Description

The Purpose of the Study:

The aim of the proposed study is to examine whether regular microdoses of low intensity physical activity (PA) can reduce the vascular dysfunction and adverse cardiovascular consequences associated with being sedentary in patients with COPD.

Hypothesis to be Tested:

Primary Hypothesis: Endothelial function (measured as superficial femoral flow mediated dilation) will be reduced in patients with COPD after 3-hours of prolonged sitting compared to the same duration of sitting interspersed with micro-doses of PA (5 min/hour of walking).

Secondary Hypothesis: Superficial femoral endothelial shear rate and antegrade blood flow will be reduced and retrograde blood flow and arterial stiffness will be increased following prolonged sitting compared to the same duration of sitting interspersed with micro-doses of PA. Mean 24-hour blood pressure will be lower when micro-doses of PA are used to reduce sedentary time.

Exploratory Hypothesis: There will be an increased release of endothelial microparticles (EMP) following prolonged sitting compared to the same duration of sitting interspersed with micro-doses of PA. Furthermore, femoral artery blood antegrade blood flow and shear rate will progressively decline, while retrograde blood flow will increase over each 30 minutes of sitting, but not when regular micro-doses of PA are performed. Flow mediated dilation will progressively decline and (EMP) release will progressively increase with each hour of sitting but not when regular micro-doses of PA are performed.

Justification: The benefits of performing regular moderate-to-vigorous intensity physical activity are well known and are associated with a lower incidence of cardio-metabolic disorders. Patients with chronic obstructive pulmonary disease generally engage in very little moderate to vigorous PA due to exertional dyspnea and typically spend a large portion of each day sitting, reclining or lying down. This increase in sedentary behaviour has been associated with vascular dysfunction, elevated blood pressure and greater risk of cardiovascular mortality in patients with COPD. As sedentary behaviour results in low global blood flow, it is an attractive postulate that one of the detrimental effects of reduced PA may be related to low vascular shear stress. More specifically, reduced shear stress has been documented to impair vascular endothelial function, promote adverse blood flow patterns (i.e. increased retrograde and reduced antegrade flow), increase vascular tone, elevate blood pressure and increase pro-atherosclerotic mediators (i.e. increased circulating levels of endothelial microparticles [EMPs] that are established markers of a dysfunctional and diseased endothelium). Growing evidence suggests that even lower intensity PA or just breaking up sedentary time may have significant health benefits. More specifically, it is feasible that increased blood flow and enhanced shear stress that occurs by moving may have a variety of cardiovascular benefits. Whether reducing sedentary time with regular short bouts (micro-doses) of low intensity PA can offset the adverse vascular consequences of prolonged sedentary behaviour in patients with COPD has not been studied.

Study Design: The study will be performed using a prospective randomized crossover design with subjects acting as their own control. After obtaining informed consent, the first visit will consist of a pulmonary function test to confirm the severity of airflow obstruction. To document current PA levels of subjects and to ensure consistency in PA between the two experimental trials, subjects will be given an accelerometer to measure their habitual physical activity levels and sedentary time on the 5 days before, and on the day of, each experimental trial. Visits 2 and 3 will then be randomized to either: 1) control - sedentary behaviour (either sitting or reclining) for 3 hours or 2) micro-doses - sedentary behavior for 3 hours with 5 minutes of walking every hour. Each visit will be separated by at least 6 days. For 24-hours before, diet will be standardized and patients will be asked to refrain from moderate-to-vigorous PA, alcohol and caffeine. Patients will come fasted (>8hr) for each visit and blood samples and vascular measurements will be made at baseline, and at 1, 2 and 3 hours of prolonged sitting. To further assess blood vessel health 24 hour ambulatory blood pressure measurements will be made following the first vascular assessment at 9am. Statistical Analysis : Data will be assessed for normalcy using a Shapiro-Wilk test. Primary and secondary outcome variables will be analyzed using linear mixed models, with repeated measures of condition (control vs. micro doses) and time (baseline vs post) as fixed factors. If significant interactions are found a Tukey post-hoc analysis will be used. The alpha level for all analysis will be set at 0.05. For the time course data linear mixed models, with repeated measures of condition (control vs. micro doses) and time (0, 1, 2, 3 hours) as fixed factors. Additionally, to assess differences between control and microdoses of PA for mean daytime, night time and nocturnal dipping blood pressures dependent t tests will be used.

        Non-smoking (>6 months) patients with stable moderate-to-severe COPD (post bronchodilator
        forced expired volume in 1 sec/forced vital capacity<0.7 and <lower limit of normal,
        30%<Forced Expired Volume in 1 sec<80% predicted and exacerbation free for >6 weeks) will
        be recruited for the study.
        Exclusion Criteria:
          1. performing structured exercise training (or pulmonary rehabilitation)
          2. have a history of deep vein thrombosis
          3. are on anticoagulant medication
          4. have advanced cardiac or cerebrovascular disease (i.e. heart failure, previous stroke
             or myocardial infarction)
          5. have diabetes
          6. have musculoskeletal contraindications that limit their ability to perform physical
             activity
          7. vascular ultrasound measurements cannot be obtained.