Chronic Hepatitis B (CHB) related cirrhosis and hepatocellular carcinoma (HCC) account for more than 750,000 deaths per year. Current therapies for CHB are limited in achieving HBsAg decline/loss and thus there remains a pressing need for curative treatment strategies. Although, Pegylated Interferon-α (Peg-IFNα) may be used, the majority of patients progress to nucleos(t)ide analogue (NUC) therapy due to treatment failure. Peg-IFNα and NUCs used in isolation act differentially on the immune response; Peg-IFNα induces NK cell activation and NUC therapy may partially restore T cell function. NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined the NK cell pool in HBeAg-positive CHB patients treated with Peg-IFNα and whether changes in the NK cell repertoire are induced when patients are 'primed' with Peg-IFNα and importantly, whether these changes are sustained or further modulated long-term after switching to sequential NUC therapy. The cumulative expansion of CD56bright NK cells driven by 48-weeks of Peg-IFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Peg- IFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors during sequential NUCs. The expansion in proliferating, functional NK cells and HBsAg reduction was greater and more pronounced following sequential NUCs than in patients treated with de novo NUCs. This highlights the potential benefit of Peg-IFNα- priming, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses. Sustained boosting of NK cells on sequential NUCs following Peg-IFNα-priming has not previously been described raising the potential of 'long-lived' NK cell populations in keeping with their emerging adaptive features. These findings provide a mechanistic and immunological rationale to explore combination/sequential treatment strategies for CHB, including on-treatment immune responses in the liver, whilst awaiting the emergence of new therapies in the field.

Traumatic brain injury (TBI) is a serious public health concern. Although moderate and severe forms of TBI receive considerable attention, mild TBI accounts for the majority of all injuries. The first two aims of this work used a rodent model of mild blast to simulate primary injury (damage from the blast wave only). The first aim evaluated potential changes in interneurons containing the calcium-binding proteins calretinin or parvalbumin. In addition, morphological changes in astrocytes and microglia were assessed. Brains were analyzed 48 hours and one month following exposure to single or repeated blasts, with a focus on the hippocampus due to its integral role in learning and memory. Results showed significant region-specific alterations in microglia morphology 48 hours following blast. The absence of structural alterations in microglia one month following blast indicated that the regional hippocampal vulnerability may be transient. The second aim compared glial morphologies in the retina and brain (the lateral geniculate nucleus, superior colliculus, and visual cortex) 48 hours or one month following multiple blasts. Fiber degeneration has received considerable attention, however, less is known about the status of glia throughout the visual pathway following mild blasts. Although no structural alterations were detected, it is possible that alterations in glia occurred at a more acute time scale as changes in glia can be rapid and reversible. The final aim of this work focused on the immunocytochemical characterization of tau pathology in the visual cortices of human postmortem brains with advanced chronic traumatic encephalopathy (CTE). CTE is a devastating tauopathy associated with mild, repetitive TBIs. Although visual deficits are reported in CTE, the primary visual cortex is often spared. The main hypothesis under investigation was whether visual association areas would have tau pathology, despite sparing of primary visual cortex. In addition, a sub-class of interneurons containing parvalbumin was used to evaluate a potential cell-specific vulnerability. Results showed increased tau pathology in visual association areas in advanced CTE, that was largely absent from the primary visual cortex. There was no effect on parvalbumin positive interneurons. The results of this work provides valuable insight regarding potential cell-specific resistance to CTE pathology. / 2018-11-03T00:00:00Z

Postmortem brains from young athletes with a history of repetitive concussive head injury and military service personnel with history of blast neurotrauma revealed evidence of parenchymal contusion, myelinated axonopathy, microvasculopathy, neuroinflammation, neurodegeneration, and phosphorylated tauopathy consistent with chronic traumatic encephalopathy (CTE) (L. E. Goldstein et al., 2012). The mechanisms by which head trauma induces acute concussion and chronic sequelae are unknown. To elucidate the mechanistic connection between traumatic brain injury (TBI), acute concussion and chronic sequelae, including CTE, require the use of animal models. This doctoral dissertation investigated the hypothesis that closed-head impact injury in mice triggers acute neurological signs associated with sport-related concussion as well as brain pathologies and functional sequelae associated with CTE. To test this hypothesis, we developed a mouse model of impact neurotrauma that utilizes a momentum transfer device to induce non-skull deforming head acceleration, triggering transient neurological signs consistent with acute concussion and traumatic brain injury (TBI) in unanesthetized C57BL/6 mice. The Boston University Concussion Scale (BUCS) was developed to assess neurological signs that are consistent with acute concussion in humans. Mice exhibited contralateral circling and limb weakness, locomotor abnormalities, and impaired gait and balance that recapitulate acute concussion in humans. Concussed mice recovered neurological function within three hours, but demonstrated persistent myelinated axonopathy, microvasculopathy, neuroinflammation, and phosphorylated tauopathy consistent with early CTE. Concussive impact injury also induced blood-brain barrier disruption, neuroinflammation (including infiltration peripheral monocytes and activation microglia), impaired hippocampal axonal conduction, and defective long-term potentiation (LTP) of synaptic transmission in medial prefrontal cortex. Kinematic analysis during impact injury revealed head acceleration of sufficient intensity to induce acute concussion, traumatic brain injury (TBI), early CTE-linked pathology, and related chronic sequelae. Surprisingly, the presence or degree of concussion measured by BUCS did not correlate with brain injury. Moreover, concussion was observed following impact injury but not blast exposure under conditions that induce comparable head kinematics. Empirical pressure measurements and dynamic modeling revealed greater pressure on the head and compression wave loading in the brain during impact compared to blast neurotrauma. These findings suggest acute concussion is triggered by focal loading of energy that transit the brain before onset of macroscopic head motion. By contrast, the forces associated with rapid head motion is sufficient to induce CTE-linked pathology. Our results indicate that while acute concussion and chronic sequelae may be triggered by the same insult, the pathophysiological responses underpinning these effects are engaged through distinct mechanisms and time domains. Our results indicate that concussion is neither necessary nor sufficient to induce acute brain injury or chronic sequelae, including CTE. / 2018-02-17T00:00:00Z

Introduction: Derangement of systemic and mucosal immunity, which are the integral components of the immune system, increases the risk of septic complications in patients postoperatively. The aims of this study were to investigate the integrity of systemic immunity as well as the mucosal immune system in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and obstructive jaundice (OJ).Method: Healthy controls, as well as four groups of patients were studied. These included; jaundiced patients with PC, jaundiced patients secondary to benign disease (choledocholithiasis), non-jaundiced patients with PC and non-jaundiced patients with CP. The study evaluated the nutritional status including anthropometric measurements and the serum proteins: retinal binding protein (RBP), transferrin (TRF) and prealbumin (PALB). This study also evaluated systemic immunity in terms of total lymphocyte count, lymphocyte subsets (CD4+, CD8+, CD25+and CD56+), tumour necrosis factor alpha (TNF- alpha), interleukin-1alpha (IL-1 alpha) and complement components; and mucosal immunity in terms of CD3+, CD4+, CD8+, CD20+, CD57+, CD68+ and mast cells. Results: 78 patients were recruited (including 39 males) as follows: normal controls (n=17), benign OJ (n=9), patients with PC with jaundice (n=23), non-jaundiced patients with PC (n=20) and CP (n=9). Circulating CD25+ and CD4+ were significantly lower in the PC group whereas CD8+ showed increased levels in the same patients with a significant decrease in OJ patients when compared with controls. Circulating CD56+ showed no statistically significant difference between all four groups. In addition, IL-1 and TNF-alpha showed no statistically significant difference in all groups when compared with the control group. Also, C3 and CH50 showed significantly raised levels in PC with jaundice when compared with the control group. On the other hand mucosal lymphocyte subsets showed no statistically significant difference among all groups in comparison with the control group. As for prealbumin and transferrin, both showed significantly low levels in OJ, PC with jaundice and with PC when compared to healthy controls. Survival analysis for both PC groups was carried out and showed no difference in terms of age, however PC patients who survived over 13 months showed increased levels of prealbumin as well as low levels of CH50.Conclusion: Patients with PC both with and without jaundice showed some signs of altered and dysfunctional systemic immunity as well as a reduction in serum proteins. These findings may have implications on the disease progression and postoperative complications. This may warrant therapeutic interventions to restore nutrition and improve immunity before major surgical intervention is planned which could result in improving prognosis.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-20Bitstream added on 2014-06-13T19:07:29Z : No. of bitstreams: 1 suman_p_me_botfm.pdf: 1196436 bytes, checksum: 8dcde5816493bed62c06995c961056df (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A relação entre a doença renal crônica (DRC) e a deficiência auditiva (DA) vem sendo estabelecida através de estudos na área. Apesar de a hipertensão arterial e diabetes mellitus estarem frequentemente relacionados às duas patologias, poucos estudos levam em consideração seus efeitos sobre os achados audiológicos dessa população. O efeito do tipo de tratamento para DRC sobre a audição, bem como a localização da perda auditiva ainda são inconclusivos. O objetivo deste trabalho foi de verificar o efeito da DRC e dos tratamentos conservador, diálise peritoneal e hemodiálise, sobre a cóclea e nervo auditivo, levando-se em consideração o efeito das variáveis hipertensão arterial e diabetes mellitus. Sujeitos com idade acima de 60 anos, deficiência auditiva congênita, síndromes genéticas e/ou submetidos a transplante renal foram excluídos. Foram realizados Audiometria Tonal Limiar (ATL), Timpanometria, Emissões Otoacústicas Evocadas Transientes (EOAET) e Potencial Evocado Auditivo de Tronco Encefálico (PEATE) em 101 sujeitos com DRC, subdivididos em 03 grupos, de acordo com o tipo de tratamento (A1: hemodiálise/ n=35; A2: diálise peritoneal/ n=15 e A3: conservador/ n=51) e um grupo controle foi formado por 27 sujeitos saudáveis (B). Entre os portadores de DRC, a hipertensão esteve presente em 86,1% dos sujeitos e o diabetes em 29,7%. A idade média dos doentes foi 46,7 (±12,3) anos enquanto que a do controle foi 36,6 (±12). Apresentaram DA uni ou bilateral 32,7% dos sujeitos do grupo A e não houve diferença estatisticamente significante da sua frequência entre os subgrupos A. Quanto ao tipo da perda, 92% das orelhas (n=45) foi neurossensorial e 8% mista (n=4). Quanto ao grau, 67% das orelhas (n=33) apresentaram perda leve, 20% (n=10) moderada, 5% (n=2) grave e 8% (n=4) profunda e não houve diferença significante do grau entre os subgrupos A. / The relation between chronic renal disease (CRD) and hearing loss (HL) has been determined by studies in the field. Despite arterial hypertension (AH) and diabetes melitius (DM) are frequently associated to both conditions, few studies considered their effects on the audiological findings in this population. The effects of the type of treatment for CRD on the hearing as well as on the site of the hearing loss are still inconclusive. The aim of this study was to verify the effect of the CRD, of different treatments: conservative, peritoneal dialysis and hemodialysis on the cochlea and on the auditory nerve, considering the effects of AH and DM. Subjects over 60 years, with born hearing deficiency, genetic syndromes and/or submitted to renal transplant were excluded. The 101 subjects with CRD were tested with Pure Tone Audiometry (PTA), Tympanometry, Transitory Evoked Otoacoustic Emissions (TEOE) and Auditory Brainstem Response (ABR). Subjects were divided in 3 groups according to the type of treatment (A1: hemodialysis/ N=35; A2: peritoneal dialysis/ N=15; A3: conservative/ N=51). The control group constituted of 27 health individuals (B). Among the individuals with CRD, 86.1% presented AH and 29.7% presented DM. The mean age was 46.7 y (± 12.3) in the group with CRD and 36.6 y (± 12) in the control group. In group A 32.7% of the subjects presented uni- or bilateral HL with no statistical difference between sub-groups. In what refers to the type of hearing loss, in 92% of the ears (N=45) it was neuro-sensorial and in 8% (N=4) it was mixed. The degree was mild in 63% (N=33) of the ears, moderate in 20% (N=10), severe in 5% (N=2) and profound in 8% (N=4), without significant differences between subgroups. When compared to group B, the group A presented significantly lower hearing thresholds on the PTA, smaller amplitude on the TEOE and more alterations on the ABR (10.4%/ N = 21 ears).

This study aims to contextualise my own photographic practice in relation to the interaction between mundane and sacred landscapes and the role that the transformative alchemy of light has on our perception of the ordinary. Reference will be made to the development of the genre of landscape photography, with particular reference to the selective aesthetic of pristine Wilderness, as embodied in the work of Ansel Adams, through the ‘man-altered’ landscapes of the New Topographics and Mark Klett’s rephotographic project, to discuss an aesthetic of the everyday. Reference will also be made to the benefits to health and wellbeing that can be achieved as a result of engaging in a state of mindfulness (Crane), also known as optimal experience or flow (Csikszentmihalyi) through photographic practice. Rather than narrowing the focus of the study by excluding relevant information to make the research less complex, the thesis comprises information from a diverse range of disciplines encompassing both the more obviously creative subjects of photography, aesthetics and poetry and areas such as health care. Given the parameters of the PhD process in relation to the breadth of the research undertaken, the specific study of each diverse element is, of necessity, not as detailed as it may have been had a single, more specifically defined, area of research been the entire focus of the research. The inclusive nature of the research presented in this thesis offers unique insights by providing direct comparisons and establishing new relationships between the theoretical and methodological approaches of a range of differing disciplines. While a written thesis forms part of the dissemination of the research findings the images that have emerged as a result of engagement with the study will be exhibited as an integral element of the outcome. The images that have been created as a result of the research process will take their place as objects within the world, offering viewers potential new ways of perceiving and experiencing what Rancière refers to as the ‘splendour of the insignificant’ within the landscape of their own everyday lives.

Orientador: Paula Rahal / Banca: João Renato Rebello Pinho / Banca: Maurício Lacerda Nogueira / Resumo: O HCV é uma das maiores causas de doença do fígado, sendo estimado que mais de 2% da população mundial está infectada. Este vírus possui um genoma de RNA (+) fita simples, que devido à falta de atividade corretiva da polimerase viral apresenta variabilidade genética em vários níveis: genótipos, subtipos e quasispecies. O genótipo 1 é o mais prevalente no Brasil e no mundo, sendo preditivo de uma baixa resposta à terapia antiviral, que atualmente é baseada na administração de PEG-IFN e ribavirina. A variabilidade genética da região viral NS5A tem sido relacionada à sensibilidade ou resistência ao IFN. Este estudo teve como objetivo investigar se a possível relação entre a composição de quasispecies da NS5A e a resposta ao tratamento. Foram selecionados 12 pacientes, sendo 4 respondedores (R), 4 não respondedores (NR) e 4 respondedores ao final do tratamento (RFT). As amostras pré-tratamento destes pacientes foram amplificadas, clonadas e seqüenciadas, resultando em 165 seqüências da NS5A completa. Estas seqüências foram alinhadas, editadas e a construção da topologia da árvore filogenética foi realizada. A NS5A e suas regiões específicas CRS, PKR-binding, ISDR, NLS e V3 foram analisadas quanto às substituições e o grau de variabilidade genético. O grupo de pacientes RFT apresentou uma maior taxa de substituições sinônimas em relação aos demais grupos. Uma maior quantidade de mutações foi observada na região downstream à ISDR, principalmente na região V3. Nenhum sítio específico de mutação foi relacionado a um tipo particular de resposta, e não houve agrupamento filogenético das quasispecies de acordo com o tipo de resposta. Estes resultados sugerem que o número de mutações não é suficiente para predizer a sensibilidade ou resistência à terapia baseada em IFN, sendo necessário avaliar se estas mutações conservaram ou não as propriedades químicas dos aminoácidos. / Abstract: Hepatitis C virus (HCV) is major causes of liver desease and about 2% of world s population are infected. This virus is a single strain RNA genome of approximately 9.6 kb. Genetics variability of HCV exists at several different levels: genotypes, subtypes and quasispecies. The high mutation rates are related to the low fidelity of viral RNA polymerase. Genotype 1 HCV is the most prevalent in Brazil, as well as worldwide. Genotypes 1a and 1b are predictive of lower sustained virological response in peginterferon (PEG-IFN) plus ribavirin combination therapy. Genetic variability of viral NS5A has been related to IFN sensibility or resistance. To evaluate whether HCV NS5A quasispecies composition are related to responsiveness to combined PEG-IFN and ribavirin therapy, this study analyzed before treatment sample of 12 treated patients (4 sustained responders - SR, 4 non responders - NR and 4 end of treatment responder - ETR). Samples were amplified, cloned and sequenced, resulting in 165 sequences of complete NS5A. Sequences were aligned, edited and phylogenetical tree was constructed. Mutations and mean of genetic distance were analyzed to NS5A and specific regions CRS, PKR-binding, ISDR, NLS and V3. The number of synonymous substitutions per synonymous sites was higher in ETR patients than in other patient groups. Mutations were more common downstream ISDR, mainly concentrated in V3 domain. No single amino acid position or motif was associated with different responses to therapy in any NS5A regions analyzed and phylogenetic analysis did not show clustering of nucleotide sequences of viral isolates from SR, NR or ETR. These results suggest that number of mutations is not sufficient to predict sensibility or resistance to IFN based therapy. Other studies are necessary to evaluate whether chemical characteristics of amino acids were altered for the mutations. / Mestre

Considerando a espiritualidade como parte do conceito de saúde do indivíduo e suas repercussões no viver a doença crônica, realizou-se o presente estudo. Trata-se de um estudo exploratório, com metodologia quanti-qualitativa que teve como objetivo principal identificar e compreender o papel da espiritualidade no manejo da doença crônica do idoso. Procurou-se ainda conhecer o perfil dos idosos participantes do estudo, as mudanças de vida ocasionadas pelo diagnóstico da doença crônica e a compreensão de como a religião/espiritualidade/fé interfere neste processo. O método da análise de conteúdo de Bardin foi escolhido para interpretação dos discursos. O estudo foi realizado com 20 idosos portadores de doença crônica atendidos no Instituto Paulista de Geriatria e Gerontologia José Ermírio de Moraes (IPGG), instituição que tem como missão promover o envelhecimento saudável e a integração social do idoso. A coleta de dados foi realizada em outubro de 2010, através de entrevistas semiestruturadas. Os idosos possuíam entre 60 e 81 anos, sendo 65% mulheres e 35% homens, 65% casados, 20% viúvos e 15% divorciados. Quanto à ocupação, 80% são aposentados, 10% do lar/donas de casa, 10% estão ativos no mercado de trabalho. Com relação às condições de moradia, 85% residem em casa própria, 10% em casas de familiares e 5% em casa alugada, 50% residem com cônjuge e filhos ou netos, 35% apenas com cônjuge, 10% moram sozinhos e 5% apenas com filho. Quando questionados quanto às crenças religiosas, todos os participantes referiram pertencer a uma doutrina religiosa e dentre as religiões 75% declarou-se católico, 20% evangélico e 5% espírita. A doença crônica mais prevalente foi a Hipertensão Arterial Sistêmica (HAS), referida por 45% dos participantes, seguida do diabetes mellitus, presente em 35% dos idosos. A análise dos discursos resultou nos seguintes temas centrais: impacto multidimensional da doença crônica, enfrentamento e expectativas dos idosos. Na análise do impacto multidimensional da doença crônica, identificaram-se as seguintes unidades temáticas: impacto no estilo de vida, impacto emocional e impacto socioeconômico. Com relação ao enfrentamento da doença crônica, foram analisados o enfrentamento individual, o suporte social e a espiritualidade/religiosidade/fé. Quanto às expectativas, as unidades temáticas identificadas foram expectativas quanto à saúde e quanto ao sentido da vida. Os resultados evidenciaram as mudanças trazidas pelo diagnóstico da doença crônica e suas implicações na adaptação ao novo modo de vida. O manejo destas alterações é complexo e diversos fatores influenciam positivamente e negativamente no modo de lidar com a nova condição. Os resultados mostraram que a espiritualidade/religiosidade/fé interfere de maneira positiva no enfrentamento dos obstáculos e dificuldades da vida, fortalece a resiliência do paciente, melhorando assim, sua qualidade de vida. Para que o manejo da doença crônica seja bem sucedido, o profissional de saúde atuante na assistência ao idoso portador de doença crônica deve ter a sensibilidade de compreender o idoso dentro de seu contexto cultural e fortalecer o entendimento e responsabilização do paciente quanto a sua condição crônica. / This study was carried out considering spirituality as part of the concept of health and its impacts on living with a chronic disease. It is an exploratory study with quanti-qualitative methodology that aimed to identify and understand the role of spirituality in the management of chronic disease of the elderly, by identifying the profile of individual participating in the study, the life changes caused by diagnosis of chronic disease and how religion/spirituality/faith interferes in this process. The technique of contents analysis of Bardin was chosen for the interpretation of discourse. The study was conducted with 20 elderly patients with chronic disease treated at the Instituto Paulista de Geriatria e Gerontologia José Ermírio de Moraes (IPGG), an institution whose mission is to promote healthy aging and social integration of the elderly. Data collection was conduted in October 2010, through semi-structured interviews. The elderly had between 60 and 81 years, being 65% women and 35% men, 65% married, 20% widowed and 15% divorced. As to occupation, 80% are retired, 10% housewives, 10% are active in the labor market. About the conditions of living, 85% live in their own home, 10% in relatives house and 5% in rented accommodation, 50% live with spouse and children or grandchildren, 35% with spouse, 10% living alone and 5% living with children. When asked about their religious beliefs, all participants reported belonging to a religious doctrine, 75% declared themselves Catholic, 20% Protestant and 5% Spiritualist. The most prevalent chronic disease was High Blood Pressure, reported by 45% of the respondents, followed by Diabetes, present in 35% of the elderly. The discourse analysis resulted in the following themes: the multidimensional impact of chronic disease, coping and expectations of the elderly. In the analysis of the multidimensional impact of chronic disease, we identified the following thematic units: impact on lifestyle, emotional impact and economic impact. When regarding to coping with chronic illness, we analyzed the individual coping, social support and spirituality/ religion/ faith. As for expectations, thematic units identified were expectations about health and expectations about the meaning of life. The results demonstrate the changes brought by the diagnosis of chronic disease and its implications for adaptation to the new way of life. Management of these changes is complex and many factors influence both positively and negatively in dealing with the new condition. The results show that spirituality/religion/faith interferes positively in addressing the obstacles and difficulties of life, strengthen the resilience of the patient, thus improving their quality of life. For chronic disease management to be successful, health professionals active in assistance of the elderly with chronic illness should have the sensitivity to understand the elderly within their cultural context and strengthen their understanding and their accountability about the chronic condition.

Magister Chirurgiae Dentium (MChD) / Chlorhexidine has been established as the gold standard against which new chemical plaque control agents are tested (Jones, 1997). The addition of alcohol in a chlorhexidine mouthwash had been widely used, however the comparative efficacy of alcohol free chlorhexidine mouthwash had not fully been explored in this study, two chlorhexidine mouthwash preparations were tested to evaluate their comparative efficacy in the treatment of periodontal disease. Aims: To assess the efficacy of alcohol-free chlorhexidine mouth wash in comparison to alcohol containing chlorhexidine mouth wash. Objectives: To determine pre- and post- operative clinical parameters and microbial load in the management of patients with chronic periodontitis. Methodology: A double blinded randomised control trial was conducted. Patients diagnosed with active chronic periodontitis were included in the study and randomised to either a test (chlorhexidine without alcohol) or control group (chlorhexidine with alcohol). A total of 50 patients were selected for the study. Results: The Wilcoxon Signed Rank test was used to test the difference between the pre-post pair per clinical indicator and Bana-Zyme. The differences between before and after treatment per indicator were significant at P<0.001 for respectively Paroex and Peridex. These values demonstrated the difference between the clinical parameters taken before the treatment and six weeks post treatment. Conclusion: Both mouth wash solutions with and without alcohol had proven to reduce the microbial load as shown by the BANA-Zyme test, with the alcohol containing solution having been more effective.

Among those subjects admitted with AECOPD and concomitant pneumonia, a total of 118 patients (91 males) with 150 episodes were identified. Haemophilus influenzae was the commonest organism found in sputum (26.0%), followed by Pseudomonas aeruginosa (5.5%), Streptococcus pneumoniae (3.4%), and Moraxella catarrhalis (3.4%). In contrast to most studies from other countries reporting Streptococcus pneumoniae as the most likely bacterial pathogen, Haemophilus influenzae was the commonest bacterium isolated in sputum in this cohort of patients with AECOPD and concomitant pneumonia. / Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. / Exhaled breath condensate (EBC) analysis is a novel tool which has been developed in recent years and the technique is believed to reflect the lower airway lining fluid. My previous work has demonstrated the repeatability of certain inflammatory markers in the EBC of stable asthma and COPD patients. / Hypothesis 1: Bacterial pathogens are the major cause of AECOPD with and without concomitant pneumonia in patients requiring hospitalization. In the one-year retrospective bacteriology study, there were 329 patients with 418 episodes of AECOPD without concomitant pneumonia. These result noted that H. influenzae was the commonest bacterium isolated in sputum in patients with AECOPD without concomitant pneumonia. In areas endemic of tuberculosis, it is advisable to use fluoroquinolones for AECOPD with caution in view of the positive sputum culture of mycobacterium tuberculosis in some patients. / Hypothesis 2: Viral pathogens are an important cause of AECOPD in patients hospitalized with AECOPD. For the prospective infectious aetiology study, there were 643 episodes of AECOPD among 373 patients (307 males). Severe airflow obstruction (stable state spirometry) was associated with a higher chance of positive sputum culture (28.2% for FEV1 &ge;30% vs. 40.4% for FEV1 &lt;30% predicted normal, p=0.006). In this study, Haemophilus influenzae and influenza A were the commonest aetiological agents in patients hospitalized with AECOPD. More severe airflow obstruction was associated with a higher chance of positive sputum culture. / Hypothesis 3: The rates of hospital admissions due to AECOPD are associated with indices of air pollution in Hong Kong. Concerning the effect of air pollutants on AECOPD, significant associations were found between hospital admissions for COPD with all 5 air pollutants. Adverse effects of ambient concentrations of air pollutants on hospitalization rates for COPD are evident, especially during the winter season in Hong Kong. / Hypothesis 4: During the course of AECOPD, it is possible to assess inflammation in the airway by measuring biomarkers non-invasively using the method of EBC collection. To explore the course of inflammation in the airway during AECOPD, 26 patients (22 male) with AECOPD (mean percentage predicted FEV1, 44.8 +/- 14.3), 11 stable COPD and 14 age and sex-matched healthy controls were studied. Repeatability measurements of TNFalpha and LTB4 in 6 stable COPD patients were satisfactory. EBC TNFalpha level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD whereas EBC TNFalpha level was also lower in stable patients receiving ICS post AECOPD than those who were not. These findings suggest a potential role for serial EBC TNFalpha for non-invasive monitoring of disease activity. / Summary. The above studies have shown that bacterial pathogens are the major cause of AECOPD with and without concomitant pneumonia in patients requiring hospitalization and the commonest bacterium found in the sputum of the patients was Haemophilus influenzae. Viral pathogens are also an important cause of AECOPD in patients hospitalized with AECOPD in Hong Kong and the commonest virus identified in the NPA of the patients was influenza A. Concerning the effect of air pollutants on AECOPD, significant associations were found between hospital admissions for AECOPD with the air pollutants of SO2, NO3, O3, PM10 and PM2.5. Finally, TNFalpha could be measured in the EBC of patients during the course of AECOPD and its level was low in patients receiving systemic steroid and antibiotic therapy for AECOPD. The results suggest that it is possible to assess inflammation in the airway by measuring biomarkers non-invasively using the method of EBC collection. (Abstract shortened by UMI.) / Ko, Wai-san Fanny. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0926. / Thesis (M.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 207-250). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.