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.

Orientador: Suzana Erico Tanni / Resumo: Introdução: As manifestações sistêmicas da Doença Pulmonar Obstrutiva Crônica (DPOC) estão relacionadas ao aumento do processo inflamatório sistêmico, entretanto, não está totalmente esclarecido o quanto a inflamação sistêmica, em especial a interleucina-6 (IL-6), está associada com o risco de mortalidade. Dessa forma, o objetivo desse estudo consistiu em avaliar a evolução das concentrações séricas da IL-6 e sua associação com a mortalidade de pacientes com DPOC em nove anos. Pacientes e métodos: 133 pacientes foram avaliados no momento basal entre 2004 e 2006 e reavaliados depois de três e nove anos por meio de avaliação clínica, espirometria, oximetria de pulso e gases arteriais, composição corporal, distância percorrida em seis minutos (DP6), qualidade de vida, intensidade de dispneia, Índice BODE, comorbidades, IL-6 e número de exacerbações nos três primeiros anos de seguimento. Resultados: Durante acompanhamento, 19 pacientes perderam seguimento, quatro não tiveram a causa da morte identificada e 18 estavam com dados incompletos; assim, 92 pacientes foram incluídos na análise de mortalidade tendo a IL-6 como covariável tempo dependente. Na reavaliação dos sobreviventes, 64 pacientes morreram, 23 perderam seguimento, 12 recusaram continuar participando e um não pode ser reavaliado em decorrência de exacerbações frequentes; dessa forma, 33 foram incluídos na reavaliação após nove anos. Sobre o perfil inflamatório, nos pacientes que sobreviveram após nove anos, houve aumen... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD) are related to increased systemic inflammatory process; however, it is not entirely clear how the systemic inflammation, in particular interleukin-6 (IL-6), is associated with mortality risk. Therefore, this study aimed to evaluate the evolution of serum IL-6 concentrations and its association with mortality of COPD patients over nine years. Patients and methods: 133 COPD patients were assessed at baseline between 2004 and 2006 and reassessed after three and nine years through clinical evaluation, spirometry, pulse oximetry and arterial gases, body composition, 6-minute walk distance (6MWD), quality of life, dyspnea intensity, BODE Index, comorbidities, IL-6 and number of exacerbations in the first three years of follow-up. Results: After nine years, 19 patients lost the follow-up, was not possible to identify the date of death of 4 patients and 18 had incomplete data; thus, 92 patients were included in the Cox mortality analysis with IL-6 as a time dependent covariate. In the reassessment of survivors, 64 patients died, 23 lost the follow-up, 12 refused to participate and 1 could not be involved due to recurrent exacerbations; therefore, 33 patients were included in the reassessment after nine years of followup. Regarding the inflammatory profile, in patients who survived after nine years, there was a significant increase in IL-6 [0.4(0.2-0.8) vs 5.7(3.4-11)pg/mL; p<0.001] and reduction in ... (Complete abstract click electronic access below) / Doutor

Assessing the global impact of chronic obstructive pulmonary disease (COPD) on a patient’s life can be difficult to perform in the clinical setting due to time constraints and workflow challenges. The primary objective of this study was to compare disease impact ratings between patient selfadministered COPD Assessment Test (CAT) and physician standard office assessment. This prospective study was conducted at a family medicine residency clinic in northeast Tennessee. The study included two study groups: 1) adult patients seen at the clinic during the 3-month study period with an active diagnosis of COPD, and 2) their physicians. Physicians’ assessment of the impact of COPD on their patients’ daily lives was compared to patients’ self-administered CAT assessments. Physician assessment of COPD impact and patient ssessment of CAT categories significantly differed (χ2 =11.0, P=0.012). There was very poor agreement between patient and physician ratings (κ=0.003), with 42.9% of physician ratings underestimating the impact, 28.6% overestimating the impact, and 28.6% orrectly estimating the impact COPD had on their patients’ lives. These findings support the use of validated assessment tools to help providers understand the symptom burden for patients with COPD.

Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death in the US, and idiopathic pulmonary fibrosis (IPF), a type of Interstitial Lung Disease (ILD), is a fast acting, irreversible disease that leads to mortality within 3-5 years. RNA-sequencing provides the opportunity to quantitatively examine the sequences of millions mRNAs, and offers the potential to gain unprecedented insights into the structure of chronic non-malignant lung disease transcriptome. By identifying changes in splicing and novel loci expression associated with disease, we may be able to gain a better understanding of their pathogenesis, identify novel disease-specific biomarkers, and find better targets for therapy. Using RNA-seq data that our group generated on 281 human lung tissue samples (47=Control, 131=COPD, 103=ILD), I initially defined the transcriptomic landscape of lung tissue by identifying which genes were expressed in each tissue sample. I used a mixture model to separate genes into reliable and not reliable expression. Next, I employed reads that overlapped splice junctions in a linear model interaction term to identify disease-specific differential splicing. I identified alternatively spliced genes between control and disease tissues and validated three (PDGFA, NUMB, SCEL) of these genes with qPCR and nanostring (a hybridization-based barcoding technique used to quantify transcripts). Finally, I implemented and improved a pipeline to perform transcriptome assembly using Cufflinks that led to the identification of 1,855 novel loci that did not overlap with UCSC, Vega, and Ensembl annotations. The loci were classified into potential coding and non-coding loci (191 and 1,664, respectively). Expression analysis revealed that there were 120 IPF-associated and 10 emphysema-associated differentially expressed (q < 0.01) novel loci. RNA-seq provides a high-resolution transcript-level view of the pulmonary transcriptome and its modification in lung disease. It has enabled a new understanding of the lung transcriptome structure because it measures not only the transcripts we know but also the ones we do not know. The approaches and improvements I have employed have identified these novel targets and make possible further downstream functional analysis that could identify better targets for therapy and lead to an even better understanding of chronic lung disease pathogenesis. / 2031-01-01T00:00:00Z

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is one of the leading causes of hospital readmissions within 30 days. Frequent readmissions negatively affect hospital reimbursements and patient outcomes. Creative strategies, such as COPD care bundles, have been shown to reduce readmission rates according to existing studies. A COPD discharge bundle was developed and implemented at 1 community hospital in response to an identified problem with COPD readmissions. Evaluation of this quality improvement initiative was the purpose of this project study. The practice-focused question was: Have 30-day readmission rates changed following the implementation of a COPD discharge bundle prior to transitioning from hospital to home? The framework selected for this project was the model for improvement. Sources of evidence included existing hospital data to evaluate the change in readmissions. The chi-square test of independence was used to assess the difference in frequency of 30-day readmissions. Pre and post-bundle implementation comparisons of readmission rates showed a decrease for 3 out of the 4 groups compared; these results were not statistically significant. Analysis of the post-bundle intervention groups revealed lower 30-day readmissions for individuals who were bundle compliant versus noncompliant and for those who spoke with a pharmacist within 48 hours of discharge opposed to those who did not; these results were statistically significant. Continued use of the bundle and maintaining the role of the pharmacist was recommended. Reduction of readmissions within 30-days has positive social implications for hospitals through financial gains and for the COPD population by improving overall health outcomes.

Chronic obstructive pulmonary disease is the fourth largest cause of death worldwide and the prevalence is predicted to increase even further to make it the third largest cause of death by 2020. The main cause of the disease is exposure to tobacco smoke. COPD is a complex disease and there is a strong need of better understanding of the pathogenetic mechanisms in order to come up with novel therapeutic interventions and preventive strategies. The golden standard to image the lungs today is to use computed tomography (CT) which is an imaging modality that involves ionizing radiation and could thus harm the patient, especially with repeated exposure. New techniques in the image acquisition of magnetic resonance imaging (MRI), an imaging modality that does not involve ionizing radiation, has emerged that allows for lung imaging. The work included segmentation of the lungs, image registration and partitioning of the lungs inorder to perform regional analysis. The results indicate that the mean value of the T1-parameter in the left and right lung is not affected to the same degree, where the left lung showed a greater decrease. The results also showed that the anterior parts of the lungs are not showing any statistically significant changes but the changes were instead seen in the center and posterior parts. Both lungs also showed results that indicate that the mean T1-value is recovered at the end of the longitudinal study, a phenomenon that couldn’t be explained and further studies have to be performed.