The Effects of Aerobic Exercise Training on Vascular, Cardiac and Cerebral Vascular Function in COPD

Study Overview
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Brief Summary
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The primary cause of chronic obstructive pulmonary disease is smoking, which can lead to inflammation in the lungs and blood vessels that can lead to secondary problems such as blood vessel disease, high blood pressure and heart disease. Aerobic exercise training has been shown to reduce the risk of heart and brain disease; however, it is currently unknown whether exercise training can have the same affect in patients with COPD. The aim of this study is to investigate how eight weeks of aerobic exercise training improves blood vessel and heart function and brain blood flow in patients with COPD.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is a treatable respiratory condition that is only partially reversible. The primary cause of COPD is smoking which leads to airway inflammation and oxidative damage to the lungs, which has been linked to the development and progression of the disease. The inflammation is not isolated to the lungs as patients with COPD also have systemic inflammation that has been linked to a number of cardiovascular comorbidities such as endothelial dysfunction, cardiovascular disease and stroke. Evidence demonstrates that COPD patients have a greater incidence of vascular dysfunction and adverse vascular remodeling, which worsens with disease severity. In fact, patients with COPD are at 35 times greater risk of developing cardiovascular disease and stroke than healthy aged matched individuals. In healthy individuals and a number of chronic conditions, aerobic exercise training is well established to reduce the risk of cardiovascular and cerebrovascular disease. The benefits of exercise are likely through improvements in endothelial function, systemic inflammation, and cardiac and cerebral vascular function. However, whether exercise training can have the same effects in a chronic inflammatory condition like COPD has not been studied. The purpose of this study is to determine the effectiveness of an 8 week aerobic exercise training program in patient's chronic obstructive pulmonary disease as determined by improvements in endothelial function, systemic inflammation and cardiac and cerebral vascular function.

Official Title
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The Effects of Aerobic Exercise Training on Peripheral Vascular, Cardiac and Cerebral Vascular Function in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Other: Individualized, non-linear aerobic exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smokers (>6 months); Forced expiratory volume in one second/ forced vital capacity (FEV1/FVC) < 0.7 and FEV1/FVC <lower limit of normal Stable (>3 months exacerbation free) Exclusion Criteria: On supplemental oxygen; Known cardiac or cerebral vascular disease, diabetes, obstructive sleep apnea; Uncontrolled hypertension; BMI >30kg/m2 Currently performing pulmonary rehabilitation or structured exercise training; Desaturate during exercise (SpO2<85%) Cardiovascular contraindications to exercise in the incremental test used for screening

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with COPD<br>Stable patients with COPD participated in an 8-week (24 session) individualized, non-linear aerobic exercise training program consisting of upper and lower body cycle ergometry. | Other: Individualized, non-linear aerobic exercise training<br>* Aerobic exercise performed on lower body stationary ergometer and an upper extremity arm crank. Intensity (50-95% workload maximum) and durations (20-45 min) are fluctuated daily to optimize training stress and adaptation<br>|
| Active Comparator: Healthy Controls<br>Age, sex, BMI and activity matched controls participated in an 8-week (24 session) individualized, non-linear aerobic exercise training program consisting of upper and lower body cycle ergometry. | Other: Individualized, non-linear aerobic exercise training<br>* Aerobic exercise performed on lower body stationary ergometer and an upper extremity arm crank. Intensity (50-95% workload maximum) and durations (20-45 min) are fluctuated daily to optimize training stress and adaptation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | The change in brachial artery flow mediated dilation measured using reactive hyperaemia | 8-weeks (following 24 sessions of exercise training) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial Stiffness | The change in pulse wave velocity measured using tonometry | 8-weeks (following 24 sessions of exercise training) | 
| Carotid intima-medial thickness | The change in carotid intima-medial thickness measured by ultrasound | 8-weeks (following 24 sessions of exercise training) | 
| Carotid Compliance | The change in carotid compliance measured using tonometry and ultrasound for the carotid arteries | 8-weeks (following 24 sessions of exercise training) | 
| Inflammatory Biomarkers | The change in serum levels of CRP, IL-6, IL-10 and TNF-alpha measured using Luminex multiplex bead-based technology | 8-weeks (following 24 sessions of exercise training) | 
| Systolic function | The change in stroke volume using echocardiography | 8-weeks (following 24 sessions of exercise training) | 
| Diastolic function | The change in left ventricular end-diastolic volume using echocardiography | 8-weeks (following 24 sessions of exercise training) | 
| Cerebral Blood Flow | The change in cerebral and neck blood flow using ultrasound | 8-weeks (following 24 sessions of exercise training) | 
| Cerebrovascular Reactivity | The change in middle cerebral artery velocity in response to carbon dioxide | 8-weeks (following 24 sessions of exercise training) | 
| Cerebrovascular Autoregulation | The change in phase delay measured by transfer function analysis | 8-weeks (following 24 sessions of exercise training) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Exercise Training, Flow-Mediated Dilation, Arterial Stiffness, Echocardiography, Cerebrovascular Physiology