Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 116-150.

Thesis (Ph. D.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains xvi, 250 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

Les microARN sont des petits ARN non codants d’une vingtaine de nucléotides qui ont pour fonction de réguler l’expression des gènes en se fixant sur l’extrémité 3’UTR d’ARNm cibles, permettant ainsi leur dégradation ou l’arrêt de leur traduction en protéines. A ce jour, de nombreuses études ont montré l’implication des microARN dans divers processus physiologiques ou pathologiques ; leur rôle dans la réponse de l’organisme aux substances toxiques environnementales commence à être évoqué.La FPI appartient au groupe des pneumopthies interstitielles diffuses idiopathique dont elle est la forme la plus fréquente. Elle se caractérise par la présence de foyers de prolifération de fibroblastes/myofibroblastes responsables d’une production excessive de matrice extracellulaire, une destruction progressive et irréversible de l’architecture pulmonaire entrainant la perte de la fonction respiratoire. L’agression répétée de l’épithélium respiratoire par des composés chimiques environnementaux (ou xénobiotiques) est fortement suspectée dans le déclenchement de la FPI.Le premier objectif de mes travaux de recherche a été d’identifier des microARN susceptibles d’intervenir dans la pathogenèse de la fibrose pulmonaire idiopathique (FPI) et de préciser la (les) fonction(s) de ces microARN d’intérêt. Pour atteindre cet objectif, nous avons étudié deux microARN, le miR-199a-5p et le miR-214-3p qui présentaient la particularité d’être significativement surexprimés dans les poumons de souris souffrant de fibrose pulmonaire. L’analyse systématique des profils d’expression des gènes de fibroblastes surexprimant le miR-199a-5p et le miR-214-3p nous a permis d’identifier un grand nombre de gènes qui étaient significativement modulés par ces deux microARN. Nous avons pu établir l’implication respective du miR-199a-5p et du miR-214-3p dans la régulation de la voie profibrotique TGFβ et dans l’apoptose des fibroblastes pulmonaires médiée par le Fas-ligand. L’ensemble de nos résultats nous permet de suggérer l’utilisation de molécules ciblées contre ces 2 microARN dans le traitement de la FPI.Le second objectif de mes travaux de recherche a été d’identifier le modèle cellulaire in vitro le plus proche du tissu pulmonaire afin d’étudier l’impact des composés toxiques environnementaux sur la pathogenèse des maladies respiratoires et, en particulier, de la FPI. Pour cela, nous avons comparé les profils d’expression génique de l’ensemble des protéines impliquées dans le métabolisme et l’éliminations des xénobiotiques, de 10 lignées cellulaires et de 4 cultures primaires de cellules épithéliales bronchiques humaines, à ceux précédemment observés par notre équipe dans les tissus broncho-pulmonaires humains. L’exposition du modèle cellulaire le plus pertinent à des polluants atmosphériques permettra d’identifier les microARN associés à la toxicité pulmonaire de ces composés chimiques et de vérifier si ces microARN régulent des voies de signalisations communes à celles impliquées dans la pathogenèse de la FPI. / MicroRNAs are small non-coding RNAs with about 20 nucleotides that regulate gene expression by binding to the 3' UTR end of target mRNAs, thus allowing their degradation or stopping their translation into proteins. To date, many studies have shown the involvement of microRNAs in various physiological or pathological processes; their role in the body's response to environmental toxic substances is beginning to be mentioned. It is characterized by the presence of fibroblast/myofibroblast proliferation foci responsible for excessive extracellular matrix production, progressive and irreversible destruction of lung architecture leading to loss of respiratory function. The repeated aggression of the respiratory epithelium by environmental (or xenobiotic) chemicals is strongly suspected in the initiation of IVF. The first objective of my research was to identify microRNAs that may be involved in the pathogenesis of idiopathic pulmonary fibrosis (IVF) and to specify the function(s) of these microRNAs of interest. To achieve this objective, we studied two microRNAs, miR-199a-5p and miR-214-3p, which had the particularity of being significantly overexpressed in the lungs of mice with pulmonary fibrosis. Systematic analysis of the expression profiles of fibroblast genes overexpressing miR-199a-5p and miR-214-3p allowed us to identify a large number of genes that were significantly modulated by these two microRNAs. We were able to establish the respective involvement of miR-199a-5p and miR-214-3p in the regulation of the profibrotic pathway TGFβ and in Fas-ligand mediated apoptosis of pulmonary fibroblasts. The second objective of my research was to identify the in vitro cellular model closest to lung tissue in order to study the impact of environmental toxic compounds on the pathogenesis of respiratory diseases and, in particular, of IVF. To do this, we compared the gene expression profiles of all proteins involved in the metabolism and elimination of xenobiotics, 10 cell lines and 4 primary cultures of human bronchial epithelial cells, with those previously observed by our team in human bronchopulmonary tissues. Exposure of the most relevant cellular model to air pollutants will identify the microRNAs associated with the pulmonary toxicity of these chemical compounds and verify whether these microRNAs regulate signaling pathways common to those involved in the pathogenesis of IVF.

Orientador: Ilma Aparecida Paschoal / Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-16T07:57:21Z (GMT). No. of bitstreams: 1 Veronez_LilianideFatima_M.pdf: 1419140 bytes, checksum: 5e1cf61453007024c5cfed1c82bd88b0 (MD5) Previous issue date: 2010 / Resumo: Objetivos: O objetivo geral deste trabalho foi estudar o uso da capnogragfia volumétrica na avaliação de pacientes portadores de bronquectasias, relacionadas ou não à fibrose cística, para verificar o comportamento de algumas medidas fornecidas pelo aparelho, mais especificamente, analisar a variável "Slope da fase 3" (Slp3) e aquelas relacionadas à caracterização do padrão ventilatório (frequência e tempo expiratório), nos pacientes bronquectásicos, em comparação aos valores obtidos em pacientes normais. Métodos: Foram estudados 24 (vinte e quatro) pacientes com Fibrose Cística e 21 (vinte e um) pacientes não fibrocísticos com bronquectasias idiopáticas, que frequentam o ambulatório de Pneumologia do Hospital de Clínicas da Unicamp. O diagnóstico de Fibrose Cística (FC) foi baseado em 02 (dois) testes de suor, com concentrações de cloro (Cl) alteradas, pelo método de iontoforese por pilocarpina. Os pacientes com bronquectasias foram assim diagnosticados por apresentarem produção crônica de secreção e tomografia computadorizada de alta resolução do tórax (TCAR) com bronquectasias em pelo menos dois segmentos pulmonares. Testes Espirométricos e Capnografia Volumétrica foram feitos. O Grupo Controle foi composto por 114 (cento e quatorze) pacientes não fumantes, sem sintomas e antecedentes de doença respiratória. Resultados: Como resultados, quando comparados o grupo de pacientes com FC com o Grupo Controle, aquele apresentou valores significativos (p<0,05) para Saturação de Oxigênio (SpO2); Frequencia Respiratória (FR); volume expiratório normalizado pelo peso menor (VE/Kg); tempo expiratório (Te) menor e aumento do Slope 3 normalizado pelo volume expirado (P3Slp/Ve). Comparados o grupo de pacientes com Bronquectasias (BQ) com o grupo controle, os resultados significativos (p<0,05) obtidos foram SpO2 menor nos pacientes; FR maior; Ve/Kg menor; Te menor; P3Slop/Ve maior; VCO2 menor. Reunidos os grupos de pacientes (FC e BQ) para comparação com os controles, os pacientes apresentaram valores significativos (p<0,05) para as variáveis, SpO2 menor; FR maior; Ve/Kg menor; Te menor; maior P3Slop/Ve; VCO2 menor. Todas as variáveis capnográficas e espirométricas não mostraram diferenças significativas quando foram comparados os grupos de pacientes fibrocísticos e bronquectásicos. Conclusões: As conclusões foram de que ambos os grupos apresentaram defeitos semelhantes na espirometria (obstrução com concomitante redução da capacidade vital forçada), o padrão respiratório revelado durante a capnografia sugeriu a presença de uma restrição verdadeira (FR alta, Te e Ve baixos e PEF normal). As variáveis capnograficas nos grupos de pacientes mostraram aumentos do slope da fase 3 quando comparados aos controles, fato que provavelmente indica a presença de uma doença difusa de pequenas vias aéreas nas duas doenças, causadora de heterogeneidades de ventilação / Abstract: Objectives: The aim of this study was to use volumetric capnography to evaluate the breathing pattern and ventilation inhomogeneitis in patients with chronic sputum production and bronchiectasis and to correlate the phase 3 slope of the capnographic curve to spirometric measurements. Methods: Twenty-four patients with cystic fibrosis (CF) and 21 patients with non-cystic fibrosis idiopathic bronchiectasis (BC) were serially enrolled.The diagnosis of cystic fibrosis was based on the finding of at least two abnormal sweat chloride concentrations (iontophoresis sweat test). The diagnosis of bronchiectasis was made when the patient had a complaint of chronic sputum production and compatible findings at high resolution computed tomography (HRCT) scan of the thorax.. Spirometric tests and volumetric capnography were performed. One hundred and fourteen subjects of the control group for capnographic variables were non-smokers volunteers, who had no respiratory symptoms whatsoever and no past or present history of lung disease. Results: When compared to controls, patients in CF group had lower SpO2 (p<0.0001), higher respiratory rates (RR) (p<0.0001), smaller expiratory volumes normalized for weight (Ve/kg) (p<0.028), smaller expiratory times (Te) (p<0.0001) and greater phase 3 Slopes normalised for tidal volume (P3Slp/Ve) (p<0.0001). When compared to controls, patients in the BC group had lower SpO2 (p<0.0001), higher RR (p<0.004), smaller Ve/kg (p<0.04), smaller Te(p<0.007), greater P3Slp/Ve (p<0.0001), smaller VCO2 (p<0.0002). The pooled data from the two patient groups, when compared to controls showed that the patients had lower SpO2 (p<0.0001), higher RR (p<0.0001), smaller Ve/kg (p<0.05), smaller Te(p<0.0001), greater P3Slp/Ve (p<0.0001), smaller VCO2 (p<0.0003). All the capnographic and spirometric variables evaluated showed no significant differences between CF and BC patients. Conclusions: Spirometric data in this study reveals that the patients had obstructive defects with concomitant low vital capacities and both groups had very similar abnormalities. The capnographic variables in the patient group suggest a restrictive respiratory pattern (greater respiratory rates, smaller expiratory times and expiratory volumes, normal peak expiratory flows). Both groups of patients showed increased phase III slopes when compared to controls, fact that probably indicates the presence of diffuse disease of small airways in both conditions leading to inhomogeneitis of ventilation / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Orientador: Heloisa Helena de Araújo Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T00:48:21Z (GMT). No. of bitstreams: 1 Mendes_JackelineAmaral_M.pdf: 3206748 bytes, checksum: a2ba24233e4b17f3e6d3d8a4326a499c (MD5) Previous issue date: 2014 / Resumo: Estudos mostram que o sulfeto de hidrogênio (H2S) possui um papel relevante na fisiopatologia de doenças pulmonares. O objetivo deste trabalho foi investigar os mecanismos pelos quais o H2S influência a apoptose, o infiltrado de células inflamatórias, e o remodelamento das vias respiratórias na inflamação alérgica pulmonar. Para isso, camundongos BALB-C foram sensibilizados e desafiados com ovalbunina (OVA). Os camundongos tratados receberam o hidrosulfeto de sódio (NaHS) 30 minutos antes do desafio com OVA (OVA/NaHS). Alguns camundongos sensibilizados receberam salina estéril sem a OVA na ocasião do desafio (grupo salina). A eutanásia dos animais foi realizada 48 horas após o desafio, quando foi coletado o lavado broncoalveolar, para separação imunomagnética de eosinófilos para verificação da apoptose desta célula, e retirados os pulmões. O lobo direito dos pulmões foram homogeneizados para verificação da expressão das proteínas Caspase 3, Caspase 9, Bax, Fas-L e TGF-?1 e para dosagem dos níveis de citocinas. O lobo esquerdo foi fixado no formol para alguns procedimentos de análise histológica. Verificamos o infiltrado inflamatório no parênquima pulmonar pela coloração HE (hematoxilina/eosina) e o colágeno no pulmão utilizando a coloração TM (tricômico de masson). Observamos, também, a apoptose in situ em células epiteliais do pulmão através do ensaio TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling). Por fim, realizamos a imunohistoquímica no pulmão para verificação da expressão das enzimas cistationia-?-liase (CSE) e cistationina-?-sintetase (CBS). Os resultados dos camundongos alérgicos não tratados (OVA) mostraram um aumento do infiltrado inflamatório ao redor dos brônquios e bronquíolos, com prevalência de eosinófilos. O tratamento com NaHS foi efetivo em reduzir este infiltrado inflamatório. No grupo salina não se verificou infiltrado inflamatório. Ao estudarmos a expressão das proteínas Caspase 3, Caspase 9, Fas-L e Bax, observamos que nos animais sensibilizados e desafiados (OVA) a expressão da Caspase 3, Caspase 9 e Bax não sofrem qualquer alteração. No entanto, o tratamento dos animais com NaHS diminui a expressão da Caspase 3, mas não da Caspase 9 e Bax. A expressão do Fas-L é aumentada nos animais sensibilizados e desafiados (OVA) quando comparado ao grupo salina e o tratamento com NaHS diminui essa expressão á níveis semelhantes ao grupo salina. Não foram observadas modificações na apoptose dos eosinófilos isolados dos camundongos alérgicos ou dos tratados com NaHS. Os animais sensibilizados e desafiados apresentaram um aumento da apoptose de células do epitélio brônquico quando comparado ao grupo salina. O tratamento com NaHS foi capaz de reduzir esta apoptose a níveis semelhantes ao grupo salina. Verificamos um aumento dos níveis das citocinas IL-4, IL-5, IL-13 e IL-25 nos pulmões dos camundongos sensibilizados e desafiados, e este aumento foi evitado pelo o tratamento dos animais com NaHS, com exceção da IL-13. A concentração da eotaxina, fator quimiotático de eosinófilos, não sofreu qualquer influência do tratamento com NaHS nos pulmões dos camundongos sensibilizados em resposta ao desafio com OVA. O desafio com OVA aumentou os níveis do IFN-? no homogenato pulmonar, e este aumento foi revertido pelo tratamento dos animais com NaHS a níveis semelhantes aos observados no grupo salina. Os níveis de TNF-? não sofreram alteração do desafio com OVA e nem do tratamento com NaHS. Relacionado ao remodelamento das vias aéreas, não houve formação de colágeno peribronquiolar nos camundongos sensibilizados e desafiados com OVA e nem naqueles tratados com NaHS. O mesmo foi observado na expressão do TGF-?1 que não sofreu influência nem da indução da alergia pulmonar pela OVA nem do tratamento com NaHS. A expressão da enzima CSE tanto no epitélio brônquico como no endotélio vascular estava aumentada nos pulmões dos camundongos alérgicos, e este aumento foi amplificado pelo tratamento com NaHS. Diferentemente da expressão desta enzima, o tratamento com NaHS não modificou a expressão da enzima CBS em nenhuma das estruturas pulmonares estudadas. Em conclusão, nossos resultados sugerem que o H2S tem um efeito protetor no pulmão contra os danos provocados pela alergia. A redução do infiltrado de eosinófilos peribronquiolar pode ser explicada pela diminuição nos níveis pulmonares da IL-4, IL-5 e IL-25, devido à ação do H2S. O H2S também evitou a apoptose e, consequentemente, a destruição do epitélio brônquico, o que contribui para a diminuição da inflamação no processo alérgico pulmonar. A enzima CSE pode estar envolvida neste processo. O H2S possui um importante potencial terapêutico para as doenças alérgicas pulmonares como a asma / Abstract: Many studies show that hydrogen sulfide (H2S) has a relevant role in the pathophysiology of lung diseases. The objective of this study was to investigate the mechanisms by which H2S influence apoptosis, the inflammatory cell infiltrate, and airway remodeling in allergic lung inflammation. To this end, BALB-C mice were sensitized and challenged with ovalbunina (OVA). The treated mice received the sodium hydrosulfide (NaHS) 30 minutes before challenge with OVA (OVA / NaHS). Some sensitized mice received sterile saline without OVA at the time of challenge (saline group). The euthanasia was performed 48 hours after challenge, when it was collected bronchoalveolar lavage for immunomagnetic separation of eosinophils to check this cell apoptosis, and the lungs were removed. The right lobe of the lungs was homogenized for checking the expression of caspase 3, caspase 9, Bax, Fas-L and TGF-?1 protein and for determination of cytokine levels. The left lobe was fixed in formalin for histological analysis. We checked the inflammatory infiltrate in the lung parenchyma by HE staining (hematoxylin/eosin) and collagen in the lung using the TM (Masson trichrome) staining. We also observe in situ apoptosis in lung epithelial cells by TUNEL assay (Terminal deoxynucleotidyl transferase dUTP nick end labeling). Finally, we performed immunohistochemistry in the lung to check the expression of cistationia ?-lyase enzymes (CSE) and cystathionine ?-synthase (CBS). The results of allergy untreated mice (OVA) showed an increase in inflammatory infiltrates around the bronchi and bronchioles, with a prevalence of eosinophils. Treatment with NaHS has been effective in reducing this inflammatory infiltrate. In saline there was no inflammatory infiltrate. By studying the expression of Caspase 3, Caspase 9, Fas-L and Bax proteins, we observed that in animals sensitized and challenged (OVA) the expression of Caspase 3, Caspase 9 and Bax remain unchanged. However, treatment of the animals with NaHS decreases the expression of Caspase 3 but not caspase 9 and Bax. The Fas-L expression is increased in sensitized and challenged (OVA) animals when compared to saline treatment group and NaHS will decrease the expression levels similar to saline group. No changes in apoptosis of eosinophils isolated from allergic mice or those treated with NaHS were observed. The sensitized and challenged animals showed an increase in apoptosis in bronchial epithelial cells as compared to saline group. Treatment with NaHS was able to reduce this apoptosis to similar levels to the saline group. Verified increased levels of IL-4, IL-5, IL-13 and IL-25 in the lungs of sensitized and challenged mice, and this increase was prevented by treating the animals with NaHS, with the exception of IL-13. The concentration of eotaxin, eosinophil chemotactic factor, suffered no influence of treatment with NaHS in the lungs of sensitized in response to challenge with OVA mice. The OVA challenge increased the levels of IFN-? in lung homogenates, and this increase was reversed by treating animals with NaHS levels similar to those observed in the saline group. The levels of TNF-? did not change the OVA challenge nor treatment with NaHS. Related to airway remodeling, there was no formation of peribronchial collagen in mice sensitized and challenged with OVA and not in those treated with NaHS. The same was observed in the expression of TGF-?1 not affected either by the induction of OVA lung allergy or treatment with NaHS. The expression of both enzyme CSE in the bronchial epithelium and the vascular endothelium was increased in the lungs of allergic mice, and this increase was amplified by treatment with NaHS. Unlike the expression of this enzyme, treatment with NaHS did not alter the expression of the enzyme CBS in any of the studied pulmonary structures. In conclusion, our results suggest that H2S has a protective effect against lung damage caused by allergy. The reduced peribronchiolar infiltrate of eosinophils can be explained by the reduction in lung levels of IL-4, IL-5 and IL-25 due to the action of H2S. H2S also avoided apoptosis, and consequently, the destruction of the bronchial epithelium, which contributes to the reduction of pulmonary inflammation in allergic process. The CSE enzyme may be involved in this process. H2S has an important therapeutic potential for allergic pulmonary disorders such as asthma.? / Mestrado / Farmacologia / Mestra em Farmacologia

Orientadores: Maria Elena Guariento, André Fattori / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T14:26:02Z (GMT). No. of bitstreams: 1 Stein_CristianeSerafim_M.pdf: 1514299 bytes, checksum: 40ece1177d3d24a813ac5689ba52c549 (MD5) Previous issue date: 2012 / Resumo: Introdução: Cresce no Brasil e no mundo a prevalência e o impacto das doenças crônicas não transmissíveis. O rápido envelhecimento da população brasileira está associado a esse crescimento e dificulta a efetiva prevenção e tratamento destas doenças e de suas complicações, levando, consequentemente, à perda de autonomia e de qualidade de vida. Entre essas doenças estão as doenças pulmonares crônicas. Numa projeção para as próximas décadas as doenças pulmonares crônicas estarão entre as cinco principais causas de anos de vida perdidos por morte precoce e por incapacidade. O tabagismo aumenta o risco das doenças pulmonares crônicas no adulto e, sobretudo no idoso agrava as alterações fisiológicas próprias do envelhecimento. Uma vez que a doença pulmonar crônica e o tabagismo participam significativamente de um quadro clínico pior, é interessante estudar sua relação com a síndrome da fragilidade, um evento biológico associado à maior vulnerabilidade de agentes estressores e comprometimento da homeostase, principalmente em faixas etárias mais avançadas. Objetivo: Este estudo objetivou investigar a prevalência de doença pulmonar crônica referida em amostra de idosos comunitários e sua relação com tabagismo, índice de massa corporal, sintomas depressivos e fragilidade e seus indicadores. Métodos: Trata-se de um estudo observacional e transversal, de base populacional, do qual participaram 2.315 idosos, com 65 anos e mais. Os dados foram obtidos em seis cidades brasileiras, localizadas nas regiões Norte, Nordeste, Sudeste e Sul, mediante recrutamento feito em domicílios localizados em setores censitários sorteados ao acaso, conforme plano amostral definido previamente, no período de 2.008 e 2.009. Avaliou-se doença pulmonar crônica referida, tabagismo atual e pregresso, bem como o fenótipo de fragilidade, segundo Fried et al, 2.001, em ambos os grupos (com e sem auto relato de doença pulmonar crônica. Constituíram-se quatro grupos para comparação: com autorrelato de doença pulmonar, com e sem tabagismo, separadamente; e outros dois sem o autorrelato de doença pulmonar, também com a presença ou não de tabagismo. As variáveis categóricas foram submetidas à análise de frequência absoluta e percentual. Para comparação das principais variáveis categóricas foram utilizados os testes de qui-quadrado ou exato de Fisher para valores esperados menores que cinco e o teste de Mann-Whitney para comparação de variáveis numéricas entre dois grupos. Para estudar os fatores associados com a presença de doença pulmonar crônica referida foi utilizada a análise de regressão logística univariada e multivariada, com critério stepwise de seleção das variáveis. Para verificar a associação entre doença pulmonar crônica referida e fragilidade, a variável "doença pulmonar crônica" foi selecionada como variável independente. O nível de significância adotado foi de 5% (p<0,05). Resultados: Dos entrevistados 10,8% referiram doença pulmonar crônica e 43% eram fumantes ou ex-fumantes. Verificou-se associação significativa em relação à doença pulmonar crônica referida e índice de massa corporal (com a condição de baixo peso, p<0,001) e com tabagismo (com os ex-fumantes, p<0,001). A análise de regressão logística para fragilidade mostrou associação com doença pulmonar crônica (p<0,001) e a fragilidade em fadiga também se associou com esta enfermidade (p=0,003). Após análise comparativa entre fragilidade (geral e indicadores) entre os quatro grupos formados da combinação entre doença pulmonar crônica referida e tabagismo, verificou-se maior frequência de fragilidade naqueles com doença pulmonar (com ou sem tabagismo), p= 0,013; maior frequência de fragilidade em fadiga nos com doença pulmonar (com ou sem tabagismo), p=0,006; maior frequência de fragilidade em perda de peso nos tabagistas (com ou sem doença pulmonar crônica); e maior frequência de lentidão na marcha nos com doença pulmonar crônica, não tabagistas, p= 0,013. Conclusão: Nesta amostra de população idosa brasileira com doença pulmonar crônica referida evidenciou-se associação desta com a fragilidade, baixo índice de massa corporal e ao ex-tabagismo. Este achado destaca a relevância de se desenvolverem estudos que permitam esclarecer melhor esta associação, bem como desenvolver estratégias que previnam uma piora do quadro e uma evolução para uma condição de fragilidade e seus conhecidos desfechos / Abstract: Introduction: It grows in Brazil and worldwide prevalence and impact of chronic diseases. The rapid aging of the population is associated with this growth and hinders effective prevention and treatment of these diseases and their complications, leading consequently to loss of independence and quality of life. Among these diseases are chronic pulmonary diseases. In a projection for the next decades the chronic pulmonary diseases will be among the top five causes of years of life lost due to premature death and disability. Cigarette smoking increases the risk of chronic pulmonary diseases in adults and especially in the elderly aggravates the physiological changes of aging. Once the chronic pulmonary diseases and smoking significantly participate in a clinical worst, it is interesting to study its relationship with the syndrome of frailty, a biological event associated with greater vulnerability to stressors and impaired homeostasis particularly in older age groups. Objective: This study aimed to investigate the prevalence of chronic pulmonary disease that in a sample of elderly community and its relation to smoking, body mass index, depressive symptoms and frailty and these indicators. Methods: This is an observational, cross-sectional population-based, which involved 2.315 elderly aged 65 years and older. Data were obtained in six Brazilian cities, located in the North, Northeast, Southeast and South, through recruitment done in households located in census tracts drawn randomly sampling plan as defined previously, between 2.008 and 2.009. It was evaluated that chronic pulmonary disease, former and current smoking, as well as the phenotype of frailty, Fried et al., 2.001, in both groups (with and without self-report chronic pulmonary disease. Four groups were formed for comparison: with self-reported pulmonary disease, with and without smoking, separately, and two others without self-reported lung disease, also with the presence or absence of smoking. Categorical variables were analyzed for absolute frequency and percentage. To comparison of the major categorical variables were used chi-square or Fisher exact test for expected values less than five and the Mann-Whitney test for comparison of numerical variables between two groups. To study the factors associated with the presence of chronic pulmonary disease such analysis was used for univariate and multivariate logistic regression with stepwise selection criterion variables. To investigate the association between chronic pulmonary disease and frailty the variable "chronic pulmonary disease" was selected as the independent variable. The significance was 5% (p <0.05). Results: 10.8% reported chronic pulmonary disease and 43% were smokers or former smokers. There was a significant association in relation to chronic pulmonary disease self-reported and the condition of pre-frailty and frailty (58.4% and 9.2% respectively, p = 0.003) and weakness in fatigue (27.8%, p = 0.002). After comparative analysis of frailty (general and indicators) among the four groups formed from the combination of smoking and chronic pulmonary disease self-reported, there was a higher frequency of frailty in those with chronic pulmonary disease (with or without smoking), p = 0.013; higher frequency of frailty in fatigue in those with chronic pulmonary disease (with or without smoking), p = 0.006; higher frequency of frailty in weight loss in smokers (with or without chronic pulmonary disease) and higher frequency of slow march with the chronic pulmonary disease, nonsmokers, p = 0.013. Conclusion: In this sample of Brazilian elderly population with chronic pulmonary disease that showed up this association was with the frailty, low body mass index, former smoking. This finding highlights the importance of developing studies to clarify this association, as well as develop strategies to prevent a worsening of symptoms and a trend for a condition known frailty and its outcomes / Mestrado / Gerontologia / Mestra em Gerontologia

This study was designed to gain an understanding of the family experience when an adult member has chronic obstructive pulmonary disease (COPD). It is recognized that illness within the family affects the well-being of the family unit and the health of all members. To understand the impact of COPD upon the family, however, the literature provides only knowledge of the experience of the individual who has COPD and the spouse, not that of the family unit. Thus, the purpose of this study was to describe and explain the COPD experience from the perspective of the family unit. A qualitative method, phenomenology, was chosen for this investigation. Data were collected through semi-structured interviews with eight families who shared their experiences. From the content analysis of these data, three themes that were common throughout the families' accounts were identified and developed to describe and explain family life with COPD. The first theme, disease-dictated family life, describes four aspects of a common lifestyle that is imposed on the family by the characteristics of COPD. The second theme, isolation, describes the isolation that accompanies the illness experience, for the family group and the individual members within the group. The final theme, family work, describes the four primary challenges the families face and the coping strategies they use to deal with them. These findings revealed that COPD acts as an intense stressor within the family, requiring extensive family work to cope with COPD in a way that maintains the well-being of the family unit. Furthermore, it was found that living with COPD in many ways inhibits the resources within the family and those external sources of support that foster the family's ability to manage the stress associated with living with COPD. The implications for nursing practice and nursing research were delineated in light of the research findings. / Applied Science, Faculty of / Nursing, School of / Graduate

Occupationally-related airway diseases, including asthma and chronic obstructive lung disease, have emerged as having substantial public health importance. The aim of this study was to identify the predictors of occupational sensitisation to grain dust allergens and changes in lung function among grain mill workers in Cape Town. There were two major objectives of the study. Firstly, to determine which of the following factors determine the distribution of serum ECP (eosinophilic cationic protein): age, gender, grain dust exposure, smoking status, atopy and sensitisation to workplace allergens. Secondly, to investigate the risk factors associated with the following outcomes: i) sensitisation to occupational allergens; ii) diagnosis of occupational asthma; iii) diagnosis of chronic obstructive airways disease; and iv) longitudinal changes in lung function. The risk factors studied included age, gender, smoking habits, occupational exposure, lung function status on baseline survey (1989), and allergic sensitisation assessed at follow up (1996). The methods employed involved a repeat measures cross-sectional design including a cohort followed up at different points over a seven year period. Survey instruments included a questionnaire, spirometry and allergy tests (phadiotop, RAST for wheat, rye, Lepidoglyphus destructor, Tyrophagus putrescentiae and Sitophilus granarius). The results indicated an association of grain dust with pulmonary function and allergic sensitisation to grain dust constituents. After adjusting for known confounders such as age, gender and smoking, significant associations were found between employment duration and both decrements in lung function and sensitisation to wheat grain. A decrement of 278 ml in FEY 1 and 328 ml in FYC was associated with occupational sensitisation to wheat (and rye). Increasing employment duration resulted in annual decrements of 18.3 ml in FEY1 and 23 ml in FYC for every year employed. The odds for developing occupational asthma was only mildly elevated (OR=l.35) with increasing employment duration. Age, however, was found to be protective (OR=0.85). Although we were unable to demonstrate a relationship between across-week changes in lung function, at inception, and rapid longitudinal lung function decline, our findings suggested that longitudinal change was related to the degree of airway obstruction at inception. Sensitisation to grain dust allergens was also found to be an independent predictor for FEY 1 and FYC. The prevalence of sensitisation was the highest for wheat (26.4%), followed by Tyrophagus putrescentiae (22.6%), rye (21.7%), Lepidoglyphus destructor (15.1 %) and Sitophilus granarius (15.1 %). Sensitisation to wheat was highly correlated with sensitisation to rye (r = 0.92) and so were Lepidoglyphus destructor and Tyrophagus putrescentiae (r = 0.85). Although a large proportion of the workforce ( 41.5 % ) were sensitised to occupational allergens, the prevalence of respiratory symptoms was between 15.6% and 23.9%. There were 16.7% of workers with health outcomes which fulfilled our criteria for occupational asthma. Atopic workers in our study had at least a nine-fold increased odds of becoming sensitised to grain dust allergens (OR: 8.9-74.7) and a two-fold increased odds of developing occupational asthma (OR= 1.9-84.9). Furthermore, the study found that smokers had a twofold increased odds of becoming atopic, thereby placing them at greater risk of developing respiratory health problems. The mean ECP in this population was 15.4 ug/1 (SD:2.5). Although 45.3% of the workers were atopic, it was not found to be predictor of elevated ECP levels. We were however able to demonstrate a significant association between ECP and sensitisation to grain allergens. Workers sensitised to wheat (positive RAST) had, on average, 1. 78 ug/1 higher ECP levels. The odds of having an elevated ECP (&gt; 15 ug/1) increased by 2.9 for workers sensitised to wheat grain. In conclusion, the results of the study indicate that selection effects are in operation, demonstrating the health worker effect. The findings also suggest that across week reactions may be less sensitive than the across shift changes in predicting rapid longitudinal decline in lung function. While we were able to characterise the distribution of ECP according to exposure, we were however unable to define the temporal relationship between elevated between exposures, ECP and lung function outcomes due to limitations of the study design.

An estimated 45% of all deaths can be attributed to various chronic fibroproliferative diseases. Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease which is characterized by progressive decline in lung function. While the pathogenesis of IPF is not fully understood, alternatively activated macrophages (M2) have been implicated as a key contributor to the fibrotic process. The plasticity of macrophages in vivo challenges the ability to specifically target the M2 macrophage phenotype across species. Previous bioinformatic analysis from our lab identified Dectin-1/Clec7a as a unique marker of M2 macrophages in both human and murine model systems. The expression of the transmembrane receptor Dectin-1 has not been elucidated in the context of pulmonary fibrosis. To prevent the progression of fibrosis by targeting alternatively activated macrophages, we investigated the expression of Dectin-1 in IPF and an experimental model of fibrotic lung disease. Our data demonstrated that while protein expression of Dectin-1 was increased in archived lung tissues of patients with IPF, mRNA expression of this receptor was downregulated in the tissues of these IPF patients. Gene expression of Dectin-1 was shown to be increased in monocyte-derived macrophages, further suggesting a circulatory component contributing to lung fibrosis. As expected, we confirmed that Dectin-1 was highly expressed past the injury phase of the bleomycin-model of induced pulmonary fibrosis which aligns with the increased immune infiltrates at this time point. Preliminary work into the time dependency of the resolution phase of the bleomycin-induced model of lung fibrosis was shown. All in all, our data suggests that Dectin-1 may be a useful marker in characterizing and differentiating phenotypes of macrophages implicated in the fibrotic process. Future efforts aim to gain insight into the functional requirement of Dectin-1 in the alternative activation of profibrotic macrophages to identify novel therapeutic targets for fibrotic lung disease. / Thesis / Master of Science (MSc)

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.