This is a foundational study that applies Receiver Operating Characteristic (ROC) analysis to the evaluation of a chronic disease model that utilizes Remote Monitoring (RM) devices to identify clinical deterioration in a Chronic Obstructive Pulmonary Disease (COPD) population. Background: RM programmes in Disease Management (DM) are proliferating as one strategy to address management of chronic disease. The need to validate and quantify evidence-based value is acute. There is a need to apply new methods to better evaluate automated RM systems. ROC analysis is an engineering approach that has been widely applied to medical programmes but has not been applied to RM systems. Evaluation of classifiers, determination of thresholds and predictive accuracy for RM systems have not been evaluated using ROC analysis. Objectives: (1) apply ROC analysis to evaluation of a RM system; (2) analyse the performance of the model when applied to patient outcomes for a COPD population; (3) identify predictive classifier(s); (4) identify optimal threshold(s) and the predictive capacity of the classifiers. Methods: Parametric and non-parametric methods are utilized to determine accuracy, sensitivity, specificity and predictive capacity of classifiers Saturated Peripheral Oxygen (SpO2), Blood Pressure (BP), Pulse Rate (PR) based on event-based patient outcomes that include hospitalisation (IP), accident & emergency (A&E) and home visits (HH). Population: Patients identified with a primary diagnosis of COPD, monitored for a minimum of 183 days with at least one episode of in-patient (IP) hospitalisation for COPD in the 12 months preceding the monitoring period. Data Source: A subset of retrospective de-identified patient data from an NHS Direct evaluation of a COPD RM programme. Subsets utilized include classifiers, biometric readings, alerts generated by the system and resource utilisation. Contribution: Validates ROC methodology, identifies classifier performance and optimal threshold settings for the classifier, while making design recommendations and putting forth the next steps for research. The question answered by this research is that ROC analysis can provide additional information on the predictive capacity of RM systems. Justification of benefit: The results can be applied when evaluating health services and planning decisions on the costs and benefits. Methods can be applied to system design, protocol development, work flows and commissioning decisions based on value and benefit. Conclusion: Results validate the use of ROC analysis as a robust methodology for DM programmes that use RM devices to evaluate classifiers, thresholds and identification of the predictive capacity as well as identify areas where additional design may improve the predictive capacity of the model.

The problem of this study is to determine the vitamin B-6 status of patients who have chronic obstructive pulmonary disease (COPD). Erythrocyte aspartate transaminase assay was the method for measuring vitamin B-6 status. The vitamin B-6 status was examined in thirty subjects (ten COPD subjects and twenty control subjects). An unpaired t-test was used to compare the vitamin B-6 status of the COPD group versus the control group. Four determinants (percentage stimulation, ratio of basal to stimulated activity, basal activity, and stimulated activity) were used to determine vitamin B-6 status in both groups of subjects. Percentage stimulation and ratio of basal to stimulated activity were not significantly different (control group versus COPD group) at the .05 level. However, two of ten COPD subjects had values for percentage stimulation that were two standard deviations above the mean, indicating a poor B-6 status. In contrast, basal activity and stimulated activity of erythrocyte aspartate transaminase were found to be significantly lower at the .05 level in the COPD group than the control group. Therefore, the COPD subjects as a group had some biochemical characteristics of a lower level of vitamin B-6 than the controls.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) is a condition in which peripheral skeletal muscle undergoes myopathic changes which impair muscle function, limit physical performance, and can lead to significant disability. While the etiology of the dysfunction is unknown, this study was conducted to test the hypothesis that chronic hypoxemia leads to alterations in oxygen transport and muscle function. A primary objective was to validate elastase-induced emphysema in rats as an animal model of skeletal muscle dysfunction in COPD.Arterial blood gases were used to determine the severity of hypoxemia and sodium dodecyl sulfate- polyacrylamide gel electrophoresis was used to determine the proportions of myosin heavy chain isoforms I, IIa, IIx, and IIb. Measures of microvascular oxygenation and blood flow in the spinotrapezius muscle allowed for determination of both convective and diffusive oxygen supply to the muscle, as well as calculation of muscle oxygen consumption at rest and during electrically stimulated three-minute muscle contractions. Muscle performance measures included peak force, force-time integral, and fatigue index. Due to a presumed rat respiratory virus, which likely resulted in the control group being nearly as hypoxemic as the elastase-induced emphysema group, this study was not able to definitively test the hypothesis that chronic hypoxemia leads to both a diminished supply and demand of oxygen in skeletal muscle. Although many of the results of the present study were not statistically significant, they exhibited consistent trends over time and are likely of physiological significance. All measures of muscle performance were lower in the emphysema group. In addition, spinotrapezius muscle oxygen consumption and blood flow were lower in the emphysema group. The addition of supplemental oxygen during isolated, small-muscle mass exercise did increase the force-time integral by ~18% in both groups, suggesting that muscle work in these hypoxemic animals may be limited by oxygen supply. Thus, the data on muscle fiber type, oxygen consumption and muscle performance suggest that elastase-induced emphysema in rats leads to a similar skeletal muscle dysfunction that is observed in humans with COPD, and indicates that it is a valid animal model of skeletal muscle dysfunction in COPD.

Les mécanismes à l'origine de la Bronchopneumopathie Chronique Obstructive (BPCO) et de ses complications cardiovasculaires restent partiellement connus. Le NO est produit par les NO synthases en quantité importante dans le poumon des sujets emphysémateux, mais son rôle dans la maladie n'est pas connu. Une dysfonction endothéliale précoce liée à une diminution de la disponibilité en NO au niveau vasculaire a aussi été observée chez les patients BPCO. Dans un premier travail, nous avons montré que iNOS et eNOS étaient induites de manière diffuse dans le poumon de souris développant un emphysème après une instillation d'élastase. Le recours à des souris iNOS-/- et eNOS -/-, ainsi qu'à un inhibiteur pharmacologique d'iNOS (1400W) ont permis de montrer que l'induction d'iNOS dans le poumon était responsable d'une accumulation de protéines nitratées dans les pneumocytes de type 2 et d'une diminution de l'oxydation protéique. Cependant ni iNOS ni eNOS n'étaient nécessaires au développement de l'emphysème induit par l'élastase. Dans un deuxième travail, nous avons exploré l'effet de la polyglobulie, une complication de la BPCO hypoxique, sur la fonction endothéliale chez 15 patients polyglobuliques et 13 normoglobuliques atteints de BPCO de sévérité égale. La polyglobulie était associée de base à une viscosité sanguine plus élevée et un diamètre artérielbrachial plus important mais avec des forces de cisaillement calculées similaires. L'étude de la vasodilatation en réponse à l'hyperhémie et celle du flux sanguin de l'avant bras mesuré par plethysmographie d'occlusion veineuse en réponse à une perfusion d'acétylcholine (ACh), et de N-monomethyl-L-arginine (L-NMMA) ont permis de montrer que les artères systémiques despatients polyglobuliques ajustent leur diamètre aux forces de cisaillement aigues et chroniques de manière adaptée grâce à une libération adaptée de NO. De plus, nos résultats suggèrent que la polyglobulie modérée n'a pas d'effet délétère sur la fonctionvasculaire chez les patients BPCO. / The mechanisms that lead to COPD and cause its cardiovascular complications are partially known. NO is produced at high levels by NO-synthases in the human lung with emphysema, but its role in this disease is not clear. Interestingly, COPD patients have an endothelial dysfunction linked to the decrease of NO levels in peripheral blood vessels. In a first study, we demonstrated that iNOS and eNOS were diffusely upregulated in the lung of mice with emphysema after elastase instillation. By using iNOS-/- and eNOS -/- mice and a drug-based inhibitor of iNOS (1400W), we demonstrated that the induction of iNOS in the lung was responsible of an increase of protein nitration in alveolar type 2 cells and of an alleviated oxidation of proteins. However, neither iNOS nor eNOS were required for the development of elastase-induced inflammation and emphysema. In a second study, we evaluated the effectsof polycythemia, a common complication of hypoxic lung diseases, on the endothelial function in 15 polycythemic and 13 normocythemic patients with a COPD of equal severity. Polycythemia was associated with higher blood viscosity and a larger diameter of the brachial artery but with a similar calculated wall shear stress (WSS). We studied the flow-mediated brachial arteryvasodilation and the forearm blood-flow responses to endothelium- and non-endothelium-dependent N-monomethyl-L-arginine (LNMMA) infusion by plethysmography. We demonstrated that systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by an appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD.

Bakgrund: Malnutrition är vanligt hos patienter med kroniskt obstruktiv lungsjukdom (KOL). Malnutrition hos patienter med KOL kan orsaka nedsatt immunförsvar, ökad dyspné, minskad livskvalité samt att KOL-sjukdomen riskerar att öka i allvarlighetsgrad samt ha ett snabbare sjukdomsförlopp. År 2030 bedöms KOL vara den tredje vanligaste sjukdomen i världen. Därför är det viktigt som sjuksköterska att ha kunskap i vilka omvårdnadsåtgärder som kan användas vid malnutrition hos KOL-patienter. Syfte: Syftet med denna litteraturöversikt var att sammanställa KOL-patienters upplevda problem vid nutrition samt vilka omvårdnadsåtgärder sjuksköterskan kan vidta vid malnutrition. Metod: Litteraturöversikt baserad på 15 vetenskapliga artiklar. Resultat: Det fanns många olika problem som KOL-patienter upplevde i samband med nutrition. Dessa faktorer kunde vara både fysiska och psykiska. Sjuksköterskan kunde som omvårdnadsåtgärd upprätta kontakt med dietist för individuella råd och åtgärder till patienten. Som sjuksköterska var den stödjande samt kunskapsförmedlande rollen viktig, likväl att ge egenvårdsråd utifrån patientens önskemål samt förutsättningar. Slutsats: Den problematik som KOL-patienter upplevde i relation till nutrition var individuell. Nutrition hos KOL-patienter var ett komplext område då det innefattade både fysiska och psykiska bekymmer. Det är viktigt att sjuksköterskan arbetar personcentrerat vid vård av KOL-patienter då patienterna upplever olika problemområden i samband med nutrition, detta för att ge en god och säker vård. / Background: Malnutrition is common in patients with chronic obstructive pulmonary disease (COPD). Malnutrition in patients with COPD can cause impaired immune system, increased dyspnoea, decreased quality of life, and the COPD risk being increased in severity as well as having a faster disease course. In 2030, COPD is estimated to be the third most common disease in the world. Therefore, it is important as a nurse to have knowledge of which nurse care can be used in malnutrition in COPD patients. Aim: The aim of this literature review was to compile COPD patients' perceived problems with nutrition and what nurse care the nurse can take in malnutrition. Method: A literature review based on 15 scientific articles. Results: There were problems that occur for COPD patients that were caused according to their nutrition. These conditions could be both physical and psychological. The nurse could seek advice from a dietician to be informed of the best solution regarding nutritional needs of the patient. As a nurse it was important to pass on knowledge and give support to the patient whilst also advising on selfcare according to the patient's current condition and preferences. Conclusion: The variety of nutritional problems COPD patients face were highly individual and are therefore a complex subject as the effects are both physical and psychological. In general, the nurse should work closely with the patient as there can be nutrition related problems and in doing so, ensures appropriate and safe care.

The thesis begins with a theoretical part containing a general description of artificial pulmonary ventilation, invasive pulmonary ventilation and a detailed description of non-invasive pulmonary ventilation and chronic obstructive pulmonary disease. This section also focuses on a detailed description of non-invasive pulmonary ventilation in patients with chronic obstructive pulmonary disease. The aim of this thesis is to find out the real usability and success of non-invasive pulmonary ventilation in patients with chronic obstructive pulmonary disease received in 2018 at the department of ARO in the Hospital Jindřichův Hradec. The data was obtained from the patient documentation for 2018 from the ARO department and subsequently entered in the tables. The research found that in 2018, 162 patients had undergone the selected department, of whom 63 patients suffered from chronic obstructive pulmonary disease. Noninvasive pulmonary ventilation was used in 75 patients. Of the total number of non-invasive pulmonary ventilation applications, 30 were used in patients with chronic obstructive pulmonary disease. The success of non-invasive pulmonary ventilation in chronic patients reached 90 %. The main benefit is the fact that the number of patients with chronic obstructive pulmonary disease is increasing and that indeed chronic obstructive pulmonary disease is aggravated in the winter months. Another benefit is the finding that the success and true utility of non-invasive pulmonary ventilation in patients with chronic obstructive pulmonary disease is very good.

La BPCO (bronchopathie pulmonaire chronique obstructive) est un problème majeur de santé publique et représentera la 3ème cause de mortalité dans le monde en 2030. L’âge, le tabagisme, ainsi que la pollution atmosphérique via l’exposition aux particules de diesel mais également la pollution domestique – majoritairement représentée par la combustion domestique de biomasse – sont des facteurs de risque bien identifiés d’apparition d’une BPCO. Il n’existe à ce jour aucun traitement curatif pouvant interférer avec l’histoire naturelle de la maladie.Les cellules souches pluripotentes, et notamment les cellules souches humaines pluripotentes induites (hiPSCs), sont définies par deux propriétés fondamentales : l’auto-renouvellement et la capacité à se différencier en tous les types cellulaires de notre corps. Elles offrent une opportunité sans précédent de modéliser le développement humain normal et pathologique de l’appareil respiratoire.Ce projet de recherche a pour objectif de modéliser in vitro les trajectoires de la BPCO, en lien avec une origine développementale (racines pédiatriques) et/ou une susceptibilité au tabac. Afin d’élucider les mécanismes qui sous-tendent la pathogénie de la BPCO et de la susceptibilité au tabac, nous avons constitué deux groupes caricaturaux : i) 4 patients atteints d’une forme sévère de la BPCO, constituant le groupe « hautement susceptibles », ii) 4 patients fumeurs indemnes de BPCO ou tout autre comorbidité liée au tabac « hautement résistants » au tabac.Nous avons utilisés deux modèles de culture cellulaires in vitro : les hiPSCs et la culture de cellules épithéliales primaires bronchiques humaines (HBECs) cultivées en ALI (interface air liquide).Dans un premier temps, nous avons généré des lignées hiPSCs par reprogrammation cellulaire à partir du sang périphérique d’un sujet sain (contrôle), et de trois patients BPCO sévères hautement caractérisés. Dans un second temps, la différenciation dirigée des hiPSCs a permis de récapituler le développement pulmonaire précoce (génération de progéniteurs bronchiques NKX2.1) par la mise au point d’un protocole de différenciation dirigée robuste et reproductible sur plusieurs lignées hiPSCs. La maturation de ces progéniteurs bronchiques en culture 2D ou 3D a permis d’obtenir des structures épithéliales exprimant les marqueurs de cellules basales (KRT5), de cellules Club (CCSP), et ciliées (FOXJ1). Dans un second temps, ces épithélia seront exposés au tabac (CSE- cigarette smoke extract) afin d’induire un phénotype « BPCO-like ». Enfin, la culture des HBECs cultivées en ALI des patients BPCO sévères a été réalisée en condition exposée (CSE) et non exposée. La résistance transépithéliale, la motilité ciliaire, le profil sécrétoire et la diversité ARN ont été collecté.Ce travail a permis de mettre en place les outils nécessaires pour reproduire les trajectoires in vitro de la BPCO et élucider les origines de la pathologie. Les outils de séquençage à haut débit (transcriptomique dans notre étude), permettront de découvrir de nouveaux candidats, représentants de potentielles cibles en vue d’un criblage pharmacologique. / COPD (Chronic Obstructive Pulmonary Disease) is a major public health problem and will be the 3rd leading cause of death in the world in 2030. Age, smoking, and air pollution through the exposure to particulate matter but also domestic pollution - mostly represented by domestic biomass combustion - are well-identified risk factors for the development of COPD. To date, there is no cure that can interfere with the natural history of the disease.Pluripotent stem cells, including induced pluripotent human stem cells (hiPSCs), are defined by two fundamental properties: self-renewal and the ability to differentiate into all cell types in our body. They offer an unprecedented opportunity to model the normal and pathological human development of the respiratory system.This research project aimed to model in vitro the trajectories of COPD, related to a developmental origin (pediatric roots) and / or susceptibility to tobacco. In order to elucidate the underlying mechanisms of COPD and tobacco susceptibility, we established two extreme groups: i) 4 patients with a severe form of COPD, the "highly susceptible" group, ii) 4 patients who are free of COPD or other tobacco-related comorbidity despite heavy smoking, called as "highly resistant" to tobacco.We have used two different but complementary in vitro cell culture models: hiPSCs and human bronchial primary epithelial cell cultures (HBECs) grown in ALI condition (Air Liquid Interface).First of all, we generate hiPSCs cell lines by reprogramming cells from peripheral blood of a healthy subject (control), and three highly characterized severe COPD patients. In a second step, the directed differentiation of hiPSCs allowed to recapitulate the early pulmonary development (NKX2.1 generation of bronchial progenitors) by the development of a robust and reproducible directed differentiation protocol of several hiPSCs lines. The maturation of these bronchial progenitors in 2D or 3D culture allows the generation of epithelial structures expressing markers of KRT5 + basal cells , CSSP + Club cells and FOXJ1 + ciliated cells. In a second step, these epithelia will be exposed to tobacco (CSE-cigarette smoke extract) in order to induce a "COPD-like" phenotype. Finally, ALI culture of HBECs of severe COPD patients was performed in unexposed and exposed condition (CSE). Transepithelial resistance, ciliary motility, secretory profile, and RNA diversity were collected.This work allowed to put in place the necessary tools to reproduce the in vitro trajectories of COPD and to clarify the origins of this pathology. The high throughput sequencing tools (transcriptomic in our study), will allow the discovery of new candidates, that represent potential targets for future pharmacological screening.

O teste de exercício cardiopulmonar incremental (TECP) tem sido utilizado para avaliar o impacto global da doença em pacientes com DPOC. Considerando que as avaliações de exercício em laboratório são demoradas, caras e muitas vezes indisponíveis, o teste de caminhada de seis minutos (TC6min) não exige equipamentos caros e sofisticados, e pode ser facilmente realizado. Embora, a principal medida comumente utilizada no teste de caminhada seja a distância percorrida durante os 6 minutos (D), esta medida não leva em conta as diferenças de peso corpóreo, que podem influenciar o desempenho do exercício. Além disso, estudos anteriores correlacionaram o trabalho realizado durante o TC6min com TECP incremental pedalando, modalidade de exercício comumente associada a fadiga de quadríceps e menor consumo de oxigênio de pico ( O2) do que o TECP caminhando. O principal objetivo desse estudo foi avaliar a correlação entre a distância percorrida no TC6min (D) e o produto distância percorrida - peso corporal (DxP), uma estimativa do trabalho realizado durante o TC6min, com o O2 de pico obtido durante o TECP incremental em esteira ergométrica. Foram estudados trinta pacientes (19 homens), apresentando média (± DP) de idade de 66,3 ± 7,5 anos, com DPOC estável de moderada a grave intensidade (VEF1 médio de 1,1 ± 0,4L e 39 ± 13% predito) que realizaram TECP incremental em esteira ergométrica até o limite máximo de tolerância e o TC6min. Os testes foram realizados com pelo menos 48 horas de intervalo. A correlação de Pearson foi utilizada para avaliar o nível de associação entre o O2 pico, a distância e o trabalho executado durante o TC6min. Os pacientes percorreram 425,1 ± 78,6 m e realizaram um trabalho de 28166,4 ± 8368,4 Kg-m durante o TC6min, enquanto que o O2 de pico atingido foi 965,6 ± 370,1 mL/min (68,7 ± 17,4% do previsto) no TCPE. Ao final do exercício, em ambos os testes, a dispnéia foi a principal queixa e maior percepção de dispnéia e maior frequência cardíaca foi observado ao final do TECP comparativamente ao TC6min. O trabalho da caminhada (DxP) durante o TC6min demonstrou maior correlação com o O2 pico do que a distância (D) isoladamente. O mesmo ocorreu para VEF1, CVF, CI, DLCO, CO2, E e duplo produto (uma estimativa do trabalho do miocárdio), (r = 0,57; r = 0,57; r = 0,73; r = 0,7; r = 0,75; r = 0,65; r = 0,51; r = 0,4 respectivamente, todos com p <0,05). Dessa forma, esse estudo corrobora a melhor associação entre o trabalho estimado a partir da TC6min e o O2 pico atingido durante TECP, neste caso em esteira ergométrica, em comparação à distância isoladamente. / Incremental cardiopulmonary exercise testing (CPET) is increasingly used to evaluate the overall impact of the illness in patients with COPD. Whereas laboratory tests of exercise performance are often time-consuming, costly and frequently unavailable, the six-minute walk test (6MWT) does not require expensive or sophisticated equipments, and can be easily performed. Although, the main outcome measure commonly used in this field test is the distance walked during the predetermined 6 minutes (6MWD), this measure does not account for differences in body weight that are known to influence exercise performance. Furthermore, previous studies correlated the working performed during 6MWT with incremental cycling CPET, an exercise modality more associated with quadriceps fatigability and lower peak oxygen consumption ( O2) than incremental walking tests. The main objective of this study is to evaluate the correlation between 6MWD and its derivative walking distance-body weight product, an estimation of the work performed during 6MWT, with peak O2 obtained during a treadmill incremental CPET. The study enrolled thirty patients (19 males), with a mean (± SD) age of 66.3 ± 7.5 years and a stable moderate-to-severe COPD (ie, mean FEV1 1.1 ± 0.4L and 39 ± 13 % predicted) performed a ramp incremental CPET to the limit of tolerance on a treadmill and 6MWT. Tests were performed at least 48 h apart. Pearson´s correlation was used to assess the level of association between peak O2 and the distance and work executed during 6MWT. The patients walked 425.1 ± 78.6 m and performed a work of 28,166.4 ± 8368.4 (Kg-m) during the 6MWT while achieved a peak O2 of 965.6 ± 370.1 mL/min (68.7 ± 17.4% of predicted) in the treadmill CPET. They mainly stopped exercise due to dyspnea in both tests and reported a greater perception of dyspnea and higher heart rate was observed at the end of the CPET. The work of walking during the 6-MWT (DxW) provided greater and more frequent significant correlation with peak O2 than that observed with 6MWD.This was the case for FEV1, FVC, IC, DLCO, CO2, E, and double product (an estimate of myocardial work) (r=0.57; r=0.57; r=0.73; r=0.7; r=0.75; r=0.65; r=0.51 and r= 0.4, respectively; all p<0.05). This study provides evidence to corroborate the better association between the work estimated from the 6MWT and peak O2 achieved during CPET, in this case with a treadmill, than the 6MWD on isolation.

Made available in DSpace on 2016-08-19T18:16:09Z (GMT). No. of bitstreams: 1 Nilton Maciel.pdf: 552400 bytes, checksum: 57a80599a319d245747ee50f59ec8f25 (MD5) Previous issue date: 2007-07-16 / Introduction: The quality of life (QOL) of patients with Chronic Obstructive Pulmonary Disease (CPOD) is influenced by its impact on daily activities, due to the damage of the respiratory functional capacity. Objective: Correlate the QOL of women who carrying COPD with the respiratory functions and the 6 minutes walk test (6MWT). Methods: A cross study of 30 women with light or moderate COPD was carried out at the Pneumology Ambulatory care facility of the University Hospital, Presidente Dutra of the Maranhão State Federal University. The Saint George&#8217;s Respiratory Questionnaire (SGRQ) in the Respiratory Disease was used, to evaluate the measures of maximum respiratory pressures, spirometry and the 6MWT. Besides the descriptive statistics was realized the test t Student to dependent variables and the Linear Coefficient of Pearson for the correlation studies. Results: The QOL was altered in 96,7% of the studied patients in all sections of the SGRQ. The average distance (317,69 m) covered on the 6MWT, as well as the inspiratory muscular force (-53,48 cmH2O) and expiratory (69,55 cmH2O), were below the expected values for the normality. There was no correlation of the QOL with the BMI nor with the pulmonary function. The domains impact and the activities of the SGRQ presents negative correlation with age and positive with the Borg Scale. The domain impact still had correlation with the PImáx and the 6MWT. Conclusion: The patients with COPD of the study had presented a linear correlation among the QOL of the SGRQ and the variables of age, PImáx and the Borg Scale, still the low QOL in all the sections of the SGRQ, low performance on the 6MWT and reduced respiratory muscular force. / Introdução: A qualidade de vida (QV) de pacientes com Doença Pulmonar Obstrutiva Crônica (DPOC) é influenciada pelo impacto desta doença nas atividades da vida diária, decorrente do comprometimento da capacidade funcional respiratória. Objetivo: Correlacionar a QV de mulheres portadoras de DPOC com as funções respiratórias e o Teste de Caminha de Seis minutos (TC6). Método: Estudo transversal com 30 mulheres com DPOC leve ou moderada que estavam em tratamento no Ambulatório de Pneumologia do Hospital Universitário Presidente Dutra (APHUPD) da Universidade Federal do Maranhão (UFMA). Foi aplicado o questionário do Hospital Saint George na Doença Respiratória (SGRQ), realizado as medidas das pressões máximas respiratórias, a espirometria e, por último, o TC6. Além da estatística descritiva, foi realizado o teste t Student para variáveis dependentes e o Coeficiente Linear de Pearson para o estudo das correlações. Resultados: A QV esteve alterada em 96,7% das pacientes estudadas, tendo alterações em todos os domínios do SGRQ. Tanto a média da distância percorrida no TC6 (317,69 m) quanto à força muscular inspiratória (-53,48 cmH2O) e expiratória (69,55 cmH2O) ficaram abaixo dos valores de normalidade. Não houve correlação da QV com o IMC e nem com a função pulmonar. Os domínios impactos e atividades do SGRQ apresentaram correlação linear negativa com a idade e positiva com a escala de Borg. O domínio impacto teve ainda correlação com a PImáx e com o TC6. Conclusão: As pacientes com DPOC do estudo apresentaram correlação linear entre a QV do SGRQ e as variáveis de idade, PImáx, TC6 e escala de Borg, além de baixa QV em todos os domínios do SGRQ, baixo desempenho no TC6 e reduzida força muscular respiratória.

A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma das principais causas de mortalidade em todo mundo, apesar de ser prevenível e tratável. Resultante de uma resposta inflamatória anormal as partículas tóxicas inaladas, a DPOC caracterizada pela limitação progressiva do fluxo aéreo que é pouco responsiva a terapêutica farmacológica.Neste estudo caso-controle, envolvendo 51 portadores de DPOC e 51 controles, objetivou-se avaliar e quantificar danos e capacidade de reparação no DNA, bem como avaliar o papel de polimorfismos em genes de reparaçãona modulação deste. Foram determinados os níveis de danos no DNA, endógenos em sangue periféricos pelo ensaio cometa nas versões alcalina e neutra. Também foi determinado nível de danoinduzidos pelo agente alquilante metilmetano sulfonato (MMS), por 1 e 3 horas pós tratamentopelo ensaio cometa alcalino.Odano residual após 3h de tratamento com MMS foi calculado em relação à 1h (100% dano induzido), para cada sujeito. A peroxidação lipídica foi medida pela mensuração de espécies reativas de ácido tiobarbitúrico (TBARS) em plasma sanguíneo.Teste de micronúcleos de mucosa oral com análise de citoma (BMCyt) foi utilizado para detectar o dano citogenético. Ospolimorfismos em genes de reparação de DNA (XRCC1 Arg399Gln, OGG1 Ser326Cys, XRCC3 Thr241Met and XRCC4 Ile401Thr) foram identificados por PCR/RFLP.Os resultados do ensaio cometa revelaram que o dano basal no DNA em portadores de DPOC foi mais elevado, comparado aos controles, como mensurado pelo ensaio cometa alcalino e neutro. O dano residual, detectado pós-tratamento com MMS, foi maior nos portadores de DPOC, quando comparados aos controles. Os resultados demonstraram claramente uma relação entre os níveis de danos induzidos no DNA e os níveis de TBARSindicando alta suscetibilidade para dano alquilante e/ou inibição do reparo decorrente do estress oxidativo. Além disso, os pacientes apresentaram uma menor capacidade de reparação aos danos induzidos pelo MMS, quando comparados com os controles. Esta investigação ainda sugere um incremento do dano basal no DNA em portadores de DPOC, como analisado pelo ensaio cometa, nos sujeitos que possuem o alelo de risco dos polimorfismos genéticos XRCC1 (Arg399Gln) and XRCC3 (Thr241Met). O dano residual também foi mais elevado nos portadores de DPOC que possuíam o alelo de risco para os quatro genes estudados. Correlações negativas entre BMCyt (células binucleadas, broto nuclear, células com cromatina condensada e cariorrética) e função pulmonar foram observadas para os genótipos variantes.Os resultados do ensaio cometa e BMCyt estratificadospara a prática de exercício físico regular (EF-DPOC) ou não (DPOC)revelaram que o dano basal no DNA do grupo EF-DPOC foi maior que o observado nos grupos de DPOC e nos controles. O dano residual foi similar entre os grupos de EF-DPOC e controles, em contraste com o grupo DPOC que permaneceu elevado, indicando deficiência na reparação do DNA e morte celular precoce por apoptose das células danificadas. Os valores de TBARS foram menores no grupo EF-DPOCindicando resistência ao dano oxidativo. Em conclusão, portadores de DPOC apresentam elevado dano basal no DNA e são mais susceptíveis para danos exógenos no DNA, como o ocasionado pelo agente alquilante MMS. Esta susceptibilidade para dano exógeno, por correlacionar positivamente com o TBARS, sugere o envolvimento do estresse oxidativo na indução do dano e/ouinibição da reparação. A presença do genótipo variante XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met) e XRCC4 (Ile401Thr) modula o dano do DNA nos portadores de DPOC e incrementa o risco de desenvolvimento de câncer. O exercício físico frequente realizado pelos portadores de DPOCdiminuios níveis de peroxidação lipídica em plasma sanguíneo, a susceptibilidade para danos exógenos e a formação de anomalias celulares como broto nuclear e cromatina condensada. / Chronic Obstructive Pulmonary Disease (COPD) is a major cause of mortality worldwide, despite being preventable and treatable. Resulting from an abnormal inflammatory response to inhaled toxic particles, COPD is characterized by progressive airflow limitation which has poor responsiveness to pharmacological therapy. In this case-control study, involving 51 patients with COPD and 51 controls, we aimed to assess and to quantify DNA damage and repair capacity as well as the role of genetic polymorphisms in the modulation of DNA damage. Endogenous DNA damage levels were determined in peripheral blood by comet assay in alkaline and neutral versions. DNA damage-induced version with alkylating methylmethane sulfonate agent (MMS) was evaluated for 1 and 3 hours by comet assay in alkaline version. The residual damage after the 3-hour MMS treatment was calculated related to 1 hour (100% damage induced), for each subject. Lipid peroxidation was assessed by measuring thiobarbituric acid reactive species (TBARS) in blood plasma. The cytogenetic damage was evaluated by the buccal micronucleus cytome assay. The genetics polymorphisms in DNA repair genes (XRCC1 Arg399Gln, OGG1 Ser326Cys, XRCC3 Thr241Met and XRCC4Ile401Thr) were evaluated by PCR/RFLP respectively. The results of the comet assay showed that basal DNA damage in COPD patients was significantly higher compared to controls, as measured by the alkaline and neutral comet assay. The residual damage percentage, detected after the MMS treatment, increased in COPD patients than control group. The results clearly demonstrated a relationship between levels of DNA damage induced with higher levels of TBARS, indicating high susceptibility to alkylating damage and/ or repair inhibition resulting from oxidative stress. In addition, the patients showed a lower capacity to repair the damage induced by MMS, when compared with controls. This study suggests an increase in basal DNA damage in COPD patients, as analyzed by comet assay, in subjects having the risk allele of genetic polymorphisms XRCC1 (Arg399Gln) and XRCC3 (Thr241Met). The residual damage was higher in COPD patients who had the risk allele in the four genes analyzed. Negative correlations between BMCyt (binucleated, bud muclear, condensed chromatin and kariorrética cells) and pulmonary function were observed for COPD patients with genotype variants. The stratified results (comet assay and BMCyt) related to regular exercise practice (PE-COPD) or not (COPD) showed that basal DNA damage in the PE-COPD group was significantly higher than in the COPD and controls groups. Residual damage was similar between the controls and PE-COPD group; in contrast COPD residual damage remained high indicating deficiency in DNA repair and premature cell death by apoptosis of damaged cells. TBARS values were lower in PE-COPD indicating resistance to oxidative damage. In conclusion, COPD patients have higher basal DNA damage and are more susceptible to exogenous DNA damage, as caused by the alkylating agent MMS. This susceptibility to exogenous damage, being correlated positively with the TBARS, suggests the involvement of oxidative stress-induced damage and/or repair inhibition. This research suggests an increase in DNA damage in COPD patients with the risk allele of genetic polymorphisms XRCC1(Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met) and XRCC4 (Ile401Thr), analyzed by comet assay and BMCyt, and increased risk of developing cancer. Regular physical exercise performed by COPD patients significantly decreases lipid peroxidation in the blood plasma as well as susceptibility to exogenous damage and formation of cellular abnormalities, such as condensed chromatin and nuclear bud cells.