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Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
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Background: Obstructive Sleep Apnea (OSA) is the most common respiratory disorder during sleep. OSA is an independent risk factor for developing cardiovascular diseases (CVD). Although risk is increased, it is still challenging to identify which patients will develop CVD as standard disease metrics are not that helpful. Circulating biomarkers could be useful to risk stratify OSA patients. However, current evidence in this regard is limited. Oxidative stress biomarkers and cellular adhesion molecules might be particularly useful as these are elevated in OSA patients and in patients with CVD. Thesis Objectives: 1. Identify and summarize the existing evidence on prognostic biomarkers in OSA (Chapters 1-2).2. Evaluate the association between cellular adhesion molecules, oxidative stress markers and OSA (Chapters 3-4).3. Evaluate whether levels of cellular adhesion molecules and oxidative stress markers predict incident CV events in an OSA-cohort (Chapter 5-6).4. Discuss the implications and future directions of the findings (Chapter 7). Methods: Adult patients (>19 years old) referred for suspected OSA to the University of British Columbia Hospital Sleep Disorder Laboratory for inpatient polysomnography (PSG) were studied. Fasting blood (15 ml) was collected on the morning after PSG, and plasma was stored in a -80C freezer. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin (endothelial selectin) were assessed. Incidence of CV events was assessed by deterministic linkage through Popdata-BC. Results: OSA severity was independently associated with higher circulating E-selectin and 8-isoprostane levels. In patients with suspected OSA, ICAM-1 was an independent predictor of incident CV events (OR=4.12 95% CI 1.47-11.55). In moderate to severe OSA patients, E-selectin was independently associated with CV events (OR = 4.07 95% CI 1.06 – 15.61), but not in patients without OSA. Oxidative stress markers were not associated with incident CV events. Conclusion: E-selectin and 8-isoprostane were independently associated with OSA. Cellular adhesion molecules such as ICAM-1 and E-selectin were associated with incident CV events and might be promising markers in CV disease prediction in OSA. Oxidative stress markers were not associated with incidence of CV events.
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Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Introduction: With a reported prevalence of up to 5%, pediatric obstructive sleep apnea syndrome (OSAS) is a common childhood affliction. Consequences associated include growth delay, metabolic disturbance, impaired cognition, cardiovascular morbidity, and wake-time behaviour. Altered craniofacial morphology such as backwardly positioned jaws, small upper jaw/lower jaw ratios, and long narrow faces have been associated with pediatric OSAS. Standardized craniofacial digital photography is a readily available and safe imaging method that has been used in adult study populations; however, it has yet to be utilized in a pediatric population to assess its utility as a screening tool for OSAS. Objective: Utilizing a systematic clinical examination, the prevalence of altered craniofacial morphology in children referred for overnight polysomnography at BC Children’s Hospital will be assessed. Calibrated digital photographs will be analyzed to extrapolate any craniofacial findings associated with pediatric OSAS. Methods: Patients aged 4-16 were recruited at BCCH to participate, undergoing an extra-oral and intra-oral orthodontic exam, the taking of one frontal and one lateral photograph, and completion of a standardized sleep questionnaire by the Parent/Guardian. Results: 65 participants (29 female, 36 male, mean age 8.9 ± 3.1 years) were compared based on their AHI. 27 children had an AHI 5/h). 19/65 participants (29.2%) were obese, and excluded from final analysis. Of the 44 remaining children, no significant differences were found for any direct clinical measurements between children with and without OSAS. Analysis of the standardized craniofacial photographs revealed that children with OSAS had a more obtuse cervicomental angle (7° increase), and an increase in lateral facial height (6 mm increase). An increasing cervicomental angle, intercanthal distance and cricomental distance were all correlated with the severity of OSAS. Conclusion: Aside from increases in cervicomental angle and lateral facial height, this study suggests altered craniofacial morphology may not be significantly associated with pediatric OSAS. Standardized craniofacial photography, in particular the measure of cervicomental angle, shows promise as a potential screening tool for OSAS, but requires further research.
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Objectives: Obstructive Sleep Apnea prevalence is substantially higher in men and subjects with higher body mass indexed. OSA is present in 41% of individuals with a BMI>28 kg/m², and in up to 78% in morbidly obese patients. Obesity alone is not the sole cause of OSA and craniofacial morphology is also a key determinant of the predisposition to airway collapse. There is still controversial data on the craniofacial characteristics of obese OSA patients and we hypothesize that the age when individuals become obese, can affect the craniofacial features of obese OSA patients.Methods: The prospective sample consisted of 39 obese and 43 non-obese OSA adults matched for age and OSA severity from a retrospective cohort. The age of obesity onset was determined through a questionnaire and diagnosis of craniofacial and airway morphology was made from standard cephalometric radiographs.Result: Twelve early obese, 21 late obese and 29 non-obese OSA patients were deemed eligible for this study. The mean age was 45.6, 50.9 and 48.1 years for early, late and non-obese groups, respectively. Non-obese OSA, compared to obese subjects, showed a significantly more retrognathic mandible, larger maxillo-mandibular discrepancy, shorter lower facial height, deeper overbite, less upper incisors proclination and protrusion, longer soft palate, higher position of hyoid bone, narrower inferior airway space, longer airway length and less obtuse head posture. The early obesity group, compared to non-obese, showed a prognathic mandible, longer lower facial height, more proclined upper incisors, caudally positioned hyoid bone, wider inferior airway space and shorter airway length. The late obesity group, compared to non-obese group, showed a proclined and protrusive upper incisors, shallower overbite, inferiorly positioned hyoid bone, shorter airway length and obtuse cranio-cervical angle. There was no significant difference between early and late obesity groups. Conclusion: Obese OSA patients have more developed craniofacial skeletons with less bony and airway constriction than their non-obese counterparts; and early and late obesity groups showed discrepancies in their characteristics which were different from non-obese subjects, suggesting a possible impact of obesity onset on craniofacial characteristics. Further studies are still needed to determine the effect of obesity onset on craniofacial development.
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Objectives: Altered dentofacial morphology has been suggested as an etiology for childhood OSA. Nevertheless, existing reports on the dentofacial characteristics of children with OSA vary significantly and are limited by the infrequent use of polysomnography (PSG) for diagnosis. Therefore, the objective of this study is to establish the prevalence of dentofacial morphology in children with OSA diagnosed using PSG.Methods: The sample comprised 64 children between the ages of 4-16 who were referred to BC Children’s Hospital for PSG. Diagnosis of OSA was provided by an overnight, in-laboratory PSG. Malocclusion was assessed clinically by one orthodontist (K.L.), blinded to PSG results. Results: Children with previous orthodontic treatment were excluded and children with craniofacial syndromes were analyzed separately. The 17 patients with craniofacial syndromes presented a significantly different dentofacial features and higher prevalence of OSA when compared to the non-syndromic children. The remaining 39 patients were divided into an OSA group (AHI ≥ 2; n=17) and a non-OSA group (AHI
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Objective: The aim of this study was to evaluate the accuracy of three thermosensitive microsensors, which record “wear-time” of removable oral appliances (OA) used for orthodontics and obstructive sleep apnea therapy.Methods: In vitro testing was undertaken for TheraMon (Sensor T, n=20), AIR-AID SLEEP (Sensor A, n=30) and DentiTrac (Sensor D, n=16) microsensors, which were placed in a water bath to simulate “wear-time” of OA. Logs of when the microsensors were placed in the water bath were compared to the time readouts from the microsensors. Trial 1 examined the accuracy of long durations of “wear” (7 hours/day). Trial 2 examined short durations of “wear” (2 hour intervals). Trial 3 tested the impact of different embedding materials on accuracy: acrylic, polyvinylchloride and thermoactive acrylic. In vivo testing included 14 volunteers who wore maxillary retainers embedded with Sensor A and D for 30 nights. Subjects’ logs of appliance usage were compared to the computed readouts from the sensors. Results: In the in vitro phase, the median absolute deviation of the computed “wear-time” minus the logged time was 0.00 minutes for Sensor A and Sensor T in all trials. For Sensor D, the median deviation was 5.00 minutes in trial 1 and 3 and 10.00 minutes in trial 2. Sensor A was significantly more accurate than Sensor T and Sensor D in trial 1 (p
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