Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Combivent
Intervention type(s): Drug
Intervention description(s): Nebulized Combivent (4 mL) or saline solution (0.9% NaCl) (4 mL) will be administered once only to subjects.
Other intervention name(s): Ipratropium - Salbutamol
Intervention MeSH terms: Ipratropium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: COPD; Combivent; Exercise; Bronchodilator; Kinetics