Orientadores: Maria Cecília Bueno Jayme Gallani, Roberta Cunha Matheus Rodrigues / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Enfermagem / Made available in DSpace on 2018-08-26T06:01:11Z (GMT). No. of bitstreams: 1 Miura_CinthyaTamiePassos_D.pdf: 2054944 bytes, checksum: 19f9ca970b1a426cbe265606f08a42d1 (MD5) Previous issue date: 2014 / Resumo: Este estudo teve como objetivo evidenciar a aplicabilidade clínica da versão brasileira do Modified Dyspnea Index (MDI), junto a pacientes portadores de Doença Pulmonar Obstrutiva Crônica (DPOC), a partir da análise de sua validade convergente. Foi verificada a validade convergente do instrumento por meio da correlação com dados da função pulmonar, da capacidade física submáxima, qualidade de vida relacionada à saúde (QVRS) e outra medida de dispneia. Métodos: A coleta de dados foi realizada no período de agosto de 2012 a outubro de 2013, de forma individual, em ambiente privativo, em uma única etapa, por meio de consulta ao prontuário e entrevista individualizada, com aplicação do MDI a seguir dos demais questionários, em sequência aleatória. Posteriormente os pacientes foram submetidos à avaliação da força muscular respiratória, da capacidade funcional e da função pulmonar. A função pulmonar foi analisada por meio da espirometria e da força muscular respiratória. Os seguintes dados foram obtidos a partir da espirometria: volume expiratório forçado no primeiro segundo (VEF1); capacidade vital forçada (CVF) e relação VEF1/CVF. Todos os dados da espirometria foram expressos como valores obtidos e porcentagem do predito. A força muscular respiratória foi avaliada por meio da manovacuometria, sendo mensuradas as pressões inspiratória e expiratória máximas (PI máx e PE máx). A capacidade física submáxima foi avaliada objetivamente por meio do teste de caminhada de 6 minutos (TC6M) e pelo autorrelato, com emprego do instrumento Veterans Specific Activity Questionnaire (VSAQ). A QVRS foi avaliada por meio de uma medida genérica - Medical Outcomes Study Short Form-36 (SF-36), e outra específica para doença pulmonar - versão modificada do Questionário do Hospital Saint George na Doença Respiratória- SGRQm. A Escala Modificada de Borg foi utilizada como outra medida de dispneia. Análise de Dados: Os dados foram submetidos inicialmente à análise descritiva. O teste de correlação parcial, com controle das variáveis: sexo, idade e IMC, foi utilizado para verificar a correlação da versão brasileira do MDI com os valores obtidos na avaliação da função pulmonar, da capacidade física submáxima, da qualidade de vida e da outra medida de dispneia. A análise de outliers uni e multivariados descartou a presença de valores extremos das variáveis de interesse. A correção de Bonferrroni foi adotada com finalidade de evitar os erros do tipo I. Resultados: Correlações positivas, de magnitude modesta a moderada, foram observadas entre o MDI e a capacidade respiratória: VEF1 (r = 0,25, p<0,01) e PI máx (r = 0,36, p<0,01). Correlações positivas, de moderada a forte magnitude, foram observadas com a capacidade física: TC6M ¿ distância (r = 0,34, p<0,01); e VSAQ (r =0,63, p<0,01). Correlação negativa foi observada com a Escala modificada de Borg (dispneia) (r=-0,46, p<0,01). Além disso, fortes correlações positivas foram observadas entre a pontuação total do MDI e medidas de QVRS, especificamente com os domínios de avaliação da capacidade física: SF-36 (r = 0,72, p<0,01) e o SGRQm (r = 0,63, p<0,01). Conclusão: Nossos dados demonstraram evidências de validade convergente da versão brasileira do MDI entre os pacientes com DPOC no Brasil. As correlações observadas apontam para sua utilidade na prática clínica, como avaliação mais abrangente da dispneia / Abstract: This study was aimed at evidencing the clinical applicability of the Brazilian version of the Modified Dyspnea Index (MDI), among Chronic Obstructive Pulmonary Disease (COPD) outpatients by the analyses of its correlations with data regarding pulmonary function; submaximal physical capacity, generic as well as specific measures of health-related quality of life (HRQoL) and another measure of dyspnea. Methods: In this cross-sectional study, data collection was gathred from August 2012 to October 2013, individually, in a private room. Patient records were reviewed and individual interviews were conducted with application of the MDI and then of the other questionnaires, in a random order. Subsequently, patients underwent the assessment of respiratory muscle strength, functional capacity and pulmonary function. Pulmonary function was assessed by spirometry obtaining the following data: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC. All data were expressed as absolute (obtained) values and percentage of predicted. Respiratory muscle strength was assessed through the measures of maximal inspiratory and expiratory pressures (PIM and PEM). The submaximal physical capacity was objectively evaluated by the 6-minute walk test (6MWT) and by the self-reported measure, the Veterans Specific Activity Questionnaire (VSAQ). HRQoL was assessed by a generic measure ¿ the Medical Outcomes Study Short Form-36 (SF-36), and another specific for lung diseases ¿ the Modified Saint George's Respiratory Questionnaire- SGRQm. The Modified Borg Scale was used as another measure of dyspnea. Data Analysis: Data were initially submitted to the descriptive analysis. The partial correlation, adjusted by age, gender and BMI, was used to verify the correlation of the Brazilian version of the MDI with data concerning pulmonary function, submaximal exercise capacity, quality of life and other as dyspnea. Outlier¿s analysis (single or multivariate) discarded the presence of extreme values of the interest variables. The Bonferrroni correction was adopted to control type I errors. Results: Modest to moderate positive correlations were observed between the MDI and respiratory capacity (%): VEF1 (r = .25, p<.01); PIM (r = .36, p<.01). Moderate to strong positive correlations were observed with functional capacity: 6MWT-distance (%) r = .34, p<.01); VSAQ (r = .63, p<.01) and negative correlations with Borg scale (dyspnea) (r = -.46, p<.01). Moreover, strong positive correlations were found between total score of the MDI and HRQoL measures, specifically with the domains concerned to physical capacity: SF-36 (r =.72, p<.01) and SGRQm (r =.63, p<.01). Conclusion: Our data demonstrated evidence of convergent validity of the MDI among Brazilian COPD outpatients. The correlations observed point to the usefulness of the MDI in the clinical practice, as more comprehensive assessment of dyspnea / Doutorado / Enfermagem e Trabalho / Doutora em Enfermagem

Orientador: José Dirceu Ribeiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T22:54:32Z (GMT). No. of bitstreams: 1 Pereira_FabiolaMeister_M.pdf: 3469643 bytes, checksum: b167d6d4404c4180d9e65e29ed5300dd (MD5) Previous issue date: 2011 / Resumo: OBJETIVO: avaliar pacientes com fibrose cística (FC) submetidos ao teste de caminhada de seis minutos (TC6) e compará-los a um grupo controle (GC). MÉTODO: estudo transversal e prospectivo, com indivíduos saudáveis e com FC de um centro universitário de referência. O TC6 foi aplicado de acordo com as normas da ATS e repetido após 30 minutos de repouso. Frequência respiratória (FR), frequência cardíaca (FCr), saturação periférica de oxigênio (SpO2), escala de Borg, status nutricional e valores espirométricos foram analisados. Excluíram-se pacientes em exacerbação pulmonar. O Software SAS System for Windows®, a correlação de Spearman e ANOVA para medidas repetidas foram utilizados, com p<0,05. RESULTADOS: cinquenta e cinco pacientes com FC e 185 indivíduos saudáveis participaram, com idades de 12,2±4,3 e 11,3±4,3 anos, respectivamente. O GC caminhou uma distância maior que o grupo FC em ambos os testes (610,3±53,4m vs. 547,2±80,6m e 616,2±58,0m vs. 552,2±82,1m; p<0,0001). A distância percorrida (DP) se correlacionou com idade, peso e altura. Ambos os grupos caminharam distâncias semelhantes no segundo teste, embora o grupo FC apresentou melhor desempenho no primeiro teste. A SpO2 manteve-se estável durante o teste, com aumento da FCr e da FR. CONCLUSÃO: o TC6 foi capaz de identificar comprometimento funcional em pacientes com FC sem necessidade de repetição imediata do mesmo. Estudos em longo prazo poderão confirmar a utilidade do TC6 como um método barato, eficaz e promissor para acompanhamento da capacidade cardiopulmonar e física de pacientes com FC / Abstract: OBJECTIVE: to evaluate patients with Cystic Fibrosis (CF) submitted to the six minute walk test (6MWT) and compare them to a healthy control group (CG). METHOD: transversal, prospective study comprising patients from a CF university reference centre and in healthy controls. 6MWT was applied accordingly to ATS guidelines and repeated after 30 minutes of rest. Respiratory frequency (RF), heart rate (HR), oxygen saturation (SpO2), Borg scale, nutritional status and spirometry values were analyzed. Patients on pulmonary exacerbation were excluded from the research. The SAS System for Windows® Software, Spearman's correlation and ANOVA for repeated measures were used, with p<0.05. RESULTS: fifty-five CF patients and 185 healthy individuals participated (12.2±4.3 and 11.3±4.3 years, respectively). CG walked a greater distance than the CF patients in both tests (610.3±53.4m x 547.2±80.6m and 616.2±58.0m x 552.2±82.1m; p<0.0001). Walked distance correlated with age, weight and height. Both groups achieved similar distances in the second test, although CF patients had better performance in the first test. The SpO2 maintained stable during the test, with an increase in HR and RF. CONCLUSION: the 6MWT was able to identify functional impairment in CF patients without the immediate need of test repetition. Long-term studies may confirm the use of 6MWT as an easy, cheap and promising tool to follow-up cardiopulmonary and physical capacity of CF patients / Mestrado / Saude da Criança e do Adolescente / Mestre em Ciências

Made available in DSpace on 2014-08-20T13:57:59Z (GMT). No. of bitstreams: 1 Dissertacao_Paula_Oliveira.pdf: 1081819 bytes, checksum: 9e319c71a8b01c131e6f3917156db97d (MD5) Previous issue date: 2012-12-14 / Objective: to evaluate the characteristics of the users of metered-dose inhalers and its prevalence, among those who reported a diagnosis of asthma, bronchitis and/or emphysema. Methods: a population-based study in Pelotas, RS, Brazil, including 3,670 subjects aged 10 years or older. Results: About 10% of the sample referred at least one respiratory disease. Among these, 59% referred symptoms in the last year and of those, only half have used inhalers, showing difference between the quintiles of socioeconomic status (39% poorest quintile vs. 61% richest quintile p=0,01). There was no difference in the use of inhalers by age and sex. Regarding the pharmacological group, the emphysematous used a combination of bronchodilator (BD) plus corticosteroids in greater proportion than just BD. Only among those who reported a medical diagnosis of asthma and with actual symptoms, the proportion of use of inhalers was higher than 50%. Conclusion: metered-dose inhalers are underused among those who relate these diagnoses and the type of medicine used by the ones who referred emphysema is not in accordance with the recommendations in the consensus about these diseases. / Objetivo: avaliar as características dos usuários de inaladores dosimetrados e sua prevalência de uso, entre aqueles que referem diagnóstico de asma, bronquite e/ou enfisema. Métodos: estudo de base populacional realizado em Pelotas, RS, incluindo 3670 indivíduos, com 10 anos de idade ou mais. Resultados: Cerca de 10% da amostra referiu pelo menos uma das doenças respiratórias investigadas. Entre eles, 59% apresentaram sintomas no último ano e, destes, apenas metade usou inaladores, havendo diferença entre os quintis de nível socioeconômico (39% quintil mais pobre vs. 61% no quintil mais rico p=0,01). Não houve diferença no uso de inaladores por sexo e idade. Quanto ao grupo farmacológico, os enfisematosos utilizaram a combinação broncodilatador (BD) + corticoide em maior proporção do que apenas BD. Somente dentre os que referiram diagnóstico médico de asma e sintomas atuais, a proporção de uso de inalador foi maior que 50%. Conclusão: os inaladores dosimetrados são subutilizados entre os que referem estes diagnósticos e que o tipo de medicamento usado por aqueles que referiram enfisema não está de acordo com o preconizado nos consensos sobre estas doenças.

Abstract Lung cancers and chronic obstructive pulmonary disease (COPD) are the most common smoking-related lung diseases and both have high mortality rate. Tight junctions (TJ) are apical junctions between epithelial cells that regulate the permeability of epithelium and form the tight junction along with occludin. Dysfunction of the TJ and dysregulation of TJ proteins leads to a loss of cell-cell adhesion and a loss of cohesion as well as epitheliomesenchymal transition. These increase invasion of lung carcinomas and possibly predispose to the exacerbations in COPD. Therefore, the aim of this thesis was to study expression and regulation of claudins in different lung carcinomas and COPD. Carcinomas expressed claudins 1, 2, 3, 4, 5 and 7 in different variations. Claudin 5 expression was weak in all carcinoma types. Strong claudin 1, 4 and 7 expression was associated with better survival in squamous cell carcinoma and adenocarcinoma. Claudin 3 expression was associated with COPD in large airways. Claudins 3 and 4 was found to be stronger in small airways of smokers and COPD patients than in non-smokers. Transcription factor snail had prognostic value in lung carcinomas. Negative snail expression was associated with longer life expectancy in lung carcinoma patients. Negative snail expression was associated with up-regulated claudin 5 and 7 expression, while strong expression was associated with low claudin 1 and 3 expression. Transcription factors slug and twist were inversely associated with claudins 3 and 4 in small and large airways. Slug expression was higher in non-smokers than in COPD patients and smokers. Transcription factor knockdown increased claudin expression in normal bronchial cell line. Except for claudin 2 and 7, which were decreased. Adenocarcinoma-like cell line was not affected by snail knockdown and in squamous cell carcinoma-like cell line claudin 3, 4 and 7 expression was increased. Transcription factor snail knockdown inhibited invasion of cell lines. Twist knockdown increased transepithelial resistance in normal bronchial cell line indicating higher barrier function in cell layer. / Tiivistelmä Keuhkosyöpä ja keuhkoahtaumatauti ovat yleisiä tupakoinnin aiheuttamia keuhkosairauksia, joissa on korkea kuolleisuus. Tupakointi aiheuttaa muutoksia keuhkojen epiteelisoluissa ja solujen välisissä liitoksissa. Tiivisliitokset solujen välillä säätelevät epiteelin rakennetta ja läpäisevyyttä. Klaudiinit ovat proteiineja, jotka muodostavat tiivisliitoksen yhdessä okkludiinin kanssa. Tiivisliitos proteiinien toimintahäiriöt voivat johtaa solujen välisten liitosten katoamiseen ja epiteelin hajoamiseen sekä epiteelisolujen muuntumiseen mesenkymaalisten solujan kaltaisiksi. Nämä seikat lisäävät invaasiota keuhkosyövissä ja saattavat altistaa pahenemisvaiheisiin keuhkoahtaumataudissa. Väitöskirjassa tutkittiin klaudiinien ilmentymistä ja säätelyä keuhkosyövässä ja keuhkoahtaumataudissa. Klaudiinien1, 2, 3, 4, 5 ja 7 esiintyminen keuhkosyövän histologisissa alatyypeissä vaihteli. Klaudiinien 1, 4 ja 7 voimakas ilmentyminen voitiin yhdistää pidempään elinikään potilailla, joilla oli levyepiteeli- tai adenokarsinooma. Klaudiini 3:n ilmentyminen liittyi keuhkoahtaumatautiin suurissa hengitysteissä. Klaudiinien 3 ja 4 voimakas ilmeneminen pienissä ilmateissä oli yleisempää keuhkoahtaumatautipotilailla ja tupakoitsijoilla kuin tupakoimattomilla henkilöillä. Transkriptiotekijä snailin puuttuminen keuhkosyövässä liittyi potilaiden pidempään elinaikaan. Klaudiinien 5 ja 7 ilmeneminen oli voimakkaampaa, kun snailin määrä oli vähäinen. Klaudiinien 1 ja 3 ilmeneminen väheni snail:in ollessa voimakas keuhkosyövässä. Traskriptiotekijöiden (slug ja twist) ilmeneminen liittyi käänteisesti klaudiinien ilmentymiseen pienissä ja suurissa ilmateissä. Slugin ilmeneminen oli voimakkaampaa tupakoimattomilla henkilöillä kuin tupakoivilla tai keuhkoahtaumatautia sairastavilla. Transkriptiotekijöiden snail, slug ja twist toiminnan estäminen lisäsi klaudiinien määrää normaaleissa keuhkon epiteelisoluissa. Poikkeuksen muodostivat klaudiinit 2 ja 7, joiden määrä väheni kun snail:in toiminta oli estetty. Adenokarsinooma-soluissa snailin estolla ei ollut vaikutusta, ja levyepiteelisyövän soluissa klaudiinien 3, 4 ja 7 määrä kasvoi. Snail myös vähensi solujen invaasiota. Transkriptiotekijä twistin toiminnan esto normaaleissa keuhkoepiteelisoluissa nosti solumaton läpi kulkevan sähkön resistenssiä, mikä on osoitus tiiviistä solujen välisistä liitoksista.

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.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-15T14:33:13Z No. of bitstreams: 1 Gabriel de Assis Cunha Moraes.pdf: 731214 bytes, checksum: b44750e89f86da0b9dbb4c3f5e30fbca (MD5) / Made available in DSpace on 2018-06-15T14:33:13Z (GMT). No. of bitstreams: 1 Gabriel de Assis Cunha Moraes.pdf: 731214 bytes, checksum: b44750e89f86da0b9dbb4c3f5e30fbca (MD5) Previous issue date: 2016-02-23 / Currently, chronic obstructive pulmonary disease (COPD) has an impact on morbidity and mortality throughout the world with high prevalence and a high economic and social cost. It is characterized by slow and progressive airflow limitation, triggered by the inhalation of harmful particles present in cigarette smoke. In this context, several experimental models have been proposed, aiming at the discovery of new therapeutic options. In this regard, low-power laser therapy (LBP) is a relatively new and effective therapy for very low cost, no side effects and possible use in the treatment of chronic pulmonary diseases. In the present study we study some parameters in animals with COPD undergoing therapy diode laser (660 nm), 30 mW, 60 s per point (3 points per application) for 15 days prior to euthanasia. The protocol used for COPD induction consisted of nebulized female C57BL / 6 with cigarette smoke for 75 days (2 times / day). On the day 76, the animals were anesthetized, tracheotomy, canulated and bronchoalveolar lavage (BAL) was collected. Structural and functional parameters were studied, the total and differential counts of cells recovered from BAL fluid, cytokine levels (IL-1 , IL-6, IL-10, IL-17, TNF- and CXCL1/KC) as well as the accumulation of mucus and collagen. It also performed lung histology to quantify the number of lymphocytes in the airway, and bronchial remodeling. Moreover, we will evaluate the expression of the purinergic receptors P2Y2 and P2X7 in the homogenate of lung tissue by Western Blotting technique. The results showed that LLLT significantly reduced the number of total cells in the bronchoalveolar (BAL), the levels of cytokines IL-6, IL-1β, IL-17, TNF-α and CXCL1/KC, mucus production and collagen, cell death, alveolar enlargement, as well as the expression purinergic P2X7 and increased cytokine anti-inflammatory (IL–10). Therefore,we suggested that the laser 808nm is effective to reduce lung inflammation in an experimental model of chronic obstructive pulmonary disease (COPD). / Atualmente a Doença Pulmonar Obstrutiva Crônica (DPOC)apresenta impacto em morbidade e mortalidade em todo o mundo,com alta prevalência e um elevado custo econômico e social. Ela é caracterizada por limitação lenta e progressiva do fluxo aéreo, desencadeado pela inalação de partículas nocivas presente na fumaça do cigarro. Neste contexto, vários modelos experimentais têm sido propostos, objetivando a descoberta de novas opções terapêuticas. Neste sentido, a terapia com Laser de Baixa Potência (LBP) é uma terapia relativamente nova e eficaz, de baixíssimo custo, sem efeitos colaterais e de possível utilização no tratamento das doenças crônicas pulmonares. No presente estudo estudamos alguns parâmetros em animais com DPOC submetidos à terapia com laser de diodo (808nm), 30 mW, 60s por ponto (3 pontos por aplicação) por 15 dias antes da eutanásia. O protocolo utilizado para a indução da DPOC consistiu em nebulizar camundongos fêmeas C57BL/6 com fumaça de cigarro por 75 dias (2 vezes/dia). No dia 76, os animais foram anestesiados, traqueostomizados, canulados e o lavado broncoalveolar (LBA) coletado. Foram estudados parâmetros funcionais e estruturais, como contagem total e diferencial de células recuperadas do LBA, os níveis de citocinas (IL-1, IL-6, IL-10, IL-17, TNF- e CXCL1/KC) bem como o acúmulo de muco e colágeno. Foi realizada também a histologia nos pulmões para a quantificação do número de linfócitos nas vias aéreas, assim como o remodelamento brônquico. Além disso, avaliamos a expressão dos receptores purinérgicos P2X7 e P2Y2 no homogenato do tecido pulmonar por meio da técnica de Western Blotting.Os nossos resultados mostraram que a terapia com laser de baixa potência em um modelo experimental de doença pulmonar obstrutiva crônica (DPOC), diminuiu o número de células no LBA, a produção de citocinas pró-inflamatórias (IL-1β, TNF-α, IL-6, IL-17), quimiocina (CXCL1/KC), produção de muco e colágeno, morte celular, alargamento alveolar, bem como a diminuição da expressão do receptor purinérgico P2X7 e também aumento da citocina anti-inflamatória (IL-10). Portanto, sugerimos que o laser 808nm é eficaz para reduzir a inflamação pulmonar em modelo experimental de doença pulmonar obstrutiva crônica (DPOC).

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-19T17:29:15Z No. of bitstreams: 1 José Carlos Rodrigues Junior.pdf: 971813 bytes, checksum: 62c2be1a3750c4ab8d2efb12f062e157 (MD5) / Made available in DSpace on 2018-07-19T17:29:15Z (GMT). No. of bitstreams: 1 José Carlos Rodrigues Junior.pdf: 971813 bytes, checksum: 62c2be1a3750c4ab8d2efb12f062e157 (MD5) Previous issue date: 2017-12-15 / Introduction: The six-minute walk test (TC6) and shuttle walk test (SWT) are widely used for the assessment of functional capacity in patients with chronic obstructive pulmonary disease (COPD), however their execution may be limited by physical space. In this context, the step test has the facility of being able to be applied in any environment, including the home. However, there are no studies in the literature with constant load tests using the step and its physiological responses. Objectives: 1) to compare the physiological responses between the constant load tests on the cycle ergometer and the endurance step test 2) to establish the determinants of the performance obtained in the TDE, 3) to test the reproducibility of the TDE. Method: 19 patients with COPD performed spirometry, incremental and constant load test on cycle ergometer, bioimpedance to obtain muscle mass and incremental step test (TDI), responded to the Modified Medical Research Council modified dyspnea scale (MRCm) and the Saint George's Respiratory Questionnaire (SGRQ). Leg length was also evaluated and a maximal repetition test was performed. The TDE was performed with 80% of the number of steps obtained in the TDI. This should last for three to eight minutes. If the test time was less than three minutes, the TDE was again performed with 70% of the number of TDI steps. If the TDE was greater than eight minutes, the TDE was performed with a 90% load. Results: there was no difference between the metabolic and ventilatory responses between the TDE and the constant load test in cycle ergometer. No correlation was found between the performance of the TDE with the degree of airway obstruction, mass and quadriceps muscle strength. The time of TDE 90% was shown to be better reproducible compared to TDE 80%. Conclusion: the endurance step test provokes metabolic and ventilatory responses equated to the constant load test on cycle ergometer. / Introdução: O teste de caminhada de seis minutos (TC6) e o shuttle walk test (SWT) são vastamente utilizados para a avaliação da capacidade funcional em pacientes com doença pulmonar obstrutiva crônica (DPOC), entretanto sua execução pode ser limitada pelo espaço físico. Nesse contexto, o teste do degrau possui a facilidade de poder ser aplicado em qualquer ambiente, inclusive o domiciliar. Entretanto, não há na literatura estudos com testes de carga constante utilizando o degrau e suas respostas fisiológicas. Objetivos: 1) comparar as respostas fisiológicas entre os testes de carga constante no cicloergômetro e no teste do degrau endurance (TDE) 2) estabelecer os determinantes do desempenho obtido no TDE, 3) testar a reprodutibilidade do TDE. Método: 19 pacientes com diagnóstico de DPOC realizaram espirometria, teste incremental e de carga constante em cicloergômetro, bioimpedância para obtenção da massa muscular e o teste do degrau incremental (TDI), responderam à escala de dispneia Medical Research Council modificada (MRCm) modificada, e ao Saint George’s Respiratory Questionnaire (SGRQ). Também foi avaliado o comprimento de perna e realizado o teste de uma repetição máxima. O TDE foi realizado com 80% do número de degraus obtido no TDI. Este deverá ter uma duração de três a oito minutos. Caso o tempo do teste fosse menor do que três minutos, o TDE foi novamente realizado com 70% do número de degraus do TDI. Caso o TDE fosse superior a oito minutos, o TDE foi realizado com a carga de 90%. Resultados: não houve diferença entre as respostas metabólicas e ventilatórias entre o TDE e o teste de carga constante em ciclo ergômetro. Não foi encontrada correlação entre o desempenho do TDE com o grau de obstrução de vias aéreas, massa e força muscular de quadríceps. O tempo do TDE 90% mostrou-se com melhor reprodutibilidade, em comparação ao TDE 80%. Conclusão: o teste do degrau endurance provoca respostas metabólicas e ventilatórias equiparadas ao teste de carga constante em cicloergômetro.

Bakgrund: KOL är en allvarlig sjukdom som successivt kan leda till döden. Den största riskfaktorn är rökning, men även annat kan orsaka KOL t.ex. inandning av skadliga ämnen. År 2015 dog 3,17 miljoner av KOL. Studier visar att vården av KOL-patienter idag främst handlar om prevention och rehabilitering. Sällan tas patienternas upplevelser och erfarenheter i akt.Syfte: Syftet med denna litteraturstudie var att undersöka upplevelser och erfarenheter av KOL-patienter och hur det påverkar deras dagliga liv.Metod: En litteraturstudie med kvalitativ ansats som baserades på 11 vetenskapliga artiklar. Litteratursökningen genomfördes i databaserna PubMed och CINAHL. Utvalda artiklar granskades utifrån SBU:s mall för kvalitetsgranskning. Metasyntes av icke strukturerad karaktär användes som metod för att analysera data. Resultat: Utifrån data som samlats in går det att urskilja att andningen är den centrala faktorn som påverkar patienternas dagliga liv. Andfåddheten för med sig andra konsekvenser. Sex teman identifierades: “Sjukdomsinsikt och förnekelse”, “Acceptans och hanteringsstrategier”, “Vård som en del av vardagen”, “Psykiskt lidande”, “Begränsningar och påverkan på det sociala livet och familjelivet” och “Hopp om framtiden”.Konklusion: Patienternas behov varierar mycket. Detta betyder att vården behöver vara enad och samarbeta för att bedriva en personcentrerad vård. Sjuksköterskans roll och bemötande är viktigt för det patientnära omvårdnadsarbetet och i rollen som kontaktperson för KOL-patienter. / Background: COPD is a grave illness which potentially leads to an early death. The greatest determinant is smoking, but there are other factors that can lead to COPD. Inhaling hazardous materials would be one example. In 2015, 3,17 million people worldwide died due to COPD. Studies show that the medical care for COPD-patients today is primarily focused on prevention and rehabilitation. Concern for the patient's own experiences are rare. Aim: The aim of this literature review was to examine the experiences of COPD-patients and the effects on their daily lives from the illness.Method: A literature review with a qualitative approach, based on 11 scientific articles. The databases used for the article searching were PubMed and CINAHL. Chosen articles were quality controlled by SBU’s model for quality reviewing. A non-structured meta synthesis was used for analysing data.Result: The data presented by the included articles all showed how the patients breathing ability is the central factor in their lived experiences. Breathlessness brought consequences. Six themes emerged: “Illness and Denial”, “Acceptance and Coping Strategies”, “Health Care as a part of Everyday Life”, “Mental Suffering” and “Hope for the Future”.Conclusion: The patients' health care needs varied considerably. This gives reason for the health care unit to be united in the work for person centered care. The nurse’s role and response to patients are important for the close to patient care and profession role as contact person for COPD patients.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13327号 / 論医博第2195号 / 新制||医||1044(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 古川 壽亮, 教授 伊達 洋至, 教授 佐藤 俊哉 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Kronisk obstruktiv lungsjukdom (KOL) är en progressiv och obotlig sjukdom som påverkar andningsfunktionen och orsakar lidande. Sjukdomen medför ett stort behov av hälso- och sjukvård och leder till stora samhällskostnader. Vården skall utgå från ett personcentrerat förhållningssätt och i formen av multidisciplinära team med syfte att främja patientens förmåga att själv hantera sin sjukdom i den grad som är möjligt. Syftet med litteraturstudien var att undersöka patienters upplevelser av att leva med KOL. Metoden var en litteraturstudie med tio vetenskapliga artiklar som analyserades med hjälp av en fem stegs-modell. Resultatet presenterades i fyra teman: Vardagen begränsas av KOL, Coping-strategier är viktiga för att hantera sjukdomen, Upplevelser av välmående vid KOL och Upplevelser av stödbehov. Slutsatsen är att KOL är en sjukdom som begränsar livet i stor utsträckning och leder till upplevelser av förlorad hälsa och välmående. För att hantera begränsningarna är det viktigt att använda coping-strategier. Sjukdomen medför också ett stort stödbehov som tillgodoses av närstående, sjukvården och samhället. / Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible disease that affects the respiratory function and causes suffering. The disease contributes to a significant need of healthcare and constitutes a large cost to society. The care needs to come from a person-centered perspective and in the form of multidisciplinary team with the purpose of promoting the patient's ability to manage their disease as well as possible. The aim of this literature study was to examine the patients experiences of living with COPD. The method was a literature study with ten scientific articles who were analyzed with the help of a five step-model. The result is presented in four themes: Everyday life limited by COPD, Coping- strategies are important to manage the disease, Experiences of wellbeing with COPD and Experiences of support needs. The conclusion is that COPD is a disease which limits the daily life greatly and contributes to experiences of lost health and wellbeing. To manage the limitations, it is important to use coping-strategies. The disease also entails a great need of support which can be met by the relatives, the healthcare system and the community.