published_or_final_version / Social Work / Master / Master of Social Work

The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.

Chronic respiratory diseases (CRDs) include chronic diseases involving the airways and other structures of the lung. In the current circumstance of Vietnam, people are exposed to numerous risk factors of CRD, such as heavy smoking, high frequency of pulmonary tuberculosis, chronic helminthiasis, allergic factors, migration and urbanization (the last associated with traffic-related pollution). The phenotype diagnoses should take into account the risk factors of each individual besides the clinical features, while the differential diagnoses mostly depend on the available techniques in each healthcare center. Our aim was to improve the differential diagnoses of the 3 most frequent CRDs: chronic obstructive pulmonary disease (COPD), asthma and COPD – asthma overlap syndrome (ACOS), in Vietnam. In the first part, we evaluated the prevalence of the allergen sensitization among patients with CRD, in regard to the urban and rural area in the South of Vietnam. House dust mites and cockroach droppings were the most frequent sensitizer. Compared with participants born in the urban setting, those born in the rural environment were less frequently sensitized and this protective effect disappeared in the case of migration from rural to urban areas. In the second part, we evaluated skin prick test as a method to screen dust mite sensitization in CRD in southern Vietnam. The data suggested that, in the present circumstance, skin prick test can be used to screen mite sensitization. In the third part, we evaluated the risk of mite sensitization in the native and migrant population, in regard to several environmental factors. Consistently with the hygiene hypothesis, compared to urban, exposure to high endotoxin concentration in rural was a protective factor against allergic sensitization. We reported for the first time that this effect was reversible among the migrants from rural to urban setting in association with lower endotoxin exposure. In the fourth part, we have defined asthma, COPD and ACOS based on clinical symptoms, cumulative smoking and airway expiratory flow with reversibility, on one side, and the age-related of the different phenotypes, on the other side. We hypothesized that the cumulative exposure to noxious particles should increase the age-related prevalence of COPD, while due to the immunosenescence process, the prevalence of IgE-mediated asthma should decrease with age, and ACOS prevalence being not related to age due to the combined mechanisms.  In conclusion, we showed in the South of Vietnam that:1) mites and cockroach allergens were the most frequent sensitizer in chronic respiratory diseases;2) the skin prick test to mite has been validated to screen mite sensitization;3) associated with a reduced level of endotoxin level, migration from rural to the urban setting was a risk factor of mite sensitization in chronic respiratory diseases;4) based on the clinical symptoms, spirometric values, and cumulative smoking, the diagnosis of asthma, COPD and ACOS have been made and their prevalence were 25, 42 and 33%, respectively. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Les microARNs sont reconnus comme des régulateurs essentiels de l'expression des protéines. Des anomalies dans leur fonction sont associées au développement de nombreuses pathologies.tiel des microARNs en tant que biomarqueurs ou cibles thérapeutiques dans une grande variété de pathologies. Dans le cadre de cette thèse, nous avons étudié :1) L'association des microARNs urinaires avec l'évolution de la maladie rénale chronique (MRC) chez l'adulte. La prévalence de la MRC est actuellement estimée à 5-10% de la population et est en constante augmentation. La détection précoce et l'identification de patients ayant une MRC progressant rapidement vers l'insuffisance rénale sont la clé pour une meilleure prise en charge de ces patients. Actuellement les outils non-invasifs comme l'albuminurie ou l'estimation du débit de filtration glomérulaire manquent de précision. Dans notre travail, nous avons tenté d'identifier les modifications urinaires des microRNAs afin d'identifier de nouveaux biomarqueurs non-invasifs associés à la progression de la MRC. Nous avons analysé les modifications des microARNs urinaires par séquençage à haut débit dans des échantillons d'urine de 70 patients atteints de MRC et corrélé leurs profils d'expression à la progression de la maladie. Cela a amené à l'identification de 25 microARNs urinaires (pvalue ajustée <0.05) potentiellement associés à la progression de la MRC. Parmi ceux-là, quatre microARNs (hsa-miR-34c-5p, hsa-miR-410-3p, hsa-miR-301b-3p, and hsa-miR-145-5p) ont été sélectionnés pour être validés dans une cohorte indépendante de 52 patients atteints de MRC. L'augmentation de l'abondance urinaire de hsa-miR-145-5p a été confirmée comme étant associée à la progression de la MRC. Des analyses in vitro de l'effet de l'inhibition de hsa-miR-145-5p dans les cellules rénales ont mis en évidence que ce microARN semblait être impliqué dans le processus de nécrose. En conclusion, cette étude nous a permis d'identifier hsa-miR-145-5p comme Ainsi, de nombreuses études s'intéressent au potenmarqueur potentiel de la progression de la MRC. 2) La présence de microARNs urinaires associés à la néphropathie obstructive, une maladie fréquemment rencontrée chez les enfants qui peut conduire, dans les cas graves, à l'insuffisance rénale précoce. Dans cette étude, nous avons utilisé la biologie des systèmes et avons combiné des données microARN et ARNm de néphropathie obstructive humaine et animale pour obtenir des informations sur les mécanismes possibles impliqués dans cette maladie. En particulier, nous avons étudié simultanément le miRNome urinaire de nourrissons présentant une obstruction de la jonction pyélo-urétérale et le miRNome et le transcriptome tissulaire rénal chez la souris dans le modèle animal d'obstruction urétérale unilatéral (OUU) partiel et néonatal. Plusieurs centaines de microARNs et d'ARNms étant modifiés, la combinaison des microARNs des deux espèces avec les ARNms cibles associés a permis de sélectionner les 5 microARNs et 35 ARNms les plus fortement associés à la néphropathie obstructive. Une validation in vitro et in vivo a mis en avant que let-7a-5p et miR-29-3p ainsi que deux nouvelles cibles potentielles, l'E3 ubiquitin-protein ligase (DTX4) et neuron navigator 1 (NAV1) étaient dérégulées au cours de cette pathologie. Cette étude est la première à corréler le modèle animal d'OUU partiel et néonatal avec l'obstruction pyélo-urétérale chez l'Homme dans une analyse intégrée de biologie des systèmes. Nos résultats ont révélé let-7a et miR-29b en tant que molécules potentiellement impliquées dans le développement de la fibrose dans la néphropathie obstructive via le contrôle de DTX4 chez l'homme et la souris, ce qui n'aurait pas été identifiable autrement. / MicroRNAs are now recognized as key players in the regulation of proteins and any abnormality in their function is a cause for pathway instability, leading to pathological conditions. Numerous reports from a variety of pathologies provide new data about microRNAs function, their targets and their potential as biomarkers and possible ways to control microRNAs' expression for potential therapeutic purpose. A number of reports also connect microRNAs with pathological conditions in the kidney and point to the use of microRNAs as biomarkers for diagnosis and prognosis of kidney disease in blood, serum, tissue and urine samples. In this thesis, we researched:1) A possible role of the microRNAs in the progression of adult chronic kidney disease (CKD), a disease representing a global burden with the tendency to rise worldwide. Progression of CKD is still very hard to detect non-invasively with the currently used clinical tools (eGFR and albuminuria). In our work we studied alterations of the level of the microRNAs in human urine samples of patients with fast or slow progression of CKD, in order to identify new potential biomarkers for non-invasive progression of CKD. Using Next Generation Sequencing, we analyzed urinary microRNA modifications in urine samples of 70 patients with established CKD and correlated their expression profiles to disease progression. This lead to the identification of 25 urinary microRNAs significantly associated to CKD progression (adjusted pvalue<0.05). Among those, four microRNAs (hsa-miR-34c-5p, hsa-miR-410-3p, hsa-miR-301b-3p, and hsa-miR-145-5p) were selected for validation in an independent cohort of 52 patients with CKD. Increased urinary abundance of hsa-miR-145-5p was confirmed to be associated to progression of CKD. In vitro exploration of the effects of hsa-miR-145-5p inhibition in human kidney cells showed that the microRNA seemed to be involved in necrotic processes. In conclusion we have identified hsa-miR-145-5p as potential urinary microRNA marker of CKD progression. 2) The identification of microRNAs associated to obstructive nephropathy, a frequently encountered disease in children that can lead, in severe cases, to end stage renal disease (ESRD). In this study we used a comprehensive system biology analysis in which we combined micro- and mRNA data from human and animal obstructive nephropathy to obtain information on possible mechanisms involved in this disease. In particular, we have studied in parallel the urinary miRNome of infants with ureteropelvic junction (UPJ) obstruction and the kidney tissue miRNome and transcriptome of the corresponding neonatal partial unilateral ureteral obstruction (UUO) mouse model. Several hundreds of microRNAs and mRNAs displayed changed abundance during disease. Combination of microRNAs in both species and associated mRNAs let to the prioritization of 5 microRNAs and 35 mRNAs associated to disease. In vitro and in vivo validation identified consistent dysregulation of let-7a-5p and miR-29-3p and new potential targets, E3 ubiquitin-protein ligase (DTX4) and neuron navigator 1 (NAV1). Our study is the first to correlate a mouse model of neonatal partial UUO with human UPJ obstruction in a comprehensive systems biology analysis. Our data revealed let-7a and miR-29b as molecules potentially involved in the development of fibrosis in UPJ obstruction via the control of DTX4 in both man and mice that would not be identified otherwise.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

La Broncho-Pneumopathie chronique obstructive (BPCO) est un problème majeur en santé publique puisque ce sera la 3ème cause de mortalité en 2020. Il s'agit d'une maladie inflammatoire chronique du poumon se traduisant par une obstruction progressive des bronches, partiellement ou non réversible, incluant bronchite chronique, hypersécrétion de mucus et emphysème. L'atteinte ne se limite pas au poumon et affecte d'autres organes dont le tube digestif en favorisant la maladie de Crohn. Le premier facteur de risque impliqué dans le développement de cette maladie est l’exposition à la fumée de cigarette qui induit un stress oxydatif au sein du poumon responsable d'une inflammation chronique et du développement de la BPCO. L'interleukine-17 joue un rôle essentiel dans ce processus en contrôlant l'inflammation et l'altération de la fonction respiratoire. L'objectif de cette thèse est de comprendre les facteurs contrôlant cette réponse IL-17 afin de proposer ensuite de nouvelles voies thérapeutiques. Dans la première partie, nous nous sommes focalisés sur le stress oxydatif et à son impact sur les cellules de l’immunité innée. Ensuite, nous abordons le rôle d'un facteur immunorégulateur, l'IL-10, et à son interférence avec le microbiote digestif. Cela nous a amené à nous intéresser aux lésions digestives associées au tabagisme. Un modèle murin d’exposition chronique à la fumée de cigarette a été développé afin de reproduire la physiopathologie de la BPCO. Concernant l'impact du stress oxydatif, nous avons étudié le rôle des cellules iNKT (cellules ayant un puissant potentiel dans l’immunorégulation et dans l’inflammation) qui sont activées par ce type de stress. Les cellules iNKT sont rapidement recrutées et activées au sein du poumon suite à l’exposition à la fumée de cigarette. En utilisant des souris déficientes, nous avons montré l’importance de ces cellules dans la physiopathologie de la BPCO. Cette pathogénicité est dépendante de la production de l’interleukine-17 par ces cellules et est initiée par le stress oxydatif sur les cellules épithéliales pulmonaires et les cellules dendritiques qui activent les cellules iNKT.Dans la seconde partie du projet, l’IL-10 intervient notamment dans le contrôle de l'inflammation afin d’éviter le développement de réponses immunologiques exacerbées dans certains contextes. Dans les poumons exposés à la fumée de cigarette, la production d’IL-10 est augmentée et la déficience pour cette cytokine entraîne une augmentation de la réponse Th17 et du déclin de la fonction pulmonaire. Une dysbiose (altération du microbiote) est observée avec la fumée de cigarette et la déficience à l'IL-10. De plus, une déplétion des bactéries Gram+ par antibiothérapie permet de limiter le développement de la réponse IL-17 et de l'atteinte pulmonaire soulignant l'importance du microbiote. En conclusion, nous avons identifié le stress oxydatif et l'IL-10 comme facteurs intervenant dans la réponse IL-17 associé à la BPCO. Ce travail souligne également le rôle du microbiome comme un organe à part entière et la modulation de ce dernier pourrait aboutir à l'identification de nouvelles voies thérapeutiques. / Chronic Obstructive Pulmonary Disease (COPD) is a major health problem which is going to become the third leading cause of death worldwide by 2020. COPD is characterized by a chronic inflammation of the airways causing progressive bronchial obstruction, with no completely reversible airflow limitation, including chronic bronchitis, mucus hypersecretion and emphysema. The pathology is not limited to the airways and can affect others organs including the gastro-intestinal tract promoting Crohn disease. Cigarette smoke exposure is the most important risk factor for developing COPD. Exposure to cigarette smoke induces a strong burden of reactives oxygen species and this oxidative stress is responsible for a chronic inflammation and the development of COPD. Interleukin (IL)-17 plays a critical role in controlling process of inflammation and lung function decline.The aim of this thesis is the understanding which factors are controlling the IL-17 response in order to propose new therapeutic approaches.In the first part, we focused on oxidative stress and its impact on innate immune cells. Then we addressed the role of an immunoregulatory factor, the interleukin (IL)-10, and its interference with intestinal microbiota. This part lead us to study intestinal damages linked to cigarette smoking.To mimic the physiopathology of COPD, we set up a mouse model of chronic exposure to cigarette smoke. Concerning the impact of oxidative stress, we investigated the role of iNKT cells (cells with a crucial potent role in immunoregulation and inflammation) activated by this type of stress. iNKT cells rapidly accumulate and be activated within the lungs of cigarette smoke exposed mice. Using deficient mice, we demonstrated that these cells strongly contribute to the COPD pathogenesis. This pathogenicity is iNKT cells-produced IL-17 dependant and initiated by the effect of oxidative stress on airway epithelial cells and dendritic cells activating iNKT.In the second part of the work, IL-10 interferes notably in the inflammation control in order to avoid exacerbated immunological responses development in some contexts. In cigarette smoke exposed lungs, IL-10 production is up-regulated and the deficiency for this cytokine leads to an increased Th17 response and to lung function decline. An altered microbiota (named dysbiosis) is observed with cigarette smoke exposure and IL-10 deficiency. Moreover, Gram+ bacteria depletion using antibiotics is able to limit the IL-17 response development and the lung function decline highlighting the crucial role for microbiota.To conclude, we identified two factors, oxidative stress and IL-10, implicated in IL-17 response linked to COPD. This work also underlines the role of microbioma as a whole organ and the modulation of this microbioma could result in new therapeutic ways identification in COPD.

Hospital readmission is prevalent among people with chronic obstructive pulmonary disease (COPD), particularly among older people in Hong Kong. Evidence shows that hospital readmissions exert a considerable impact on patients. Studies in this area primarily identify various associative factors based on the perspectives of health professionals. However, these factors are inadequate in illustrating the needs of older people and in illuminating the phenomenon of hospital readmissions. A thorough understanding of the issue can be achieved if the related experiences are interpreted from the perspective of the patients and in terms of their context. Understanding of their experiences has paramount significance in uncovering the unmet needs of patients and in informing the provision of healthcare services. Yet, there is a dearth of studies unfolding the experiences of Chinese older people. / This study aimed to explore and describe the lived experience of hospital readmissions of Chinese older people with COPD and to identify Chinese socio-cultural influences on the experience. Understanding was acquired through descriptive phenomenology. Twenty-two Chinese older people aged 62 to 89 were recruited by purposive sampling. They had been readmitted 4 to 14 times in the previous year. The older people were interviewed once during their hospitalization, and their readmission experiences were elicited from these unstructured interviews. Narrative descriptions were analyzed using the phenomenological method described by Giorgi (1985). / The general structure of the lived experience of hospital readmissions of Chinese older people with COPD reveals that older people refrain from unnecessary readmissions because they regard hospital care as the last resort in relieving breathlessness. When their breathlessness becomes intolerable, they perceive the urgency of surviving the distress. Craving for survival, they seek hospital readmission, which provides them immediate relief from the imminent threat. After being readmitted to a hospital, they feel powerless when their need for hospital care is disregarded by their doctors. Considering themselves as demanding to their families in daily lives, older people remain conscious of relieving their burden during their periods of hospital readmission because they regard this as the only opportunity to relieve their burden. Older people come to realize hospital readmissions are unavoidable after they put every effort to refrain from it but hospital care remains necessary. They further rationalize hospital readmissions as inevitable and resign themselves to it because of their perception of aging, doctors’ accounts of COPD, experience with and knowledge of the disease, and belief in fate. This acceptance of the inevitability of hospital readmissions precipitates an attitudinal shift toward the belief of living for the moment. Their past experiences inspire them to be satisfied with the current state of living and engage the present. This positive outlook enables them to embrace the experiences of hospital readmissions into their lives. Six invariant constituents emerged from the lived experience. The constituent “refraining from unnecessary readmissions” describes how older people manage their diseases in relation to hospital readmissions. “Craving for survival” explains why they seek hospital readmissions. “Feeling being disregarded and powerless” and “being conscious of relieving burden to families” characterize their experience of hospital readmissions. “Resigning to hospital readmissions” illustrates how they understand the recurrence of this phenomenon and “living for the moment” illuminates how they live with their experiences. / A deep understanding of hospital readmissions is embodied in the experiences of older people. The findings emphasize that hospital readmissions among Chinese older people are complex experiences shaped by their sociocultural context. The meanings of hospital readmissions to older people are influenced by their assumption of a submissive patient role, collectivism, external attribution style, and past life experiences. Although older people appear to accept and cope well with hospital readmissions, this study uncovers their needs as they move to and fro the hospital and home. The findings of this study offer implications in promoting the wellness of Chinese older people as they go through this revolving door. / 再次住院在患有慢性阻塞性肺病人士中相當普遍，尤其是在中國老年患者。研究證據顯示再次住院對病人有很大的影響。現有的研究偏重於從醫務人員角度尋找不同的關聯因素，但該些因素並不足以反映老年人的需要以及解釋再次住院的現象。只有透過病人的觀點以及結合他們的背景來闡釋這些相關經驗，才能作出深入了解。了解病人的再次住院經驗有助於找出病人的需要以及指引醫療服務的提供。然而，有關中國老年人再次住院經驗的探討相當缺乏。 / 是次研究目的是探討和描述患有慢性阻塞性肺病的中國老年人再次住院的體驗，以及認識中國社會文化對再次住院經驗的影響。研究採用描述現象學方法。研究以立意抽樣方式選取了22名62至89歲的中國老年人。他們在去年入院次數為4至14次。這些老年人在住院期間均接受一次非結構式訪談以了解他們的再次住院經驗。這些敘述性描寫再按 Giorgi (1985) 的現象學方法作出分析。 / 患有慢性阻塞性肺病中國老年人再次住院的體驗的通用結構顯示他們避免不必要的再次住院，因為他們將住院護理視為紓緩呼吸困難的最後方法。當他們的呼吸困難惡化至無法忍受，他們會感受到從危病中活下來的迫切性。因著渴望生存的意識，他們尋求再次住院以即時消除緊迫的生命威脅。再次入院後，對於醫生漠視其住院護理的需要，他們感到無力。由於考慮到他們在日常生活中對家人的需求頗多，老年人以再次住院其間來減輕家庭負擔，因他們視這其間為唯一能減輕家庭負擔的機會。儘管老年人盡能力以避免再次入院，但他們依然需要住院護理，老年人逐漸意識到再次住院為無可避免。由於老年人對於老化的感知、醫生對慢性阻塞性肺病的解明、患病經驗和對疾病的相關知識以及相信命運的看法，他們更將再次住院合理化為無可避免並順從。接受再次住院為無可避免促成他們的態度轉變為活在當下。過去的經驗令他們對目前的生活感到滿意並希望活在當下。這個正面想法令他們將再次住院接納為生活的一部份。六個不變組成要素呈現於老年人的再次住院體驗當中。組成要素「避免不必要的再次住院」描述老年人如何管理慢性阻塞性肺病以避免再次住院。「渴望生存」解釋了他們尋求再次住院的原因。「感到被忽略和無力」以及「減輕家庭負擔的意識」敘述了他們再次住院的經驗。「順從再次住院」說明了他們對再次住院現象發生的理解，而「活在當下」說明了他們如何接納再次住院經驗。 / 對於再次住院的深入了解具體表現於老年人的經驗當中。是次研究結果強調，老年人再次住院是由他們的社會文化背景塑造而成的複雜經驗。對於老年人而言，再次住院的意義受到他們對順從性病人角色的假設、集體主義觀念、外部歸因以及過往的生活經驗所影響。雖然老年人似乎接受並適應再次住院，是次研究發現了他們在這現象中的需要。研究結果對於促進再次住院的中國老年人的健康帶來新的啟示。 / Tang, Wing Ki. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 342-393). / Abstracts also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.