function in terms of increased cardiac output. This may enhance oxygen delivery to the
 exercising muscles in COPD patients. Bronchodilator administration may also have an indirect
 effect on V'O2 kinetics via its action on cardiovascular and pulmonary variables.

 Objectives:

 1. To evaluate the effects of a bronchodilators on V'E , V'CO2 , and V'O2 kinetics in COPD
 during constant work-rate cycle exercise, and to evaluate whether bronchodilators will
 accelerate, indirectly, phase 2 kinetics (usually slower in COPD patients than normal
 subjects) and shorten t for V'E, V'CO2 , and V'O2 and shorten half-times for HR and O2
 pulse, thus showing an improvement of oxygen transport to the peripheral active muscles.

 2. To determine the impact of a bronchodilator-induced reduction in dynamic hyperinflation,
 and its effects on cardiovascular and pulmonary function, on exercise limitation in
 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.
Inclusion Criteria:

 -  40-80 years

 -  stable COPD

 -  FEV1 < 60 % predicted

 -  severe chronic breathlessness (Baseline Dyspnea Index < 6)

 Exclusion Criteria:

 -  SpO2 at rest < 90% or a a sustained decrease of > 4% in arterial O2 saturation during
 the ergometer test, as determined by pulse oximetry

 -  a body mass index (BMI) < 19 or > 30

 -  chronic oral steroid therapy

 -  other medical conditions which could cause or contribute to breathlessness, i.e.,
 heart disease or other respiratory diseases

 -  other problem which could interfere with carrying out of exercise testing, i.e.,
 neuromuscular diseases, orthopedic diseases, etc.