Lau Yin Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 58-79). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.IV / Abstract in Chinese --- p.VI / Abbreviations --- p.VIII / Introduction --- p.1 / Chapter 1.1 --- Prevalence of COPD and asthma in Hong Kong --- p.1 / Chapter 1.2 --- Players in pathogenesis of COPD --- p.2 / Chapter 1.3 --- Players in pathogenesis of asthma --- p.4 / Chapter 1.4 --- The use of exhaled breath condensate in previous studies --- p.6 / Chapter 1. 5 --- Brief overview of chemokines --- p.8 / Chapter 1.6 --- Objective of this study --- p.12 / Materials and methods --- p.14 / Chapter 2.1 --- Study population --- p.14 / Chapter 2.1.1 --- Patients with COPD and control subjects --- p.14 / Chapter 2.1.2 --- Patients with asthma and control subjects --- p.15 / Chapter 2.2 --- Lung function --- p.15 / Chapter 2.3 --- Dyspnoea score measurement of patients with COPD --- p.16 / Chapter 2.4 --- Classification of patients and asthma severity --- p.16 / Chapter 2.5 --- Skin prick test and blood tests --- p.16 / Chapter 2.6 --- Collection of exhaled breath condensate --- p.17 / Chapter 2.7 --- Measurement of constituent in EBC --- p.17 / Chapter 2.7.1 --- "Measurement of 8-isoprostane, MCP-1 and GROα in patients with COPD and the corresponding control subjects" --- p.17 / Chapter 2.7.2 --- Measurement of eotaxin and MDC of patients with asthma and the corresponding control subjects --- p.18 / Chapter 2.8 --- Reproducibility of exhaled breath constituent --- p.18 / Chapter 2.8.1 --- "Assessment of reproducibility of the exhaled MCP-1, GROα and8- isoprostane measurements" --- p.19 / Chapter 2.8.2 --- Assessment of reproducibility of the exhaled eotaxin and MDC measurement --- p.19 / Chapter 2.9 --- Statistical analysis --- p.19 / Results --- p.21 / Chapter 3.1 --- Patients with COPD and corresponding control subjects --- p.21 / Chapter 3.2 --- Patients with asthma and corresponding control subjects --- p.28 / Discussion --- p.36 / Chapter 4.1 --- "Exhaled 8-isoprostane, GRO-α and MCP-1 of patients with COPD and corresponding control subjects" --- p.36 / Chapter 4.2 --- Exhaled eotaxin and MDC from patients with asthma and corresponding control subjects --- p.43 / Chapter 4.3 --- Technical aspects of EBC assessment --- p.49 / Future prospect --- p.54 / Conclusion --- p.56 / References --- p.58 / Tables and Figures / Table 1. Demographics of the COPD and control subjects --- p.22 / Figure 1. The level of 8-isoprostane in the exhaled breath condensate of COPD and control subjects --- p.23 / Figure 2. The level of GROa in the exhaled breath condensate of COPD and control subjects --- p.25 / "Figure 3 Bland and Altman's Plot of the repeatability of 8-isoprostane, GROa and MCP-1 in the exhaled breath condensate of normal controls" --- p.27 / Table2. Clinical and physiological details of the subjects --- p.29 / Figure 4. Level of eotaxin in exhaled breath condensate of asthma and control subjects --- p.30 / Figure 5 Level of MDC in exhaled breath condensate of asthma and control subjects --- p.31 / Table 3. Levels of eotaxin and MDC in exhaled breath condensate of asthma subjects on different dose of inhaled corticosteroids --- p.33 / Figure 6. Relationship between exhaled breath condensate level of MDC and total serum IgE level --- p.35

Les maladies chroniques impliquant le système respiratoire nécessitent un suivi sur la durée. L’activité physique et les paramètres cardiovasculaires sont essentiels pour ces pathologies. Nous nous sommes intéressés en particulier à la BPCO et à l’apnée obstructive du sommeil. La BPCO est caractérisée par un cercle vicieux d’inactivité : une gêne respiratoire entraîne une diminution de l’activité, qui elle-même augmente la gêne respiratoire par désentraînement. Le monitoring de l’activité, en lien avec la SpO2 est donc essentiel pour cette pathologie. Les désaturations nocturnes sont un paramètre cardinal de l’apnée du sommeil. Un actimètre permet d’évaluer la qualité du sommeil, complétant ainsi le suivi de cette pathologie. De plus, l’activité diurne est un indicateur de l’asthénie provoquée par le syndrome. Le but de ce travail a donc été la mise au point d’un actimètre communicant, capable de mesurer l’activité diurne, d’évaluer le temps de sommeil et de s’interfacer avec un oxymètre de pouls pour synchroniser la collecte de données. À partir des données récoltées durant 26 jours d’enRégistrements, nous avons mis au point et évalué un algorithme permettant de mesurer le temps passé assis, debout et allongé. Cet algorithme a été conçu pour être embarqué dans un microcontrôleur, ayant des ressources de calcul limitées. Nous avons également proposé un algorithme de détection des pas, dont le fonctionnement a été validé sur plus de 5 heures de marche, sur 22 patients différents, contre un comptage manuel. Nous avons enfin proposé une méthode de détection des transitions assis-debout pour l’instrumentation du test de levers de chaise de 3 minutes. Lors de l’analyse nocturne, nous avons mis au point un algorithme de détection du temps de sommeil, testé sur 25 nuits. Nous avons également proposé une méthode d’analyse de l’onde de pouls permettant d’extraire le rapport LF/HF de la variabilité cardiaque, permettant de détecter le sommeil paradoxal. Nous avons montré le résultat de l’agrégation des différentes données acquises par le système formé de l’actimètre et de l’oxymètre lors d’une nuit d’examen, comme outils à disposition du praticien. L’actimètre mis au point dans le cadre de ces travaux et les méthodes d’analyse du signal associées sont adaptés au suivi non invasif de pathologies respiratoires. Ils peuvent également être intégrés à un système de télémédecine via une passerelle informatique pour un suivi de long terme. / Chronic diseases affecting the respiratory system require a long-term monitoring. Physical activity and cardiovascular parameters are essential in those pathologies. We focused on two of those diseases : COPD and obstructive sleep apnea. COPD is characterized by a downward cycle of inactivity : a respiratory impairment leads to a reduction of activity, whose in turn worsen the respiratory impairment by a conditioning loss. As a consequence, activity monitoring and SpO2 are essential for the monitoring of this pathology. Nocturnal oxygen desaturation are a main feature of sleep apnea. An actimeter allows for sleep quality evaluation, and is a logical choice for a complementary measure of this disease. Moreover, diurnal activity is an indicator of the degree of physical weakness that can occur as a consequence of sleep apnea. The main goal of the work has been the developement of a connected actimeter, able to monitor diurnal activity, estimate the duration of sleep and collect data from a pulse oximeter to synchronise the data. From 26 days of accelerometric measures, we designed and validated an algorithm that compute the time spend sitting, standing and lying. This algorithm has been designed to be embedded in a microcontroler with limited computing power. We also proposed a step detection algorithm validated on 5 hours of walking, on 22 different patients, against a visual count. Finally, we designed a method to detect the sitting-standing change of posture to monitor the 3-minutes chair stand test. On the nocturnal aspect, we designed an algorithm used to estimate the sleep duration during a night. It as been tested on 25 nights. We also proposed a pulse wave analysis method to extract the LF/HF ratio of cardiac variability, to detect REM sleep. We showed the result of the aggregation of the different parameters collected by the system composed of the actimeter and the oximeter during a monitored night, as a tool to the healthcare professional. The actimeter design in the context of this work and the associated signal processing methods are appropriate to the monitoring of respiratory pathologies with a light equipment. They also can be integrated into a telemedecine system through a gateway computer, allowing for a long-term monitoring.

Le syndrome d’apnées obstructives du sommeil (SAOS) est associé à de nombreuses co-morbidités métaboliques et cardiovasculaires. L’hypoxie intermittente chronique, une des composantes du SAOS, induit des mécanismes intermédiaires délétères tels que stress oxydatif, inflammation, insulino-résistance ou encore dyslipidémie, à l’origine de ces comorbidités. Ces mécanismes intermédiaires sont également communs à d’autres pathologies respiratoires chroniques telles que la bronchopneumopathie chronique obstructive (BPCO) et le syndrome d’obésité hypoventilation (SOH).L’hypoxie intermittente et les mécanismes intermédiaires associés sont aussi à l’origine de l’existence et de la progression de la stéatopathie métabolique (« non alcoholic fatty liver disease »). Ce lien entre pathologies respiratoires chroniques et atteinte hépatique est un mécanisme essentiel mais plus récemment étudié des co-morbidités dans le SAOS et la BPCO. Différents biomarqueurs cardiométaboliques ont donc été étudiés dans ces pathologies respiratoires chroniques à la fois pour caractériser les co-morbidités et l’atteinte systémique et pour apprécier l’impact de différentes thérapeutiques. La première partie de cette thèse sera consacrée à une revue systématique des différents biomarqueurs cardio-métaboliques liés à chacune de ces 3 pathologies respiratoires chroniques : SAOS, BPCO et SOH.Le traitement du SAOS par pression positive continue (PPC) a un effet bénéfique sur les symptômes fonctionnels liés à cette pathologie. Cependant, l’impact de la PPC sur d’autres conséquences cardio-métaboliques délétères du SAOS reste encore à démontrer par des essais randomisés contrôlés, notamment sur l’atteinte hépatique.Dans la seconde partie de cette thèse, nous détaillerons l’impact de la PPC sur les différents marqueurs cardiométaboliques du SAOS à l’aide d’une revue systématique puis d’une étude randomisée contrôlée sur l’impact de la PPC sur les marqueurs d’atteinte hépatique.Par ailleurs, les patients atteints de SAOS, BPCO ou SOH reçoivent du fait de leur polypathologie (multimorbidité) des traitements médicamenteux multiples qui visent à contrôler au mieux les co-morbidités. Il est donc primordial de considérer la prise en charge globale de ces patients du point de vue de leurs traitements instrumentaux (PPC et ventilation non invasive) mais aussi en considérant l’impact des traitements médicamenteux associés. En effet, les traitements médicamenteux peuvent interférer avec la sévérité de la pathologie elle-même et impacter les biomarqueurs liés aux comorbidités associées. La troisième partie de cette thèse sera consacrée à l’étude d’un antihypertenseur chez le patient SAOS et envisagera l’influence des médicaments sur la pertinence de l’usage des bicarbonates comme marqueurs diagnostiques du SOH.En conclusion, nous insisterons sur la nécessité d’une prise en charge intégrée multi systémique et d’une prise en charge personnalisée de ces patients. / Obstructive sleep apnea (OSA) is associated with related metabolic and cardiovascular comorbidities. Chronic intermittent hypoxia the hallmark of OSA induces deleterious intermediary mechanisms such as oxidative stress, systemic inflammation, insulin resistance and dyslipidemia. Cardiovascular and metabolic comorbidities are also key features of other chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Chronic hypoxia and deleterious intermediary mechanisms also trigger occurrence and progression of non alcoholic fatty liver disease. This link between chronic respiratory diseases and liver injury is observed through modifications of specific liver biomarkers in OSA and COPD. A variety of cardiometabolic biomarkers have been studied for stratification of cardio-metabolic risk and assessing treatment impact in chronic respiratory diseases. The first part of this PhD thesis is a systematic review of cardio-metabolic biomarkers in 3 respiratory diseases: OSA, COPD and OHS.Continuous positive airway pressure (CPAP) the first line therapy for OSA improves symptoms and quality of life. However, CPAP effects on cardio-metabolic consequences remains still debated. In the second part of the PhD thesis, we will address CPAP impact on different cardiometabolic biomarkers and more specifically in markers of liver injury by reporting original results of a randomized controlled trial (RCT).Polypharmacy is usual in patients with OSA, COPD or OHS. Beyond CPAP or non invasive ventilation treatment, it is essential address the contribution of associated medications. Indeed, pharmacological treatments can interfere with the severity of the disease and control of associated comorbidities. The third part of the thesis will present a RCT evaluating Bosentan in hypertensive OSA patients and will present how medications for comorbidities decrease bicarbonate diagnosis value for OHS.We will conclude by underlining the crucial importance of personalized medicine and integrated care in chronic respiratory diseases.

Objectifs : L’objectif principal de cette étude est d’établir si la santé parodontale des femmes enceintes ayant un DG est moindre que celle des femmes enceintes sans DG. L’objectif secondaire est d’évaluer l’association entre la fréquence et l’intensité du ronflement avec la santé parodontale chez les femmes enceintes ayant un DG. Méthodologie : Une étude de type cas-contrôle a été conduite parmi des femmes enceintes suivies au CHU Sainte-Justine. Le diagnostic de DG a été recueilli dans le dossier médical des participantes. Le volet 1 de l’étude incluait des mesures autorapportées par des questionnaires. Un sous-groupe de femmes enceintes était ensuite invité au volet 2 qui incluait un examen buccal permettant d’évaluer la santé parodontale des participantes. Les associations entre le DG et le ronflement, l’apnée obstructive du sommeil (AOS) et les maladies parodontales ont été évaluées à l’aide d’analyses bivariées. Résultats : Douze femmes enceintes avec DG et 85 femmes enceintes sans DG ont rempli les questionnaires du volet 1. De ces femmes, trois avec DG et sept sans DG ont participé au volet 2. Les femmes enceintes avec le DG étaient moins nombreuses à travailler à temps plein (p=0.032), avaient un revenu individuel (p=0.039) et familial (p=0.050) plus faible, faisaient moins d’activité physique (p=0.004) et allaient moins chez le dentiste (p=0.002) que les femmes enceintes sans DG. Il n’y avait pas de différence statistiquement significative entre les deux groupes pour le ronflement, l’AOS et les maladies parodontales. Conclusions : Les résultats préliminaires de l’étude n’ont pas établi si la santé parodontale des femmes enceintes avec DG est moindre ni démontré une association avec les troubles respiratoires obstructifs du sommeil. Pour atteindre les objectifs de l’étude, l’augmentation de la taille d’échantillon prévue à n=200 est requise. / Introduction Gestational diabetes mellitus (GDM) affects one in six pregnancies worldwide. Several short- and long-term complications affecting the mother and child can result from GDM. A few studies have shown a positive association between periodontal disease and GDM. Periodontal disease is also associated with adverse effects on pregnancy. In addition to potentially affecting fetal health and maternal insulin resistance, periodontal diseases are associated with obstructive sleep-disordered breathing. However, the relationship between these two entities in the context of GDM has not yet been studied. Objectives: The primary objective of this study is to establish whether the periodontal health of pregnant women with GDM is less than the one of pregnant women without GDM. The secondary objective is to assess the association between snoring frequency and intensity with periodontal health in pregnant women with GDM. Methodology: A case-control study was conducted among pregnant women followed at Sainte-Justine Hospital. The diagnosis of GDM was collected from the participants' medical records. The first phase of the study included self-reported measures by questionnaires. A subgroup of pregnant women was then invited to a second clinical phase. This included an oral examination to assess the participants' periodontal health. The associations between GDM and snoring, obstructive sleep apnea (OSA), and periodontal disease were evaluated using bivariate analyses. Results: Twelve pregnant women with GDM and 85 pregnant women without GDM completed the questionnaires in the first phase of the study. Of these women, three with GDM and seven without GDM participated in the second phase. Pregnant women with GDM worked less full-time (p=0.032), had lower individual (p=0.039) and family (p=0.050) income, engaged in less physical activity (p=0.004), and went to the dentist less often (p=0.002) than pregnant women without GDM. There was no statistically significant difference between the two groups for snoring, OSA and periodontal disease. Conclusions: Preliminary results of the study did not establish whether periodontal health in pregnant women with GDM is poorer, nor did they demonstrate an association with obstructive sleep-disordered breathing. To achieve the study objectives, the increase in sample size to n=200 is required.

Thesis (PhD (Sport Science))--Stellenbosch University, 2008. / The benefits of exercise training for patients with chronic obstructive pulmonary disease (COPD) are well-documented. In South Africa, exercise programmes for COPD patients are limited and often expensive and inaccessible to the broader community. The purpose of this study was to assess the responses of COPD patients to an exercise programme and to determine if the same results can be obtained through a less costly programme. In the primary programme of the study, 22 subjects were subjected to 12 weeks of exercise training. Each subject underwent comprehensive pre- and post-intervention assessments, which included the measurement of overall health status by a physician, level of dyspnoea, forced expiratory lung function, exercise capacity, body mass index and health-related quality of life. Exercise sessions included aerobic and strength training exercises and involved three, hour-long exercise sessions a week. In the modified programme, 18 subjects were randomly divided into an experimental and control group. Eleven subjects were included in the experimental group and seven subjects in the control group. Subjects had to complete 32, hour-long exercise sessions in a 10-week period. The experimental group’s exercise programme was adapted so that no specialised equipment was used, while the control group exercised in a well-equipped exercise- and rehabilitation centre.

Thesis (MScSportSc)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: The purpose of the study was to measure the responses of chronic obstructive pulmonary disease patients to an exercise programme in a South Africa setting. Nine subjects were evaluated before and after aerobic and resistance training three times a week for the total of 12 weeks. Each evaluation measured forced expiratory lung function; health-related quality of life; functional capacity; level of dyspnea; body composition; physician global evaluation; and the patient global evaluation. The exercise programme consisted of one-hour exercise sessions, three times a week for 12 weeks. The exercise sessions included elements of aerobic and resistance training of the upper and lower extremities. Functional capacity improved drastically (p < 0.01), as did the physician and the patient global evaluations (p < 0.01 and p < 0.01, respectively). Levels of dyspnea also improved (p < 0.01). Health-related quality of life improved marginally (p = 0.03). No significant change was noted in lung function and body composition. The study concluded that an exercise programme consisting of aerobic and resistance training improves chronic obstructive pulmonary disease patients' health-related quality of life, functional capacity and levels of dyspnea. Exercise also reduces the symptoms of chronic obstructive pulmonary disease as are perceived by the physician and patient alike. Exercise does not change lung function or body composition of chronic obstructive pulmonary disease patients. Exercise in conjunction with appropriate medical treatment has the potential to benefit all chronic obstructive patients in South Africa. Keywords: COPD, quality oflife, functional capacity, rehabilitation, exercise. / AFRIKAANSE OPSOMMING: Die doel van die studie was om die reaksies te meet van pasiënte met chroniese obstruktiewe pulmonêre siekte op 'n oefenprogram in 'n Suid-Afrikaanse konteks. Nege proefpersone is voor en na aërobiese en weerstandsoefening drie keer per week vir 'n totaal van 12 weke geëvalueer. Elke evaluering het die volgende gemeet: geforseerde ekspiratoriese longfunksie, gesondheidsverwante lewenskwalitiet, funksionele kapasiteit; dispneevlak, liggaamsamestelling; geneesheer algehele evaluering asook pasiënt algehele evaluering. Die oefenprogram het uit een-uur sessies bestaan, wat drie keer per week vir 12 weke plaasgevind het. Die oefensessies het elemente van aërobiese en weerstandsoefeninge van die boonste en onderste ledemate ingesluit. Funksionele kapasiteit het drasties verbeter (p < 0.01), net so ook die geneesheer en pasiënt algehele evaluerings (p < 0.01 en p < 0.01, respektiewelik). Dispneevlakke het ook verbeter (p < 0.01). Gesondheidsverwante lewenskwaliteit het marginaal verbeter (p = 0.03). Geen beduidende veranderinge is in die longfunksie en liggaamsamestelling gevind nie. Die studie het bevind dat 'n oefenprogram wat uit aërobiese en weerstandsoefening bestaan gesondheidsverwante lewenskwaliteit, funksionele kapasiteit asook dispneevlakke van pasiënte met chroniese obstruktiewe pulmonêre siekte verbeter. Oefening verminder ook die simptome van chroniese obstruktiewe pulmonêre siekte soos waargeneem deur beide die geneesheer en pasiënt. Oefening verander ook nie longfunksie of liggaamsamestelling van pasiënte met chroniese obstruktiewe pulmonêre siekte nie. Oefening tesame met die geskikte mediese behandeling kan voordelig wees vir chronies obstruktiewe pasiënte in Suid- Afrika. Keywords: KOPS, lewenskwaliteit, funksionele kapasiteit, rehabilitasie, oefening.

Introduction. Les mécanismes physiopathologiques du remodelage vasculaire pulmonaire chez le patient BPCO sont encore mal élucidés. L'inflammation pourrait jouer un rôle déterminant.Objectifs. Déterminer le rôle de l'interleukine 6 (IL6) dans la physiopathologie de l'hypertension pulmonaire (HTP) associée à la BPCO.Méthodes. Nous avons étudié le lien entre l'IL6 et l'HTP sur une population de patients atteints de BPCO, l'effet de l'hypoxie sur le développement d'une HTP chez des souris IL6-/- et l'effet in vitro de l'IL6 sur les cellules endothéliales et les cellules musculaires lisses d'artère pulmonaire humaine.Résultats. Les patients BPCO avec HTP présentaient un taux plasmatique d'IL6 circulante plus élevé. Le génotype GG de l'IL6 était corrélé à un risque plus élevé de développer une HTP. L'IL6 est produite par tous les acteurs cellulaires impliqués dans la physiopathologie du remodelage vasculaire pulmonaire et en particulier la cellule musculaire lisse. Sa synthèse, ainsi que celle de ses récepteurs, est très nettement stimulée par l'hypoxie aigue et chronique. L'IL6 participe probablement à l'entretien de la dysfonction endothéliale, à la migration des cellules musculaires lisses et au recrutement des cellules inflammatoires. Les souris IL6-/- sont partiellement protégées de l'hypertension pulmonaire hypoxique et présentent un moindre recrutement pulmonaire de cellules inflammatoires induit par l'hypoxie. Le taux d'IL6 est corrélé à une longueur télomérique plus courte chez les patients BPCO, témoignant d'un processus de vieillissement biologique accéléré. L'HTP associée à la BPCO ou à l'hypoxie chronique pourrait résulter d'une accentuation du processus de sénescence des cellules vasculaires pulmonaires, favorisé par l'inflammation.Conclusion. L'inflammation et plus particulièrement l'IL6 semblent fortement impliquées dans la physiopathologie du remodelage vasculaire pulmonaire chez le patient BPCO. / Introduction. The pathophysiological mechanisms responsible for pulmonary vascular remodeling in COPD remain poorly understood. Inflammation may play a major role.Objectives. To study the role of interleukin-6 (IL6) in the pathophysiology of pulmonary hypertension associated with COPD.Methods. We studied the relationship between IL6 and PH in a population of patients with COPD, the effect of hypoxia on the development of PH in mice IL6-/- and the effect of IL-6 on endothelial cells and smooth muscle cells of human pulmonary artery in vitro.Results. COPD patients with PH were characaterised by a more pronounced hypoxia and higher plasma levels of circulating IL-6. The GG genotype of IL-6 also correlated with a higher risk of developing PH in these patients. Each of the different cellular elements that promote pulmonary vascular remodeling are known to produce IL-6, with smooth muscle cells known to be a particularly important source of this cytokine In addition, synthesis of IL-6 and its associated receptors is increased in response to acute and chronic hypoxia. It is likely that IL-6 contributes to endothelial dysfunction, the migration and, indirectly, proliferation of smooth muscle cells, and recruitment of inflammatory cells. Indeed, IL6-/- mice are partially protected from hypoxia-associated pulmonary hypertension and demonstrate attenuated hypoxia-induced lung recruitment of inflammatory cells. Levels of IL-6 also correlate with shorter telomere length in patients with COPD, indicating a process of accelerated biological aging. This suggests that pulmonary hypertension secondary to COPD or chronic hypoxia may be due to inflammation-associated acceleration of normal pulmonary vascular cell sénescence.Conclusion. Inflammation in general, and IL-6 in particular, appear to be strongly involved in the pathophysiology of pulmonary vascular remodeling in patients with COPD

Le Syndrome d’Apnée Obstructive du Sommeil affecte 4 à 6 % de la population en France soit près de 3 millions de personnes. Toutefois, les techniques de diagnostic usuelles ne permettent pas de déterminer de façon précise les sites d’occlusion ni de décrire les interactions fluide-paroi qui jouent un rôle important dans les processus de fermeture des voies aériennes supérieures. Au cours de ce travail, un ensemble d’outil a été mis en œuvre pour explorer les mécanismes sous-jacents conduisant à une apnée obstructive. La détermination géométrique et la caractérisation mécanique des voies aériennes supérieures, d’une part, la mesure des écoulements dans ces dernières, d’autre part, ont été réalisées par imagerie par résonance magnétique de l’hydrogène, pour les tissus, de l’hélium-3 et du fluor-19 pour les gaz. Les données obtenues ont été exploitées tout d’abord dans un modèle numérique statique pour estimer les lois d’état locales et caractériser la compliance des voies aériennes supérieures, puis, dans un modèle monodimensionnel, prenant en compte l’interaction fluide-structure et la limitation de débit au cours de l’inspiration, pour localiser les sites potentiellement responsables d’un éventuel collapsus. Par ailleurs, les écoulements de gaz d’hélium-3 et d’hexafluorure de soufre ont été simulés afin de déterminer le potentiel de ces deux modalités d’imagerie de gaz pour l’étude des obstructions des voies aériennes. La faisabilité d’une imagerie statique et dynamique par résonance magnétique du fluor a été démontrée. Avec une densité du gaz traceur bien plus importante, cette dernière technique présente une plus grande sensibilité à l’obstruction. Cette thèse ouvre ainsi une nouvelle voie de diagnostic et de guide thérapeutique personnalisé pour ce syndrome. / Obstructive Sleep Apnea (OSA) is a common disorder occurring in almost 3 million French people. However, current diagnosis methods are not sufficient to precisely define obstructing sites and doesn't take into account the fluid structure coupling which plays an important role during upper airway closing. During this thesis, we developed a series of tools exploring upper airway closing process. On the one hand, a screening tool of the structure and the mechanical properties of the upper airway, and on the other hand, a screening tool exploring with dynamic images of inert gases flow into the upper airway, were obtained using conventional hydrogen MRI coupled to magnetic resonance elastography (MRE) and helium-3 or fluor-19 gases MRI, respectively. Geometric and biomechanical data obtained using MRI/MRE are injected into a numerical model given the compliance and the state law of upper airway. Contributions of anatomical restriction on airway collapse are also investigated using a multi-compartmental two-dimensional fluid structure interaction model during a breath inspiration to predicted airway mechanical changes and collapse pressures. Furthermore, helium 3 and sulfur hexafluoride flow was modeled at steady state using commercial finite volume software to evaluate potential feasibility to image upper airway collapsibility during OSA. First dynamic MR imaging using sulfur hexafluoride (SF6) was obtained showing the feasibility of this technique. Using SF6, 6 times denser than air, shows a higher sensibility to upper airway obstruction. This thesis opens a new imaging modality to probe and to diagnose upper airway obstruction.

Chan, Wai Kiu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 233-256). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract and appendix also in Chinese.

Chung Mei-lan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 118-124). / Abstracts in English and Chinese. / Abstract --- p.i / Declaration --- p.v / Acknowledgment --- p.vi / Abbreviations --- p.viii / List of Figures --- p.x / List of Tables & Graphs --- p.xi / Chapter 1. --- Background --- p.1 / Chapter Chapter 1: --- Age-Associated Changes in Nutritional Status in the Elderly --- p.1 / Chapter 1.1. --- Body Composition --- p.1 / Chapter 1.2. --- Nutritional Requirements --- p.2 / Chapter 1.2.1. --- Energy requirement in the elderly --- p.3 / Chapter 1.2.2. --- Protein requirement in the elderly --- p.3 / Chapter 1.2.3. --- Vitamin and minerals requirement in the elderly --- p.4 / Chapter 1.3. --- Food Intake --- p.4 / Chapter 1.3.1. --- Biobehavioral factors --- p.5 / Chapter 1.3.2. --- Social factors --- p.9 / Chapter 1.3.3. --- Psychological factors --- p.9 / Chapter 1.3.4. --- Physical factors --- p.10 / Chapter 1.3.5. --- Medical factors --- p.10 / Chapter 1.4. --- Age-Related Changes in Gastrointestinal Tract --- p.10 / Chapter Chapter 2: --- Energy Expenditure in the Elderly --- p.12 / Chapter 2.1. --- Total Daily Energy Expenditure (TEE) --- p.13 / Chapter 2.2. --- Basal Metabolic Rate (BMR) --- p.14 / Chapter 2.2.1. --- Mechanisms Leading to a Decrease in FFM Adjusted BMR --- p.15 / Chapter (i) --- Sex --- p.15 / Chapter (ii) --- Sympathetic Nervous System (SNS) Activity --- p.16 / Chapter (iii) --- Physical Activity --- p.17 / Chapter (iv) --- Body Weight --- p.17 / Chapter (v) --- Hormones --- p.18 / Chapter 2.3. --- Diet-Induced Thermogenesis (DIT) --- p.18 / Chapter 2.4. --- Energy Costs of Physical Activity --- p.20 / Chapter Chapter 3: --- Methods for the Measurements of Energy Expenditure --- p.22 / Chapter 3.1. --- Direct Calorimetry --- p.22 / Chapter 3.1.1. --- Principle of Direct Calorimetry --- p.22 / Chapter 3.1.2. --- Isothermal calorimetry --- p.23 / Chapter 3.1.3. --- Gradient-layer direct calorimetry --- p.23 / Chapter 3.1.4. --- Advantages and Disadvantages of Direct Calorimetry --- p.24 / Chapter 3.2. --- Indirect Calorimetry --- p.25 / Chapter 3.2.1. --- Principle of Indirect Calorimetry --- p.25 / Chapter 3.2.2. --- Whole body indirect calorimetry --- p.25 / Chapter 3.2.3. --- "Indirect calorimetry: ventilated hood system, a face mask, or mouthpiece" --- p.26 / Chapter 3.2.4. --- Advantages and Disadvantages of Indirect Calorimetry --- p.27 / Chapter 3.3. --- The Doubly-Labeled Water Method --- p.27 / Chapter 3.3.1. --- Principle --- p.27 / Chapter 3.3.2. --- Advantages and Disadvantages --- p.28 / Chapter 3.4. --- The Labeled Bicarbonate Method --- p.29 / Chapter 3.4.1. --- Principle of Isotope Dilution Method --- p.29 / Chapter 3.4.2. --- Principle of Traditional Labeled HC03 Method --- p.32 / Chapter 3.4.3. --- Labeled Bicarbonate-Urea Method --- p.34 / Chapter I. --- Calculations --- p.35 / Chapter A. --- Determination of energy equivalent of CO2 --- p.35 / Chapter B. --- Relationship between specific activity of urea and specific activity of CO2 --- p.35 / Chapter C. --- Fixation of infused label in the body --- p.36 / Chapter D. --- Calculation of CO2 production from the specific 3 activity of urinary urea --- p.6 / Chapter E. --- Two assumptions in labeled bicarbonate-urea method --- p.36 / Chapter 3.4.4. --- Advantages and Disadvantages of Labeled Bicarbonate-Urea Method --- p.37 / Chapter 3.5. --- Heart Rate Monitoring --- p.37 / Chapter 3.5.1. --- Principle --- p.37 / Chapter 3.5.2. --- Advantages and Disadvantages --- p.38 / Chapter 3.6. --- Activity Monitoring --- p.39 / Chapter 3.6.1. --- Principle --- p.39 / Chapter 3.6.2. --- Advantages and Disadvantages --- p.39 / Chapter 3.7. --- Activity Diaries --- p.40 / Chapter 3.7.1. --- Retrospective activity questionnaires --- p.40 / Chapter I. --- Principle --- p.40 / Chapter II. --- Advantages and Disadvantages --- p.40 / Chapter 3.7.2. --- Current diary method --- p.41 / Chapter I. --- Principle --- p.41 / Chapter II. --- Advantages and Disadvantages --- p.42 / Chapter 3.7.3. --- Time-and-motion study --- p.42 / Chapter I. --- Principle --- p.42 / Chapter II. --- Advantages and Disadvantages --- p.43 / Chapter Chapter 4: --- Nutritional Status and Energy Expenditure in Chronic Obstructive Pulmonary Disease (COPD) Patients --- p.44 / Chapter 4.1. --- Nutritional Status --- p.44 / Chapter 4.1.1. --- Body weight --- p.44 / Chapter 4.1.2. --- Fat-free mass (FFM) --- p.44 / Chapter 4.2. --- REE --- p.46 / Chapter 4.3. --- DIT --- p.47 / Chapter 4.4. --- TEE --- p.47 / Chapter 4.5. --- Nutrition Repletion by Caloric Supplement --- p.48 / Chapter 2. --- Objectives --- p.50 / Chapter 3. --- Subject and Method --- p.51 / Chapter 3.1. --- Part A: Subject and Methods I --- p.51 / Chapter 3.1.1. --- Subjects --- p.51 / Chapter 3.1.2. --- Methods --- p.51 / Chapter I. --- Anthropometric Assessment --- p.51 / Chapter II. --- Nutrient Intake --- p.52 / Chapter III. --- Clinical Assessment --- p.52 / Chapter IV. --- Energy Expenditure --- p.53 / Chapter V. --- Mini Nutritional Assessment Questionnaire --- p.53 / Chapter VI. --- Statistical Analysis --- p.54 / Chapter 3.2. --- Part B: Subject and Methods II --- p.55 / Chapter 3.2. --- Subjects --- p.55 / Chapter I. --- Patients --- p.55 / Chapter II. --- Control subjects --- p.55 / Chapter 3.2.2. --- Methods --- p.56 / Measurement of TEE by Labeled Bicarbonate-Urea Method --- p.56 / Chapter I. --- Study Protocol --- p.56 / Chapter Figure 6: --- Study protocol in Hospital --- p.57 / Chapter II. --- Clinical Protocol --- p.58 / Chapter A. --- Preparing the infusion --- p.58 / Chapter B. --- "Inserting the subcutaneous cannula, and starting the infusion" --- p.58 / Chapter C. --- Urine collection --- p.59 / Chapter D. --- Blood sample --- p.59 / Chapter III. --- Laboratory Procedures --- p.60 / Chapter A. --- Measuring the radioactivity of the infused bicarbonate solution --- p.60 / Chapter B. --- Measuring of specific activity of urea --- p.60 / Chapter (i) --- Titration of hyamine hydroxide solution --- p.60 / Chapter (ii) --- Urine radioactivity quantification --- p.61 / Chapter (1) --- Removal of dissolved CO2 from urine --- p.61 / Chapter (2) --- Determination of specific activity of C02 --- p.62 / Chapter (a) --- Principle --- p.62 / Chapter (b) --- Laboratory procedures for the determination of specific activity of urea --- p.62 / Chapter IV. --- Measurement in Hospital --- p.63 / Chapter A. --- Anthropometry --- p.63 / Chapter B. --- Indirect calorimetry --- p.63 / Chapter (i) --- Principle --- p.63 / Chapter (ii) --- Measurement of REE --- p.64 / Chapter (iii) --- Measurement of DIT --- p.65 / Chapter C. --- Food supply and dietary record during the study --- p.65 / Chapter D. --- Record of physical activity in rehabilitation program --- p.66 / Chapter E. --- Mini Nutritional Assessment Questionnaire --- p.67 / Chapter V. --- Statistical Analysis --- p.67 / Chapter 4. --- Results --- p.68 / Chapter 4.1. --- Results of Part A Study --- p.68 / Chapter 4.1.1. --- Anthropometry --- p.68 / Chapter 4.1.2. --- Nutrient Intake --- p.69 / Chapter 4.1.3. --- Caloric Balance --- p.71 / Chapter 4.1.4. --- Mini Nutritional Assessment Questionnaire --- p.72 / Chapter 4.2. --- Results of Part B Study --- p.73 / Chapter 4.2.1. --- Anthropometric Data --- p.73 / Chapter 4.2.2. --- REE --- p.74 / Chapter 4.2.3. --- DIT --- p.75 / Chapter 4.2.4. --- Nutrient Intake --- p.75 / Chapter 4.2.5. --- TEE --- p.76 / Chapter 4.2.6. --- Caloric Balance --- p.77 / Chapter 4.2.7. --- Mini Nutritional Assessment Questionnaire --- p.77 / Chapter 4.3. --- Table 1-1 --- p.78 / Chapter 4.4. --- Table 2-1 --- p.89 / Chapter 4.5. --- Graph1 --- p.100 / Chapter 5. --- Discussion --- p.103 / Chapter 5.1. --- Anthropometry in COPD patients --- p.103 / Chapter 5.2. --- Caloric and Nutrient intake in COPD patients --- p.105 / Chapter 5.3. --- Resting Energy Expenditure (REE) --- p.107 / Chapter 5.4. --- Diet-Induced Thermogenesis (DIT) --- p.108 / Chapter 5.5. --- Total Daily Energy Expenditure (TEE) --- p.108 / Chapter 5.6. --- Caloric Balance --- p.109 / Chapter 5.7. --- Limitation of this Study --- p.112 / Chapter 5.7.1. --- 24-hrs dietary recall --- p.112 / Chapter 5.7.2. --- Bicarbonate-urea method --- p.113 / Chapter 5.7.3. --- Anthropometry of community healthy elderly --- p.113 / Chapter 5.8. --- Recommendations --- p.114 / Chapter 5.8.1. --- Anthropometry monitoring in COPD patients --- p.114 / Chapter 5.8.2. --- Caloric supplements --- p.114 / Chapter 5.8.3. --- Physical activity in COPD patients --- p.115 / Chapter 6. --- Conclusions --- p.117 / Chapter 7. --- References --- p.118 / Chapter 8. --- Appendix I --- p.125 / Chapter A. --- Calculation of Total Energy Expenditure (TEE) --- p.125 / Chapter B. --- Sample of Calculation of Total Energy Expenditure (TEE) in Part B of the Study --- p.129 / Chapter 9. --- Appendix II - Equations --- p.133 / Chapter 10. --- Appendix III - Flow Calibration --- p.136