STRUCTURAL AND FUNCTIONAL CORRELATES OF EXERCISE VENTILATORY INEFFICIENCY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS WITH MILD-TO-MODERATE SPIROMETRIC ABNORMALITIES

Background: Individuals with chronic obstructive pulmonary disease (COPD) have higher than normal ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise. There is growing evidence that emphysema on thoracic computed tomography (CT) scans is associated with poor exercise capacity in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that emphysema is an underlying cause of microvascular dysfunction and ventilatory inefficiency, which in turn contributes to reduced exercise capacity. We expected ventilatory inefficiency to be associated with a) the extent of emphysema; b) lower diffusing capacity for carbon monoxide; c) a reduced pulmonary blood flow response to exercise; and d) reduced exercise capacity. Methods: In a cross-sectional study, 19 subjects with mild-to-moderate COPD (mean ± SD FEV1= 82 ± 13% predicted, 12 GOLD grade 1) and 26 age-, sex-, and activity-matched controls underwent a ramp-incremental symptom-limited exercise test on a cycle ergometer. Ventilatory inefficiency was assessed by the minimum VE/VCO2 value (nadir). A subset of subjects also completed repeated constant work rate exercise bouts with non-invasive measurements of pulmonary blood flow. Emphysema was quantified as the percentage of attenuation areas below -950 Housefield Units on CT scans. An electronic scoresheet was used to keep track of emphysema sub-types. Results: COPD subjects typically had centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/lower lobe ratio= 0.82 ± 0.04). They had lower peak oxygen uptake (VO2), higher VE/VCO2 nadir and greater dyspnea scores than controls (p<0.05). Lower peak O2 and worse dyspnea were found in COPD subjects with VE/VCO2 nadirs ≥ 30. COPD subjects had blunted increases in pulmonary blood flow from rest to iso-VO2 exercise (p<0.05). Higher VE/VCO2 nadir in COPD subjects correlated with emphysema severity (r= 0.63), which in turn correlated with reduced lung diffusing capacity (r= -0.72) and blunted changes in pulmonary blood flow from rest to exercise (r= -0.69) (p<0.01). Conclusions: Ventilation “wasted” in emphysematous areas is associated with reduced exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (gas transfer) to a key clinical outcome (reduced exercise capacity) in COPD patients with modest spirometric abnormalities.

Shiftwork, sleep disturbance and the metabolic syndrome among female hospital workers

Background: Shiftwork is associated with increased sleep disturbance and cardiovascular and metabolic disease risk. This thesis will focus on shiftwork-related sleep disturbance and the potential mediating role of reduced sleep duration in the relationship between a current rotational shiftwork schedule and the metabolic syndrome among female hospital employees. Objectives: 1) To describe sleep patterns in relation to different shiftwork exposure metrics (current status, cumulative exposure, number of consecutive night shifts); 2) To assess the association between shiftwork metrics and sleep duration; 3) To determine whether sleep duration on work shifts mediates the relationship between a current rotational shiftwork pattern and the metabolic syndrome; and 4) To assess whether cumulative shiftwork exposure and the number of consecutive night shifts are associated with the metabolic syndrome. Methods: 294 female hospital employees (142 rotating shiftworkers, 152 dayworkers) participated in a cross-sectional study. Shiftwork parameters were determined through self-report. Sleep was measured for one week with the ActiGraph GT3X+, a tri-axial accelerometer. The metabolic syndrome was defined according to the Joint Interim Studies Consensus Statement. Sleep was described by shiftwork exposure parameters, and multivariable linear regression was used to determine associations between shiftwork variables and sleep duration. Regression path analysis was used to assess whether sleep duration was a mediator between a current shiftwork schedule and the metabolic syndrome, and the significance of the indirect (mediating) effect was tested with bootstrap confidence intervals. Logistic regression was used to determine associations between cumulative shiftwork exposure, number of consecutive night shifts, and the metabolic syndrome. Results: Current shiftworkers slept less on work shifts, more on free days, and were more likely to nap compared to dayworkers. Sleep duration on work shifts was a strong intermediate in the relationship between a current shiftwork pattern and the metabolic syndrome. Cumulative shiftwork exposure and the number of consecutive night shifts did not affect sleep or the metabolic syndrome. Conclusions: A current shiftwork pattern disrupts sleep, and reduced sleep duration is an important intermediate between shiftwork and the metabolic syndrome among female hospital employees.

Sleep Quality as a Mediator of the Relationship Between Attachment Anxiety and Health Outcomes During Romantic Conflict

Attachment anxiety, or a fear of abandonment by those close to you, is an important predictor of many individual and interpersonal outcomes. Individuals high in attachment anxiety are more likely to experience physical illness due to disrupted immune functioning and deregulated stress responses. I was interested in examining potential mechanisms accounting for why individuals high in attachment anxiety are more likely to become ill. One variable that has been demonstrated to mediate the relationship between stress and health is sleep quality. As attachment anxiety is characterized by the experience of stress and worry over abandonment by romantic partners, I predicted sleep quality would mediate the relationship between attachment anxiety and health. Further, I predicted attachment anxiety would interact with romantic threat, in that individuals high in attachment anxiety who perceive threat to their relationships would have poor sleep quality (compared with individuals low in attachment anxiety and individuals high in anxiety who do not perceive threat) which would mediate the most unhealthy outcomes. I tested these hypotheses using three online diary studies. In the first two studies, participants completed a seven-night diary describing their sleep quality, health, and interaction with their partner. In Study 3, I surveyed participants once a week for eight weeks to examine longer-term health outcomes. Sleep quality did indeed mediate the relationship between attachment anxiety and various health outcomes over one week (Study 2), and showed a trend towards mediating effects over two months (Study 3). Interestingly, however, attachment anxiety did not interact with perceived romantic threat to predict health in the mediation analyses. Implications for sleep as a mediating variable are discussed, as well as the lack of attachment anxiety by romantic threat interaction.