Introdução: A Síndrome Metabólica (MS) é uma comorbidade frequentemente encontrada nos pacientes que apresentam Doença Pulmonar Obstrutiva Crônica (DPOC). A DPOC e a MS possuem características em comum e o tabagismo é um fator de risco comum à DPOC e à MS. Apesar da intricada associação entre a DPOC e a MS, sabe-se muito pouco a respeito de como a co-ocorrência da MS afeta a resposta da DPOC ao treinamento físico - um tratamento efetivo para MS e que tem efeito protetor contra o enfisema induzido por tabaco - e à história natural desta. Objetivo: Avaliar como a ingestão crônica de frutose interfere na história natural e nos efeitos do treinamento físico aeróbio sobre a lesão pulmonar induzida por fumaça de cigarro. Métodos: Camundongos C57Bl/6 machos foram divididos em oito grupos (n=16-20/grupo): Controle, Fumo, Exercício, Fumo+Exercício, Frutose, Frutose+Fumo, Frutose+Exercício e Frutose+Fumo+Exercício; e expostos à fumaça de cigarro (30 minutos, 2x/dia), exercício físico (1 hora/dia) ou frutose (20% em água de beber) durante 12 semanas. Após o período de tratamento os animais foram anestesiados, submetidos à avaliação da mecânica respiratória e eutanasiados para coleta de sangue, lavado broncoalveolar (LBA), pulmões e músculos quadríceps para posteriores análises de histologia, dosagem de citocinas e avaliações de expressão gênica e estresse oxidativo. Resultados: A ingestão de frutose causou destruição do septo alveolar comparável com aquela causada pelo fumo (p < 0,001). A combinação de frutose e fumo produziu uma destruição alveolar mais severa do que qualquer um deles sozinho (p=0,008). O exercício físico inibiu o aumento do número total de células inflamatórias e macrófagos no LBA (p < 0,001), impediu o aumento dos níveis de interleucina (IL)-6, IL-10, IL-1beta, TNF-alfa, adiponectina e leptina no plasma e/ou músculo esquelético (p < 0,001), alterou a porcentagem de fibras colágenas e elásticas no parênquima pulmonar (p < 0,001) e atenuou o desenvolvimento do enfisema no grupo Frutose+Fumo+Exercício. Não houve efeito do exercício físico na mecânica respiratória, expressão de genes antioxidantes e estresse oxidativo. Conclusão: O treinamento físico aeróbio atenuou parcialmente o desenvolvimento do enfisema pulmonar em camundongos expostos à fumaça de cigarro e à frutose / Introduction: The Metabolic Syndrome (MS) is a comorbidity frequently presented by patients with Chronic Obstructive Pulmonary Disease (COPD). COPD shares with MS common features and tobacco use is a risk factor for both COPD and MS. Despite of this intricate association between COPD and MS, very little is known about how co-occurrence of MS might affect the response of COPD to physical exercise - an effective treatment for MS that has a protective effect against tobacco-induced COPD - and its natural history. Objective: To evaluate how chronic fructose intake interferes in the natural history and in the effects of aerobic exercise training on lung injury induced by exposure to CS. Methods: Male C57Bl/6 mice were assigned to 8 groups: Control, Smoke, Exercise, Smoke+Exercise, Fructose, Fructose+Smoke, Fructose+Exercise and Fructose+Smoke+Exercise (n=16-20/group) and treated accordingly with CS (30min twice/day), exercise training (1h/day) or fructose (20% in the drinking water) for 12 weeks. After the treatment period the animals were anesthetized, submitted to the evaluation of respiratory mechanics and were euthanized for collect of blood plasma, bronchoalveolar lavage fluid (BALF), lungs and quadriceps muscles for subsequent histology analysis and measures of cytokine levels, gene expression and oxidative stress. Results: Fructose ingestion caused destruction of alveolar septa comparable to that caused by the CS (p < 0,001). Combination of fructose and CS caused an alveolar destruction even more severe than either one alone (p=0,008). Exercise training inhibited the increase of the total number of inflammatory cells and macrophages in BALF (p < 0,001), inhibited the increase of the interleukin (IL)-6, IL-10, IL-1beta, TNF-alpha, adiponectin and leptin levels in plasma and/or skeletal muscle (p < 0,001), altered the percentage of collagen and elastic fibers in lung parenchyma (p < 0,001) and attenuated the development of emphysema in the Fructose+Smoke+Exercise group. There was no effect of exercise training on respiratory mechanics, antioxidant genes expression and oxidative stress. Conclusion: Aerobic exercise training partially attenuated the development of lung emphysema in mice exposed to cigarette smoke and fructose

CT is a powerful method for noninvasive assessment of the lung. Advancements to CT technology have guided the high-resolution structural and functional assessment of lung diseases. This has helped make the transition from characterizing the severity of lung disease to novel phenotyping of disease subtypes. Chronic obstructive pulmonary disease (COPD) is a spectrum of inflammatory lung disease affecting lung parenchyma, airways, and the pulmonary and systemic vasculature. Quantitative CT-based measures have largely focused on quantifying the extent of airway and parenchymal damage with disease. Recently perfusion CT method has been used to assess the pulmonary vascular bed. This technique was used to demonstrate a vascular etiology of smoking-associated centriacinar emphysema (CAE), a subtype of the COPD spectrum. However, technical challenges have limited the transition of this CT method to clinical studies to assess pulmonary vascular physiology. In this thesis, we introduce dual energy CT-perfused blood volume (DECT-PBV) as a novel image-based biomarker to assess peripheral pulmonary vascular dysfunction. Using this technique, we show that smoking-associated pulmonary perfusion heterogeneity, a marker of abnormal blood flow is a reversible process, in the midst of smoking-associated lung inflammation, and not a product of advanced lung disease. We demonstrate, via regional PBV measures and structural measures of the central pulmonary vessels, that the reversibility of pulmonary perfusion heterogeneity is a direct result of increased peripheral (downstream) parenchymal perfusion. We validate our quantitative imaging approach in a unique cohort of early CAE-susceptible smokers using a pharmaceutical intervention to dilate the pulmonary parenchymal vascular bed. The validated DECT approach and our novel DECT imaging findings extend our characterization of the vascular phenotype in inflammatory lung disease and provide a framework for future quantitative imaging studies of the lung to assess early intervention targeted to pulmonary vessels.

<p><font face="TimesNewRomanPSMT"> <p align="left">Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure.</p> </font></p>

<p>Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure. In this study pregnant rats have been divided into 4 groups: a group which received nicotine (1mg/kg body weight/day) subcutaneously, a group that received the tomato juice only (6mg/kg body weight/day per os), a third group that received the combination of tomato juice ( 6mg /kg body weight/ day per os) and nicotine (1mg/kg body weight /day subcutaneously ) . The control group that received saline (1mg/kg body weight /day) subcutaneously and water. The injections were done during pregnancy and lactation until weaning at postnatal day 21. The results showed that maternal nicotine exposure during gestation and lactation leads to a gradual damage of the lung parenchyma and slower formation of the alveoli during the equilibrated phase of the lung growth leading to a decrease in the internal surface area required for gas exchange. Supplementation with tomato juice during gestation and lactation prevents all the adverse effects of maternal nicotine exposure on the lungs of the offspring. Since nicotine induce an increase in the oxidant levels of the mother and the fetus, my results imply that lycopene protected the lungs of the offsprings against the oxidants and thus against changes in the program that controls lung development as the animals age. This is supported by the observation that at postnatal day 84 the antioxidant.</p>

<p>Tobacco smoking during pregnancy and lactation is a common habit and accounts for a significant percentage of fetal morbidity and mortality worldwide. The offspring is as a result exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include / intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating&nbsp / the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring / to establish whether tomato juice can have protective effects on the fetal lung&nbsp / development and function in the offspring / and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during&nbsp / gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of&nbsp / the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung&nbsp / parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was&nbsp / accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of&nbsp / remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in&nbsp / senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature&nbsp / aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long&nbsp / after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces&nbsp / the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age&nbsp / prematurely. The supplementation of the mother&rsquo / s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring&nbsp / against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother&rsquo / s diet with tomato juice prevented&nbsp / the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation.&nbsp / </p>

Purpose/Aims: The American Thoracic Society (ATS) published recommendations for alpha-1 antitrypsin deficiency (AATD) testing in 2003. This descriptive project evaluates the outcomes of ATS AATD guideline use in the setting of the pulmonary function testing (PFT) lab.The specific aims met by this descriptive project describe the prevalence of AATD cases and carriers in the sample, examine to what degree the established clinical guideline promoted accurate patient selection for the alpha-1 test in the sample, and aimed to determine whether alpha-1 antitrypsin blood levels are reduced in current smokers compared to former or never smokers.Background: Alpha-1 antitrypsin prevents lung tissue breakdown by attenuating excess elastase released from neutrophils during the inflammatory response. Smoking impairs alpha-1 antitrypsin protection at the site of lung inflammation promoting emphysema development. In the case of genetic mutation, protective alpha-1 antitrypsin levels are reduced, causing emphysema even in non-smokers. Significantly reduced protective levels of alpha-1 antitrypsin increase the odds for morbidity and early mortality from emphysema. The literature provides support for targeted testing in the population most affected.Sample/Methods: The sample population included adults 21 through 79 years completing pulmonary function testing over 18 months in a metropolitan pulmonary medicine practice and was retrospectively reviewed.Of the 521 in the sample, 190 were tested for AATD, and 24 were found to carry an abnormal genotype. However, using Table 11 from the ATS CPG failed to provide structured, consistent guidance in selecting patients for AATD testing. Still, the prevalence of the abnormal genotypes MS, MZ, SZ, and ZZ was increased in this pulmonary population compared to the published estimated prevalence for the general population.A structured decision-tree, developed from the original guideline for diagnostic testing, may provide superior guidance for AATD test patient selection in this setting. Increased case finding by targeted testing of patients in the setting of the pulmonary function lab can serve to integrate this clinical practice guideline in a consistent streamlined fashion.In this sample, no difference between AAT blood levels among ever, never, and current tobacco smokers was detected. A more powerful sample is needed.

<p><font face="TimesNewRomanPSMT"> <p align="left">Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure.</p> </font></p>

<p>Nicotine exposure to the fetus through tobacco smoking or nicotine replacement therapy during the whole period of gestation and lactation causes diverse effects on fetal and neonatal lung development, integrity and maturation which compromise the gas exchange function of the lungs and renders this vital organ susceptible to gradual damage and different diseases in latter life. Maternal nicotine exposure during gestation and lactation results in gradual destruction of the lung parenchyma, and this leads to the combination of many small air sacs in one bigger alveoli which is a sign of emphysema. Many researchers speculated that the way in which, nicotine causes emphysema and other damage, is by inducing the formation of many reactive oxygen species (ROS), and creating an imbalance between the oxidants and the antioxidants of the body, which is termed oxidative stress. The aim of this study was to assess the effects of nicotine exposure on the lung of the fetal and neonate rat during gestation and lactation as gas exchanger, and also to see whether the supplementation of tomato juice containing lycopene, a powerful carotenoid antioxidant could protect the lungs against these effects of maternal nicotine exposure. In this study pregnant rats have been divided into 4 groups: a group which received nicotine (1mg/kg body weight/day) subcutaneously, a group that received the tomato juice only (6mg/kg body weight/day per os), a third group that received the combination of tomato juice ( 6mg /kg body weight/ day per os) and nicotine (1mg/kg body weight /day subcutaneously ) . The control group that received saline (1mg/kg body weight /day) subcutaneously and water. The injections were done during pregnancy and lactation until weaning at postnatal day 21. The results showed that maternal nicotine exposure during gestation and lactation leads to a gradual damage of the lung parenchyma and slower formation of the alveoli during the equilibrated phase of the lung growth leading to a decrease in the internal surface area required for gas exchange. Supplementation with tomato juice during gestation and lactation prevents all the adverse effects of maternal nicotine exposure on the lungs of the offspring. Since nicotine induce an increase in the oxidant levels of the mother and the fetus, my results imply that lycopene protected the lungs of the offsprings against the oxidants and thus against changes in the program that controls lung development as the animals age. This is supported by the observation that at postnatal day 84 the antioxidant.</p>

<p>Tobacco smoking during pregnancy and lactation is a common habit and accounts for a significant percentage of fetal morbidity and mortality worldwide. The offspring is as a result exposed to nicotine through the blood and the milk of the mother. Nicotine is thus expected to interact with the developing fetus and the offspring of mothers who smoke or use NRT for smoking cessation, resulting in the interference with normal fetal and neonatal lung development. Maternal cigarette smoke or nicotine exposure produces adverse effects in the lungs of offspring, these include / intrauterine growth retardation, low birth weight, premature birth, reduced pulmonary function at birth, and a high occurrence of respiratory illnesses after birth. This study aimed at investigating&nbsp / the effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring / to establish whether tomato juice can have protective effects on the fetal lung&nbsp / development and function in the offspring / and to determine if nicotine cases premature aging of the lungs of the offspring. It was therefore shown that maternal exposure to nicotine during&nbsp / gestation and lactation ad no significant effect on the growth parameters of the offspring. Maternal nicotine exposure during gestation and lactation had no effect on the growth parameters of&nbsp / the offspring, but resulted in compromised lung structure and function. The morphometric results demonstrated decrease in alveolar number, increase in alveolar size, and decrease in lung&nbsp / parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was&nbsp / accompanied by an increase in alveolar size (Lm), and a decrease in the tissue volume of the lung parenchyma. Thickening of alveolar walls was also evident and serves as an indication of&nbsp / remodeling of the extracellular matrix, also a characteristic of emphysema. A consequence of the gradual deterioration of the lung parenchyma is a decrease in the alveolar surface area available for gas exchange. The present study showed that the emphysematous lesions were conceivably a result of a reduced rate of cell proliferation accompanied by the increase in&nbsp / senescent cells numbers in the alveolar walls of the exposed offspring. The data of this study suggests that maternal nicotine exposure during gestation and lactation induces premature&nbsp / aging of the lungs of the offspring rendering the lungs of the offspring more susceptible to disease later in life. Since these structural changes occurred later in the life of the offspring and long&nbsp / after nicotine withdrawal, it is suggested that it is programmed during gestation and lactation. Smoking and NRT result in an increased load of oxidants in the mother and fetus. It also reduces&nbsp / the level of anti-oxidants and thereby compromising the ability of the mother to protect the fetus. It is hypothesized that this oxidant-antioxidant imbalance will program the lungs to age&nbsp / prematurely. The supplementation of the mother&rsquo / s diet with tomato juice, rich in lycopene, other anti-oxidants such as vitamin C, as well as phytonutrients protected the lungs of the offspring&nbsp / against the adverse effects of maternal nicotine exposure. This supports the hypothesis mentioned above. The study further showed that the effects of grand-maternal nicotine exposure during gestation and lactation on the lungs of the F1 offspring is also transferred to the F2 offspring. This is most likely via the paternal and maternal germ line. Since tomato juice supplementation of the mother&rsquo / s diet with tomato juice prevented&nbsp / the adverse effects of maternal nicotine exposure on the lungs of the offspring, it is conceivable that it will prevent transfer of these changes to the F2 generation.&nbsp / </p>

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.