A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma doença caracterizada pela limitação ao fluxo aéreo, não totalmente reversível. Dentre as terapêuticas indicadas, a reabilitação pulmonar é uma estratégia de tratamento multidisciplinar, que tem por objetivo melhorar a qualidade de vida do paciente, reintegrando-o à sociedade. Objetivos: Descrever o processo e os custos de implantação na forma de um projeto de extensão universitária, os motivos da evasão e os resultados obtidos com um programa de reabilitação pulmonar. Material e Métodos: Após formar um grupo multidisciplinar no Centro Universitário Feevale e estabelecer uma parceria com a Secretaria Municipal da Saúde de Novo Hamburgo, os pacientes portadores de DPOC são encaminhados ao programa de reabilitação pulmonar (PRP). São avaliados pelo médico pneumologista, fisioterapeuta, nutricionista, psicólogo e educador físico. Após estas avaliações são formados grupos de até 16 pacientes que permanecem por um período de 4 meses, com três sessões semanais de treinamento físico, orientações nutricionais, encontros educativos e grupos de apoio psicológico. Foram avaliados o perfil destes pacientes, os custos para a implantação, as causas de evasão após o início do programa, bem como os resultados obtidos após o período de tratamento, medidos através do teste de caminhada dos seis minutos, do trabalho de caminhada através do produto distância-peso corporal e do questionário Saint George de qualidade de vida. Para a análise dos resultados foi utilizada a estatística descritiva, para comparação das médias o Teste t de Student. Resultados: O PRP foi implantado na forma de um projeto de extensão universitária, com um custo total de R$ 64 224,60. Foram avaliados 134 pacientes encaminhados dos postos de saúde do município de Novo Hamburgo e dos municípios vizinhos. Do total, 38 (28,4%) pacientes foram excluídos e 7(5,2%) foram a óbito antes de completar a avaliação. Desses, 89 (66,5%) portadores de DPOC de moderado a grave foram incluídos no PRP. A média de idade dos pacientes foi de 63,5±9,9 anos, predominou o sexo masculino 62(69%), com índice de massa corporal (IMC) médio de 23,5±5,3 Kg/m2, com média de Volume expiratório forçado no primeiro segundo (VEF1) de 1,16L(42,8±23,4% do previsto). Dos incluídos no PRP, 40 (44,9%) abandonaram, principalmente por problemas sócio-econômicos e 49 (55,1%) concluíram a reabilitação. Os dados para análise antes e depois do PRP estavam disponíveis para 37 pacientes que formaramo grupo para analisar os resultados do PRP. No teste de caminhada dos seis minutos, ocorreu uma variação significativa de 34,12m na média distância (367,15±101,93m vs. 401,27±95,55m; p <0,001). Ocorreu melhora significativa de 2,65 Km.Kg-1 (24,36±9,62 Km.Kg-1 vs. 27,01±10,0 Km.Kg-1) no trabalho de caminhada medido pelo produto distância-peso e uma melhora significativa com redução de 11% (46 vs. 35; p<0,001) no total do questionário Saint George de qualidade de vida. Conclusões: O PRP pode ser implantado na forma de um projeto de extensão universitária, com custo relativamente baixo pela sua abrangência e benefícios. A condição social dos pacientes foi o maior determinante da evasão, mas os pacientes que concluíram o PRP apresentaram uma melhora significativa na sua capacidade de exercício e na qualidade de vida. / Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible airway obstruction. Pulmonary rehabilitation is one of the therapeutic interventions indicated for the treatment of COPD, and consists of a multidisciplinary treatment strategy whose purpose is to improve quality of life and to reintegrate patients into society. Objective: To describe the process and cost of implementing a university extension program for pulmonary rehabilitation, as well as the causes of patient dropout and the results achieved. Material and methods: After a multidisciplinary group was formed at Centro Universitário Feevale and a partnership was established with the Municipal Department of Health of Novo Hamburgo, patients with COPD were referred to the pulmonary rehabilitation program (PRP). They were examined by a pulmonologist, a physical therapist, a nutritionist, a psychologist and a physical education specialist. After evaluations, groups of up to 16 patients were formed and had 3 weekly meetings for 4 months. During meetings, patients participated in physical exercise training, nutritional counseling, educational meetings and psychological support groups. We evaluated patient data, costs of program implementation and causes of patient dropout. Also, the results obtained after PRP were measured by the 6-minute walk test, work calculated as the product of distance x body weight, and the St George respiratory questionnaire to assess quality of life. Descriptive statistics was used to analyze results, and the Student t test, to compare means. Results: PRP was implemented as a university extension program at a total cost of R$ 64,224.60. One hundred thirty-four patients referred by health stations in Novo Hamburgo and neighboring cities were evaluated; 38 (28.4%) of these patients were excluded and 7 (5.2%) died before they completed the initial evaluation. The other 89 (66.5%) patients with moderate to severe COPD were included in PRP. Mean patient age was 63.5±9.9, 62 (69%) were men, mean body mass index (BMI) was 23.5±5.3 kg/m2, and mean forced expiratory volume in one second (FEV1) was 1.16 L (42.8±23.4% of predict value). Forty (44.9%) patients dropped out, most of them due to socioeconomic problems, and 49 (55.1%) completed the rehabilitation program. Data for the analysis before and after PRP were available for 37 patients, who formed the group for analysis of PRP results. The 6-minute walk test showed a significant increase of 34.12 m in distance(367.15±101.93 m vs. 401.27±95.55 m; p <0.001). A significant improvement of 2.65 km.kg-1 (24.36±9.62 km.kg-1 vs. 27.01±10.0 km.kg-1) was observed in distance x body weight product, and total scores of the St. George questionnaire showed a reduction of 11% (46 vs. 35; p<0.001), which indicated a significant improvement in quality of life. Conclusion: PRP was implemented as a university extension program at a relatively low cost when considering its extent and benefits. Social condition was the main cause of patient dropout, but those that completed PRP had a significant improvement in their capacity for physical exercise and in quality of life.

A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma doença caracterizada pela limitação ao fluxo aéreo, não totalmente reversível. Dentre as terapêuticas indicadas, a reabilitação pulmonar é uma estratégia de tratamento multidisciplinar, que tem por objetivo melhorar a qualidade de vida do paciente, reintegrando-o à sociedade. Objetivos: Descrever o processo e os custos de implantação na forma de um projeto de extensão universitária, os motivos da evasão e os resultados obtidos com um programa de reabilitação pulmonar. Material e Métodos: Após formar um grupo multidisciplinar no Centro Universitário Feevale e estabelecer uma parceria com a Secretaria Municipal da Saúde de Novo Hamburgo, os pacientes portadores de DPOC são encaminhados ao programa de reabilitação pulmonar (PRP). São avaliados pelo médico pneumologista, fisioterapeuta, nutricionista, psicólogo e educador físico. Após estas avaliações são formados grupos de até 16 pacientes que permanecem por um período de 4 meses, com três sessões semanais de treinamento físico, orientações nutricionais, encontros educativos e grupos de apoio psicológico. Foram avaliados o perfil destes pacientes, os custos para a implantação, as causas de evasão após o início do programa, bem como os resultados obtidos após o período de tratamento, medidos através do teste de caminhada dos seis minutos, do trabalho de caminhada através do produto distância-peso corporal e do questionário Saint George de qualidade de vida. Para a análise dos resultados foi utilizada a estatística descritiva, para comparação das médias o Teste t de Student. Resultados: O PRP foi implantado na forma de um projeto de extensão universitária, com um custo total de R$ 64 224,60. Foram avaliados 134 pacientes encaminhados dos postos de saúde do município de Novo Hamburgo e dos municípios vizinhos. Do total, 38 (28,4%) pacientes foram excluídos e 7(5,2%) foram a óbito antes de completar a avaliação. Desses, 89 (66,5%) portadores de DPOC de moderado a grave foram incluídos no PRP. A média de idade dos pacientes foi de 63,5±9,9 anos, predominou o sexo masculino 62(69%), com índice de massa corporal (IMC) médio de 23,5±5,3 Kg/m2, com média de Volume expiratório forçado no primeiro segundo (VEF1) de 1,16L(42,8±23,4% do previsto). Dos incluídos no PRP, 40 (44,9%) abandonaram, principalmente por problemas sócio-econômicos e 49 (55,1%) concluíram a reabilitação. Os dados para análise antes e depois do PRP estavam disponíveis para 37 pacientes que formaramo grupo para analisar os resultados do PRP. No teste de caminhada dos seis minutos, ocorreu uma variação significativa de 34,12m na média distância (367,15±101,93m vs. 401,27±95,55m; p <0,001). Ocorreu melhora significativa de 2,65 Km.Kg-1 (24,36±9,62 Km.Kg-1 vs. 27,01±10,0 Km.Kg-1) no trabalho de caminhada medido pelo produto distância-peso e uma melhora significativa com redução de 11% (46 vs. 35; p<0,001) no total do questionário Saint George de qualidade de vida. Conclusões: O PRP pode ser implantado na forma de um projeto de extensão universitária, com custo relativamente baixo pela sua abrangência e benefícios. A condição social dos pacientes foi o maior determinante da evasão, mas os pacientes que concluíram o PRP apresentaram uma melhora significativa na sua capacidade de exercício e na qualidade de vida. / Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible airway obstruction. Pulmonary rehabilitation is one of the therapeutic interventions indicated for the treatment of COPD, and consists of a multidisciplinary treatment strategy whose purpose is to improve quality of life and to reintegrate patients into society. Objective: To describe the process and cost of implementing a university extension program for pulmonary rehabilitation, as well as the causes of patient dropout and the results achieved. Material and methods: After a multidisciplinary group was formed at Centro Universitário Feevale and a partnership was established with the Municipal Department of Health of Novo Hamburgo, patients with COPD were referred to the pulmonary rehabilitation program (PRP). They were examined by a pulmonologist, a physical therapist, a nutritionist, a psychologist and a physical education specialist. After evaluations, groups of up to 16 patients were formed and had 3 weekly meetings for 4 months. During meetings, patients participated in physical exercise training, nutritional counseling, educational meetings and psychological support groups. We evaluated patient data, costs of program implementation and causes of patient dropout. Also, the results obtained after PRP were measured by the 6-minute walk test, work calculated as the product of distance x body weight, and the St George respiratory questionnaire to assess quality of life. Descriptive statistics was used to analyze results, and the Student t test, to compare means. Results: PRP was implemented as a university extension program at a total cost of R$ 64,224.60. One hundred thirty-four patients referred by health stations in Novo Hamburgo and neighboring cities were evaluated; 38 (28.4%) of these patients were excluded and 7 (5.2%) died before they completed the initial evaluation. The other 89 (66.5%) patients with moderate to severe COPD were included in PRP. Mean patient age was 63.5±9.9, 62 (69%) were men, mean body mass index (BMI) was 23.5±5.3 kg/m2, and mean forced expiratory volume in one second (FEV1) was 1.16 L (42.8±23.4% of predict value). Forty (44.9%) patients dropped out, most of them due to socioeconomic problems, and 49 (55.1%) completed the rehabilitation program. Data for the analysis before and after PRP were available for 37 patients, who formed the group for analysis of PRP results. The 6-minute walk test showed a significant increase of 34.12 m in distance(367.15±101.93 m vs. 401.27±95.55 m; p <0.001). A significant improvement of 2.65 km.kg-1 (24.36±9.62 km.kg-1 vs. 27.01±10.0 km.kg-1) was observed in distance x body weight product, and total scores of the St. George questionnaire showed a reduction of 11% (46 vs. 35; p<0.001), which indicated a significant improvement in quality of life. Conclusion: PRP was implemented as a university extension program at a relatively low cost when considering its extent and benefits. Social condition was the main cause of patient dropout, but those that completed PRP had a significant improvement in their capacity for physical exercise and in quality of life.

Introdução: A Doença Pulmonar Obstrutiva Crônica (DPOC) está associada a uma resposta inflamatória anormal dos pulmões com consequências sistêmicas. A espirometria parece não ser suficiente para acompanhamento das alterações sistêmicas, que pode ser auxiliada por marcadores sanguíneos de inflamação. Não há consenso sobre a participação da proteína Creativa (PCR) nesse processo. Objetivo: Nosso objetivo foi verificar a relação entre a PCR, como marcador inflamatório, e as alterações musculares sistêmicas da doença: qualidade de vida, capacidade funcional, força muscular respiratória e periférica em pacientes portadores de DPOC. Métodos: Foram avaliados sessenta e dois pacientes não internados com doença pulmonar obstrutiva crônica estável, mediante a determinação da pressão inspiratória máxima (PI máx.), pressão expiratória máxima (PE máx.), teste de caminhada de seis minutos (TC6), dinamometria de membros superiores, função pulmonar à espirometria, manovacuometria, questionário de qualidade de vida do Hospital Saint George (SGRQ) e PCR. Resultados: Para avaliar a associação entre as variáveis contínuas, foram aplicados os coeficientes de correlação de Pearson (r) ou Spearman (rs), sendo encontrada correlação da PCR com as seguintes variáveis: item de domínio “sintomas” (SG), rs= - 0,410 e p= 0,003 e idade dos pacientes, rs= 0,318 e p= 0,042 para p<0,05. Conclusão: Concluímos que a proteína C-reativa correlaciona-se com o item de domínio “sintomas” do SGRQ e com a idade em portadores de DPOC, quando não incluídos em episódio agudo dos sintomas e que passe a ser considerada para a avaliação do fator inflamação sistêmica, em permanência nesses pacientes. / Introduction: Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal inflammatory response of the lungs with systemic consequences. Spirometry is not sufficient to monitor systemic changes that might be aided by blood markers of inflammation. There is no consensus on the involvement of C-reactive protein (CRP) in the process. Objective: Our objective was to assess the relationship between CRP as an inflammatory marker and systemic muscular changes of CPOD: quality of life, functional capacity, peripheral muscle strength and respiratory muscle strength. Methods: Were assessed 62 outpatients with stable chronic obstructive pulmonary disease, by determining the maximum inspiratory pressure (PI max.), maximum expiratory pressure (PE max.), six-minute walk test (6MWT), grip strength test using dynamometer, lung function with spirometry, manovacuometry, Saint George Respiratory Questionnaire (SGRQ) and CRP. Results: To assess the correlation between continuous variables, we applied the Pearson correlation coefficient (r) or Spearman coefficient (rs). We found correlation of PCR with the following variables: "symptoms" domain item (SG), rs= - 0,410 and p = 0.003, and patient age, rs= 0,318 and p = 0.042 with p <0.05. Conclusion: We conclude that C-reactive protein correlates itself with the "symptoms" domain item of the SGRQ and with age in patients with COPD, when not included in symptoms acute episodes. We suggest that PCR starts to be considered for the evaluation of systemic inflammation factor, always present in these patients.

Existe uma relação anatômica e funcional entre a respiração e a deglutição, sendo essencial a coordenação temporal entre essas duas funções para manter a ventilação e prevenir a aspiração pulmonar. Alterações no padrão da respiração e da ventilação podem influenciar a coordenação entre deglutição e respiração. Pacientes com doenças pulmonares crônicas podem ser susceptíveis a apresentar alteração na coordenação entre deglutição e respiração devido às alterações funcionais ventilatórias. O objetivo desta dissertação foi identificar sintomas de disfagia em indivíduos com doença pulmonar obstrutiva crônica (DPOC), por meio da aplicação de um questionário de triagem de disfagia. Foram avaliados 35 pacientes portadores de DPOC e 35 participantes voluntários pareados por idade e gênero. A caracterização dos participantes do grupo com a DPOC foi realizada pela gravidade da doença (VEF1) e pela dispnéia (escala MMRC). O índice de massa corpórea foi calculado para os participantes de ambos os grupos. A identificação dos sintomas de disfagia foi realizada por meio da aplicação de um questionário de triagem de disfagia. Os participantes com DPOC apresentaram sintomas moderados (p<0,001) e leves (p<0,003) de disfagia quando comparados aos indivíduos sem a doença. A Análise Fatorial permitiu agrupar em fatores as questões que possuíam significados em comum, reduzindo a quantidade de variáveis do estudo. Foram determinados 4 fatores que totalizaram 63,5% da variabilidade da amostra: Fator I - relacionado a função faríngea e proteção da via aérea; Fator II: relacionado a função esofágica e história de pneumonia ; Fator III: relacionado ao estado nutricional; Fator IV: relacionado a função oral. Os sintomas mais freqüentes de disfagia apresentados pelos participantes com DPOC foram relacionados aos fatores: função faríngea e proteção de via aérea (p<0,001); função esofágica e história de pneumonia (p<0,001) e estado nutricional (p<0,001). A variável IMC correlacionou-se com o VEF1 (r=0,567;p<0;001) e com estado nutricional (r= -0,046; p<0,008). A dispnéia correlacionou-se com a função faríngea e proteção de via aérea (r=0,408;p=0,015) e com a função esofágica e história de pneumonia (r= 0,397; p<0,015). O fator função faríngea e proteção da via aérea correlacionou-se com o fator função esofágica e história de pneumonia (r= 0,531; p=0,001). Conclusão: Indivíduos com DPOC apresentam sintomas de disfagia quando comparados a grupo controle. / There is an anatomical and physiological relationship between breathing and swallowing, the temporal coordination between these two functions are essential to maintain ventilation and to prevent pulmonary aspiration. Changes in the breathing and ventilation patterns can have an influence on the coordination of swallowing and respiration. Patients with chronic lung diseases may be susceptible to changes in the coordination between swallowing and breathing due to ventilatory functional changes. The purpose of this research was to identify symptoms of dysphagia in patients with chronic obstructive pulmonary disease (COPD), through the application of a screening questionnaire for dysphagia. Participants of the research were 35 patients with COPD and 35 control volunteers matched by age and gender. The characterization of the participants in the group with COPD was conducted by disease severity (FEV1) and dyspnea (MMRC scale). The body mass index was calculated for participants in both groups. The identification of the symptoms of dysphagia was achieved by applying a screening questionnaire for dysphagia. Participants with COPD had moderate symptoms (p<0,001) and mild symptoms (p<0,003) of dysphagia when compared to subjects without the disease. The factor analysis allowed grouping in factors the questions that had meanings in common, reducing the amount of study variables. It was determined that four factors totaled 63,5% of the variability of the sample: Factor I - related to pharyngeal function and airway protection; Factor II: related to esophageal function and history of pneumonia; Factor III: related to nutritional status; Factor IV: related to oral function. The most frequent symptoms of dysphagia presented by the participants with COPD were related to factors: pharyngeal function and airway protection (p<0,001); esophageal function and history of pneumonia (p<0,001); and nutritional status (p<0,001). The BMI correlated with FEV1 (r=0,567;p<0;001) and nutritional state (r= -0,046; p<0,008). Dyspnea correlated with pharyngeal function and airway protection (r=0,408;p=0,015) and with esophageal function and history of pneumonia (r= 0,397; p<0,015). Pharyngeal function and airway protection correlated with esophageal function and history of pneumonia (r= 0,531; p=0,001). Conclusion: Participants with COPD had symptoms of dysphagia when compared to control group.

A doença pulmonar obstrutiva crônica (DPOC) promove limitações mecânicas e encurtamento muscular que determinam a elevação do tórax, o aumento do volume residual e da capacidade residual funcional dos pulmões. Alterações do padrão torácico e na complacência pulmonar se correlacionar com as funções estomatognáticas por meio do osso hióide e da mandíbula. O objetivo deste estudo foi analisar a influência das desordens respiratórias decorrentes da DPOC no sistema estomatognático por meio de análise eletromiográfica. Participaram do estudo 40 indivíduos de ambos os gêneros com idade entre 40 e 80 anos, divididos em dois grupos: GD, grupo DPOC (n=20), média de idade de 65,65±8,11 anos e IMC de 24,92±2,97, estádio GOLD II a IV; e GC, grupo controle (n=20), idade média de 65,80±8,18 anos e IMC de 26,19±2,38, composto por indivíduos sem a doença. Os indivíduos foram submetidos as avaliações de eletromiografia de superfície para análise dos músculos do sistema respiratório e estomatognático; e força muscular respiratória por meio da manovacuometria. Os valores obtidos foram normalizados, tabulados e submetidos à análise estatística (SPSS versão 22.0) por meio do test t-student de amostras independentes (p<0,05). Em relação aos resultados, o sistema respiratório apresentou diferenças significativas (p<0,05) entre o GD e GC, em especial para o músculo diafragma nas condições clínicas de repouso, ciclo respiratório e inspiração máxima com menor atividade das fibras musculares, expiração máxima com maior atividade e redução da força muscular respiratória. O sistema estomatognático apresentou maior atividade (p<0,05) das fibras dos músculos masseteres nas condições clínicas de repouso e protrusão, e na lateralidade esquerda para os músculos temporal e esternocleidomastoideo direito, quando comparados os grupos GD e GC. Sugere-se, que as alterações encontradas na atividade do músculo diafragma decorrentes da restrição da mobilidade torácica, parecem estar relacionadas com alterações nas condições posturais da mandíbula, ocasionando aumento na atividade das fibras musculares relacionadas ao sistema estomatognático de indivíduos com DPOC. / Chronic obstructive pulmonary disease (COPD) promotes mechanical limitations and muscle shortening that determine chest elevation, leading to increased residual volume and functional residual capacity of the lungs. Changes in the thoracic pattern and pulmonary complacency are related to the stomatognathic functions through the hyoid bone and the mandible. We aimed to analyze the influence of respiratory disorders due to chronic obstructive pulmonary disease in the stomatognathic system. We divided 40 participants of both genders, ranging from 40 to 80 years old, into two groups: DG, COPD group (n = 20), average age 65.65 ± 8.11 years and body mass index (BMI) 24.92 ± 2.97, GOLD II to IV; and CG, control group (n=20), average age 65.80 ± 8.18 years and BMI 26.19 ± 2.38, composed of individuals without the disease. The participants underwent respiratory and stomatognathic surface electromyography evaluations, and respiratory muscle strength tests through manovacuometry. The values were subjected to t-student test of independent samples (p<0.05). The respiratory system showed significant alterations (p<0.05) between the DG and CG groups, especially for the diaphragm muscles in the clinical conditions of rest, respiratory cycle, and maximal inspiration with a lower recruitment of muscle fibers, greater muscle activity during maximal expiration, and reduction of respiratory muscle strength. The stomatognathic system indicated greater activity (p<0.05) in the recruitment of the fibers of the masseter in the clinical conditions of rest and protrusion, and in the left laterality to the temporal and right sternocleidomastoid muscles, when comparing the DG and CG groups. It was concluded that alterations in diaphragm muscle activity influence the postural conditions of the mandible due to the restriction of thoracic mobility, causing an increase in the recruitment of muscle fibers related to the stomatognathic system in individuals with COPD.

Le remodelage bronchique regroupe des entités physiopaphologiques commel’hypertrophie musculaire lisse dans l’asthme ou l’augmentation d’épaisseur bronchique surl’infiltration de cellules inflammatoires et l’accumulation de fibrose dans la BPCO. Cesremodelages sont corrélés à l’obstruction fonctionnelle et donc à la sévèrité de ces maladies.L’analyse de biopsies bronchique ou pulmonaire permet d’étudier ce phénoméne qui, aprèsune meilleure compréhension, est une cible thérapeutique intérressante. Le premier articleest une revue d’indications de bronchoscopie chez les patients de réanimation. La deuxièmeétude a montré une augmentation des fibrocytes sanguins au cours d’exacerbation sévèrede patient BPCO et une corrélation entre leur taux et le risque de décès du patient. La voiede signalisation du CXCR4 semble impliquée dans ce recrutement. La troisième étudecherche à explorer la localisation et les caractéristiques intra-pulmonaires des fibrocyteschez le patient BPCO à l’état stable. La quatrième étude a montré, in vivo, que le gallopamil,un inhibiteur calcique, pouvait diminuer la taille de muscle lisse bronchique de patientasthmatique sévère en ciblant la biogenèse mitochondriale. Ceci pourrait en faire une armethérapeutique interressante et totalement novatrice. La dernière étude a permis d’isoler unphénotype de patient asthmatique non sévère à « muscle lisse bronchique augmenté » quiprésente un risque accru d’exacerbation et de contrôle non optimal de leur asthme. Lesmitochondries semblent jouer un rôle clé comme dans l’asthme sévère. / Airway remodeling groups pathophysiological entities such as smooth musclehypertrophy in asthma or increase bronchial thickness due to infiltration of inflammatory cellsand fibrosis in COPD. These remodeling is correlated with the functional obstruction andtherefore with the severity of these diseases. The bronchial or lung biopsies analysis allowsto study this phenomenon which, after understanding, is an interesting therapeutic target.The first article is a review of indications of bronchoscopy in critically ill patients. The secondstudy showed an increase in blood fibrocytes during severe exacerbation of COPD patientand a correlation between their rate and the risk of patient death. CXCR4 signaling pathwayseems to be involved in the fibrocyte recruitment. The third study seeks to explore thelocation and characteristics of intra-pulmonary fibrocytes in stable COPD patients. The fourthstudy has shown, in vivo, that gallopamil, a calcium channel blocker, could reduce airwaysmooth muscle size in severe asthmatic patient by targeting mitochondrial biogenesis. Thiscould make it an interesting therapeutic weapon and totally innovative. The last study hasisolated a non-severe asthma phenotype with "increased bronchial smooth muscle," whichpresents an increased risk of exacerbation and a suboptimal control of their asthma. Themitochondria appear to play a key role as in severe asthma.

Abstract Reactive oxygen species (ROS) can cause severe damage to cells and organs but they are also important mediators of inflammatory responses and cellular signalling. Due to the significant role of ROS, the cells have evolved a broad antioxidative system to regulate the concentration of these species. Peroxiredoxins (Prxs) are enzymes that participate in the regulation of the cellular redox-homeostasis by detoxifying hydrogen peroxide. Prxs are not classified as conventional antioxidant enzymes and their physiological role, whether protective or regulatory, is still unclear. The aim of this project was to study the localization and regulation of Prxs in normal human lung and also their role in selected lung disorders (pulmonary sarcoidosis, pleural mesothelioma, lung carcinomas and chronic obstructive disorder, COPD). Additionally the expression of thioredoxin (Trx) and thioredoxin reductase (TrxR) was analysed in the lung of smokers and COPD patients. These enzymes are important reductants in cell and Prxs are one of their targets. Lung is an important organ in the field of ROS and antioxidant research since it is especially vulnerable to exogenous oxidative stress caused by pollutants, cigarette smoke and also by high oxygen pressure. The results showed that all six human Prxs were expressed in healthy human lung but in a cell-specific manner. The most prominent expression was detected in the epithelium and in macrophages, the cells most prone to oxidative stress. There were also differences in subcellular locations of Prxs. The expression of Prxs in non-malignant lung diseases (pulmonary sarcoidosis and COPD) and in smoker's lung was very similar with that in normal lung. Higher expression of Prx V and VI was detected in a subpopulation of macrophages sampled from COPD patients' lung. In contrast, Trx expression was induced in the bronchial epithelium of smoker's lung. Differences in the expression compared to normal lung were seen in lung malignancies (pleural mesothelioma and lung carcinomas). Interestingly, different Prxs were highly expressed in different types of carcinomas. In pleural mesothelioma, all Prxs except Prx IV were highly expressed when compared to normal pleura, in adenocarcinoma Prxs I, II, VI and especially IV, and in squamous cell carcinoma Prxs I, II and IV were upregulated. Tests performed on cultured cells in vitro revealed only a minor increase in the Prx expression after severe oxidant stress in malignant lung cell line originating from alveolar type II pneumocytes (A549) or non-malignant cell line derived from bronchial epithelium. None of the tested growth factors or cytokines affected Prx expression or oxidation state, but severe oxidant stress influenced remarkably the oxidation state of the Prxs.

Abstract Reactive nitrogen species (RNS) and reactive oxygen species (ROS) have been linked with the pathogenesis of lung malignancies and chronic obstructive pulmonary disease (COPD). In vitro studies indicated that mesothelioma and lung carcinoma cell lines synthesize nitric oxide synthases (NOS) mRNA. The Comet-assay indicated that asbestos fibers caused DNA single -strand breaks in mesothelial cells, and this effect was enhanced by glutathione depletion. The use of FPG in the Comet assay indicated that the asbestos induced DNA strand breaks were oxidant mediated. In vivo non-neoplastic pleura was mostly negative for inducible NOS (iNOS), while inflamed pleura was positive. The immunohistochemical expression of iNOS was detected in 74% and 96% of malignant mesotheliomas and metastatic pleural adenocarcinomas, respectively. Epithelial and mixed mesotheliomas expressed more often intense iNOS immunoreactivity compared to the sarcomatoid subtype. Normal mesothelial cells showed occasional positivity for endothelial NOS (eNOS), but reactive mesothelial cells were strongly stained. eNOS was found in 89% of mesotheliomas. Vascular endothelial growth factor (VEGF) was identified in 47%, a VEGF receptor FLK1 in 69% and the VEGF receptor, FLT1, in 71% of mesotheliomas. FLK1 or FLT1 immunoreactivities were more often seen in epithelioid and biphasic mesotheliomas than in sarcomatoid mesotheliomas. In lung samples of non-smokers, smokers and COPD patients, the levels of nitrotyrosine were higher in alveolar macrophages of smokers and COPD patients than in the non-smokers and in the alveolar epithelium of smokers and COPD patients than in the non-smokers. The iNOS expression was weak in the bronchial and alveolar epithelium in all groups but eNOS was most prominently expressed in alveolar macrophages while neuronal NOS (nNOS) was negative in all of the major cell types of the lung. Bronchial metaplasia-dysplasia-sequence was clearly positive for iNOS, nNOS and nitrotyrosine. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in metaplasia-dysplasia-lesions suggests a divergent role of NOSs in carcinogenesis and destruction of alveolar epithelium in emphysematous lung. In lung cancer samples, iNOS was detected in 40% cases, while 89% and 81% cases were positive for eNOS and nNOS, respectively. Intense eNOS staining was seen more often in adenocarcinomas than in squamous cells carcinomas, and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors. The patients with tumors showing high expression of iNOS, eNOS and nNOS, exhibited better survival, but this was not an independent prognostic factor.

Class of 2016 Abstract / Objectives: To assess the relationship between adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for the management of chronic obstructive pulmonary disease (COPD) exacerbations and the corresponding 30-day, all-cause readmissions rate in a community hospital. Methods: A retrospective chart review was conducted on patients admitted with the primary diagnosis of a COPD exacerbation. Medications administration records relevant to the GOLD guidelines were examined as separate independent variables in relation to a readmission within 30 days of discharge. Additional factors examined included: demographic data, resident of a long-term care facility, pre-index hospitalization, pulmonary consult, vaccines, length of stay (LOS), discharge medications, and follow-up appointments. Results: Electronic health records of 120 patients were reviewed and divided into non-readmitted patients (n = 65, mean age 73.4 ± 10.1 years), all-cause readmissions (n = 55, mean age 70.15 ± 9.69 years), and COPD-related readmissions (n = 21, mean age 70.7 ± 11.1 years). Patients with heart failure (p = 0.024), a LOS >5 days (p = 0.045), a pre-index hospitalization (p = 0.001), or who were long-term care residents (p = 0.024) experienced more all-cause readmissions. Females experienced less all-cause readmissions (p = 0.035). Significantly more patients with a pre-index hospitalization had a COPD-related readmission (p = 0.027). Lastly, adherence to the GOLD treatment parameters was not significantly different across all groups. Conclusions: COPD is a complex disease and adherence to the GOLD guidelines during an exacerbation is unlikely to significantly impact 30-day readmission rates.

Research on sex and gender in chronic obstructive pulmonary disease (COPD) has primarily focused on differences in pulmonary function. Detailed gender- and sex-based analyses of other aspects of COPD, including epidemiology, risk factors other than cigarette smoke, pathophysiology, and measurement tools are warranted. In Chapter Two we analyzed administrative health services data to compare the prevalence, mortality and use of drugs and spirometry in men and women with COPD. Contrary to recent predictions, we did not detect a dramatic increase in the prevalence or mortality of COPD over time in women compared to men. We discuss how different coding practices in medical billing can impact the results. In Chapter Three we examined sex differences in COPD phenotypes. We hypothesized that male smokers would have more emphysema whereas female smokers would have more airway wall remodeling using data from high resolution computed tomography (HRCT) scans. We did detect more emphysema in male smokers but there was no evidence of increased airway remodeling in women. We discuss the limits of HRCT to detect airway differences in women and men. In Chapter Four we examined the use of HRCT in assessing emphysema. We hypothesized that the computer-derived estimates of emphysema (the fractal value and the % low attenuation area (%LAA)) would differentiate COPD from non-COPD as accurately as the radiologist’s emphysema scores, and would provide similar predictions in both men and women. Instead, we found that the subjective rating of emphysema best differentiated COPD, and the fractal value (a measure of emphysematous lesion size) better differentiated COPD compared with an established objective measurement, the %LAA. These results were generally the same in men and women. In Chapter Five we examined characteristics of COPD in women exposed to biomass smoke. We hypothesized that biomass smoke would induce an airway disease-predominant phenotype. We found that women with biomass smoke-exposed COPD had greater airway remodeling and less emphysema than women with tobacco smoke-exposed COPD. In summary, these findings suggest that sex and gender differences are present in COPD epidemiology and pathophysiology. However, current research measurement tools may limit the ability to accurately measure these differences. / Graduate and Postdoctoral Studies / Graduate