Philosophiae Doctor - PhD / 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 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 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 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 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 parenchyma of the nicotine exposed animals showing a gradual deterioration of the lung parenchyma. Structural alterations include emphysematous lesions, where the latter was 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 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 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 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 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 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 prematurely. The supplementation of the mother’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 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’s diet with tomato juice prevented 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. / South Africa

The association between cigarette smoking and the risk of cardiovascular diseases (CVD) is well established. However, the effect of other, less common, types of smoking on CVD risk, such as pipes and cigars in developed countries, remains uncertain. By contrast, in developing countries, a large panel of smokeless tobacco products are consumed alongside smoking products, with unknown effects on the risk of CVD. The aim of this thesis is to investigate the association between various forms of tobacco use with the risk of CVD in the setting of developed countries and of a developing country with a large population, Pakistan.

Magister Chirurgiae Dentium (MChD) / Water-pipe tobacco smoking (WTS) is a form of tobacco use with different names. There is a misconception that passing tobacco smoke through water reduces its harmful effects to increase its popularity. One million individuals smoke water-pipe daily, resulting in approximately five million deaths per annum globally. The toxic effects of WTS are related to the several components of the tobacco mixture. WTS contains 100 times more tar, four-fold more nicotine, eleven-fold more Carbon Monoxide (CO), and two to five-fold more polycyclic aromatic hydrocarbons than cigarettes.

L'endothélium artériel pulmonaire joue un rôle déterminant dans la régulation du tonus vasomoteur en libérant des substances vasodilatatrices et vasoconstrictrices. Toute perturbation des fonctions endothéliales entraîne une perte de l'équilibre physiologique très finement régulé entre réponse vasoconstrictrice et vasodilatatrice, avec perte conjointe du contrôle de la prolifération des cellules musculaires lisses vasculaires et de l'effet antiagrégant plaquettaire. Ces modifications conduisent à un remodelage du lit vasculaire pulmonaire avec une augmentation des résistances vasculaires parfois à l'origine d'une hypertension pulmonaire (HTP) irréversible. Le rôle de l'hypoxémie n'y est pas exclusif. Le réseau bronchique est soumis quant à lui à des agressions physiques par les particules inhalées. Celles-ci peuvent entraîner un remodelage bronchique et une perturbation du tonus bronchique et de la broncho-réactivité, dont les médiateurs peuvent être en partie partagés par la dysfonction vasculaire.Le but de ce travail était d'évaluer dans un premier temps l'existence d'une dysfonction endothéliale, en tant que précurseur potentiel d'une HTP, dans deux modèles de bronchopathies chroniques à des stades opposés de la sévérité de l'atteinte respiratoire : la mucoviscidose terminale et le tabagisme avec peu ou pas d'impact sur la fonction respiratoire.Nous avons ainsi montré à partir d'explants pulmonaires qu'une dysfonction endothéliale était fréquente au cours de la mucoviscidose au stade pré-greffe et qu'elle était au-moins en partie liée à une surexpression vasculaire pulmonaire de l'ET-1 et de ses récepteurs ET-A.Nous avons montré par ailleurs que 25% environ des sujets fumeurs à fonction respiratoire normale ou peu altérée présentaient également une telle dysfonction. Nous en avons étudié ici deux voies physiopathologiques potentielles, celle de l'ET-1 et celle qui gouverne la synthèse du NO : la balance NO Synthases (NOS)/arginases. Nous avons mis en évidence une surexpression des récepteurs ET-A de l'ET-1 chez les sujets avec dysfonction ainsi qu'une corrélation inverse entre cette expression et la réponse vasoactive à l'Acétylcholine (Ach). Par ailleurs, si le NO a entre autres un effet anti-prolifératif sur les cellules musculaires lisses, la voie des arginases - système enzymatique compétitif avec les NOS - mène quant à elle à la réparation et au remodelage. Nous avons étudié l'expression vasculaire de ces différentes enzymes ainsi que l'effet pharmacologique d'inhibiteurs des NOS ou des arginases sur la réponse vasoactive à l'Ach. Nous avons montré qu'il n'existait pas de déficit d'expression des NOS et qu'il ne semblait pas y avoir d'effet délétère des arginases dans la dysfonction endothéliale dans ce modèle.Parallèlement aux mécanismes sous-tendant le remodelage vasculaire au cours du tabagisme nous avons recherché l'existence d'une « dysfonction » bronchique chez ces fumeurs, qui pourrait précéder le remodelage bronchique qui les caractérise. La présence d'une hyperréactivité bronchique est un marqueur prédictif de remodelage des voies aériennes et de l'obstruction bronchique qui en découle. Le rôle de la balance NOS/arginases dans le contrôle du tonus bronchique est encore méconnu. Notre premier objectif était d'évaluer l'expression de cette balance enzymatique dans le tissu bronchique de ces patients et le second d'étudier les effets de l'inhibition des NOS et des arginases sur la réponse bronchoconstrictrice à l'Ach. Nous avons montré qu'une augmentation d'expression bronchique de la NOS 2 chez les fumeurs était impliquée dans la régulation du tonus bronchique et dans l'obstruction bronchique, tandis qu'une augmentation de l'activité des arginases était impliquée dans la sensibilité bronchique. / Pulmonary arteriel endothelium has a key role in the regulation of vascular tone by the release of dilating and constrictive mediators. Impairment of endothlium functions leads to a loss of the physiological equilibrium between vasoconstriction and vasodilation, together with the loss of vascular smooth muscle cells (SMC) proliferation. These alterations induce pulmonary vascular remodeling and elevation of vascular resistance which can lead to an irreversible pulmonary hypertension (PH). The role of hypoxemia is not exclusive. Airways are exposed to physical aggressions by inhaled particles, which can lead to bronchial remodeling and impaired bronchial tone and reactivity, the mediators of which can be partly shared by endothelial dysfunction.Our goal was to evaluate the existence of endothelial dysfunction as a precursor of PH in 2 models of chronic bronchopathy of opposite stages of disease severity: end-stage cystic fibrosis (CF) and tobacco smoking with or without impaired lung function. We showed that in end-stage CF pulmonary explants, endothelial dysfunction is frequent and that it was at least partly due to a vascular upregulation of the endothelin (ET)-1 pathway.Furthermore, approximately ¼ of smokers with normal or poorly impaired lung function also displayed a similar endothelial dysfunction. We studied therein 2 potential physiopathological pathways, that of ET-1 and that which governs nitric oxide (NO) synthesis: the NO synthases (NOS)/arginases balance. We showed an upregulation of ET-A receptor expression and an inverse correlation between this expression and the vasoactive response to acetylcholine (Ach). If NO has an anti mitogenic effect on SMC, the arginases pathway-competitive with the NOS- leads to tissue repair and remodeling.We studied the vascular expression of these enzymes and the pharmacological effect of NOS and arginases inhibitors on response to Ach. We showed that the expression of NOS was not deficient and that arginases did not seem to have a deleterious effect on endothelial function in this model.Concomitantly to these mechanisms leading to vascular remodeling, wr searched for a bronchial dysfunction in smokers which could antecede bronchial remodeling, a well known feature of tobacco smoking. Bronchial hyperresponsiveness is a predictive marker of airway remodeling and subsequent bronchial obstruction. The role of the NOS/arginases pathway in the control of bronchial tone is still unknown. We evaluated the bronchial expression of the NOS/arginases balance in smokers and the effects of NOS and arginases inhibitors on bronchoconstrictive response to Ach. We found that an upregulation of NOS2 expression in COPD patients is involved in airway tone regulation and functional airflow limitation, whereas increased arginase activity is involved in airway sensitivity.

Magister Psychologiae - MPsych / Tobacco smoking is the second major cause of preventable deaths in South Africa. The Western Cape has the second highest smoking rates in South Africa and the highest smoking rate among young women. Previous studies indicate that female smokers are more vulnerable to the harmful effects of smoking than males. The aim of this study was to investigate the knowledge, attitudes and beliefs regarding health risks of tobacco use among female undergraduate students at the University of the Western Cape. A sample of 210 female psychology 1 students were recruited and served as research participants. Data was collected using a self-administered questionnaire adapted from instruments measuring knowledge, attitudes and beliefs regarding the health risks of tobacco smoking. Descriptive and Inferential statistics were used to analyse the data. The Health Belief Model was used as the theoretical framework for this study. The results showed a 20% prevalence of smoking among the students. Differences were found among smoking and non-smoking participants regarding their knowledge, attitudes and beliefs about the health risks of tobacco smoking. The results of the study may inform smoking prevention and intervention strategies aimed at female students on campus.

Nicotine was not included in previous efforts to identify the most important toxicants of tobacco smoke. A health risk assessment of nicotine for smokers of cigarettes was conducted using the margin of exposure (MOE) approach and results were compared to literature MOEs of various other tobacco toxicants. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Dose-response modelling of human and animal data was used to derive the benchmark dose. The MOE was calculated using probabilistic Monte Carlo simulations for daily cigarette smokers. Benchmark dose values ranged from 0.004 mg/kg bodyweight for symptoms of intoxication in children to 3 mg/kg bodyweight for mortality in animals; MOEs ranged from below 1 up to 7.6 indicating a considerable consumer risk. The dimension of the MOEs is similar to those of other tobacco toxicants with high concerns relating to adverse health effects such as acrolein or formaldehyde. Owing to the lack of toxicological data in particular relating to cancer, long term animal testing studies for nicotine are urgently necessary. There is immediate need of action concerning the risk of nicotine also with regard to electronic cigarettes and smokeless tobacco.

would like to thank my thesis supervisor, Dr Devendra Amre, for his guidance. I would also like to extend my gratitude to the CHU Ste-Justine Research Center and the Ste-Justine Foundation, as well as the Department of Biomedical Sciences of the University of Montreal, for their generous support. / L'importance des déterminants génétiques de la maladie de Crohn (MC) chez l'enfant est bien connue, mais nos connaissances sur la contribution des facteurs de risque environnementaux demeurent limitées. Parmi les facteurs de risque du déclenchement de la MC chez l'adulte, figure le tabac. Le lien entre le tabagisme actif et le déclenchement de la MC a été maintes fois démontré. Cependant, les études menées jusqu'à présent sur l'influence de la fumée secondaire sur le déclenchement de la MC chez l'enfant ne sont pas consistantes, et ont souvent montré des résultats contradictoires. Le principal objectif de notre étude était donc de déterminer l'influence de l'exposition à la fumée secondaire pendant la grossesse et durant l'enfance sur le déclenchement de la MC chez l'enfant. Méthodes: Nous avons mené une étude cas-témoins auprès d'enfants caucasiens. Les cas avaient reçu un diagnostic de MC avant l'âge de 20 ans à la clinique de gastroentérologie pédiatrique du CHU-Sainte-Justine de Montréal (n=132), et les témoins (n=131) ont été sélectionnés parmi les patients du service de gastroentérologie ou d'orthopédie du même hôpital, sans histoire de maladie chronique intestinale. Nous avons apparié les cas et les témoins selon le moment du diagnostic (± 3 mois) et leur lieu de résidence (à l'aide du code postal). L'information sur l'exposition à la fumée secondaire au cours de la grossesse et durant l'enfance, ainsi que les autres facteurs de risque ont été colligés à l'aide d'un questionnaire. L'analyse des déterminants du déclenchement de la MC a été faite par régression logistique pour estimer le ratio de cote (RC) ainsi que les intervalles de confiance correspondant (IC95%). Résultats: L'âge moyen (± ET) des cas était légèrement plus élevé que celui des témoins (12,7 ± 4,0 vs. 11,4 ± 4,7; p=0,01). Le sexe était réparti de manière égale entre les groupes. L’histoire familiale s'est avérée significativement associée à la MC (p=0,01). La régression logistique multivariée n'a montré aucun lien statistiquement significatif entre le tabagisme de la mère pendant la grossesse et la MC, en comparant les mères qui ont fumé pendant la grossesse avec celles qui n’ont fumé ni pendant la / positively associated with the disease. In children, there is interest in understanding whether passive exposure to environmental tobacco smoke (ETS) could confer similar risks. However, current studies have provided inconsistent results. The major objective of our study was thus to comprehensively ascertain whether ETS exposure during pregnancy and childhood was associated with the risk of developing CD in children. Methods: We carried out a case-control study based on Caucasian children diagnosed with CD (n=132) prior to age 20 at a pediatric gastroenterology clinic in Montreal (CHU-Sainte-Justine). Controls (n=131) were children having visited the orthopedic or gastroenterology clinics, who did not have a past/current history of IBD, were diagnosed within ± 3 months of case diagnosis and resided in the same geographic area (based on the first 3 digits of the postal code) as the cases. Information on ETS during and post-pregnancy and other potential risk factors for CD was acquired using a structured questionnaire. Associations between ETS and CD were analyzed using unconditional logistic regression. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated. Results: The mean age (±SD) of the cases 12.7 (±4.0) was slightly higher than the controls (11.4±4.7) (p-value=0.01). Gender was equally distributed between the groups. Family history was positively associated with CD (p-value=0.01). Multivariate logistic regression did not reveal any association with CD when mothers who smoked during pregnancy were compared to those who neither smoked during pregnancy nor post-pregnancy (OR=1.55, 95% CI=0.84-2.86). Paternal smoking during pregnancy was also not associated with risk of CD (OR=0.95, 95% CI=0.33-2.75). Exposure of ETS to the child during childhood via maternal smoking appeared to increase risk (OR=3.54, 95% CI=0.71-17.57) but the risks were not iv significant. Paternal smoking during childhood also appeared to enhance risk of CD, in particular when the parents also smoked during pregnancy (OR=2.52, 95% CI=1.11-5.72). Conclusions: ETS exposure per se during pregnancy does not seem to confer risks of CD in children. However, ETS exposure during childhood either from maternal or paternal smoking appears to contribute to risk of CD in the child. Further studies are required to validate these associations.

This thesis is aimed at tabacism problems encountered by 9th grade elementary school pupils in the area of Most (Czech Republic). Comparison of gender aspect is accented. The primary target was to figure out the age of first experience with tobacco smoking and to investigate the subjective reasons leading to this act. The other domain of investigation was the attitude of adolescents to tobacco attractiveness and their tolerance to smoking of their future life partners. The thesis also compares my investigation results to studies related to the influence of smoking parents on their children's early experience with tobacco, and related to the manner in which are the elementary school children informed about tabacism issues. Some results of investigation are compared with existing research in the comments. The following facts were discovered - Adolescent girls smoke more than boys, and smoking parents have substantial influence on their children. The majority of children with smoking parents has more experience with tabacism than the children of non-smokers. The primary prevention in schools is performed as part of health education lessons, or similar subjects' lessons. The most usual way in which the children receive information about tabacism is speech and lecture. It was figured out, tabacism...

OF THE THESIS Name: Mgr. Markéta Šídová Specialization: Adiktologie Head of the thesis: Mgr. Lenka Šťastná, Ph.D. Pages: 145 The name of thesis: Tobacco smoking and motivation to change in relation to pregnancy Abstract: Background: The pregnancy gives the smoking women the opportunity to change their attitude to smoking tobacco. In the Czech Republic is still missing a study describing the motivation to change smoking specifically in connection with pregnancy. Goals: Describe the basic motivation to stop smoking by pregnant women. Methods: Quantitative survey. The questionnaire consists of four sections (anamnesis, gathering information about smoking during pregnancy, motivation to change smoking behaviour, Fagerström Test of Nicotine Dependence). Motivation section is inspired by Reasons for Quiting Scale (RFQ). Evaluation using the descriptive statistics and non-parametric statistical tests. File: The study analyses two sets of pregnant women - electronic (collection via web form, N = 96) and clinical (collection from the Department of Gynaecology and Obstetrics, 1st Faculty of Medicine and VFN, N = 40). The files are divided into 4 subgroups according to the current smoking behaviour. Results: Most women in both groups do not smoke and have never smoked or stopped in connection with pregnancy....

Introdução: O tabagismo é um problema crônico e de enfrentamento complexo. A ampliação da legislação, a conscientização da sociedade e a menor aceitação social do tabagismo, aumentaram a procura por serviços de cessação do tabagismo. A avaliação de programas desse tipo é tarefa complexa, considerando os diferentes níveis de intervenção, a diversidade de cenários e atores envolvidos. A avaliação de programas de cessação do tabagismo necessita incorporar ferramentas participativas, capazes de apontar a eficiência do programa, além de fomentar ações de transformação das práticas. Esta pesquisa buscou configurar uma matriz avaliativa capaz de contribuir na organização e autoaprendizagem de serviços dirigidos aos sujeitos em suas tentativas de parar de fumar, captando os diferentes contextos presentes na intervenção, nos cenários e nos atores. As questões da pesquisa foram: Quais são os indicadores que podem apontar o quanto um serviço se aproxima ou se distancia das práticas baseadas em evidências e dos modelos e diretrizes da promoção da saúde? Quais são os elementos que indicam ou não a qualidade de um serviço de tratamento do tabagismo? Objetivos: Desenvolver a matriz de indicadores de um serviço de tratamento do tabagismo. Para tanto buscou-se a) Identificar a percepção de experts, usuários e profissionais sobre serviços de tratamento do tabagismo; b) Caracterizar as práticas e bases de um serviço de cessação do tabagismo; c) Construir o modelo lógico avaliativo desse serviço; c) Formular as bases teóricas e práticas para a construção de matriz avaliativa de indicadores para um serviço de tratamento do tabagismo. Método: Situado no desenho orientado por modelo teórico (theory-driven evaluation) na perspectiva da Promoção da Saúde preconizada por Hartz, o percurso metodológico foi apoiado nas abordagens qualitativas e participativas e na estratégia da pesquisa-ação. O cenário de estudo foi o serviço de cessação do tabagismo de um hospital universitário, no município de São Paulo. Foram sujeitos dessa pesquisa profissionais de referência para o PNCT (experts), profissionais que atuam diretamente no serviço (implicados) e usuários do serviço. A análise e discussão dos achados apoiaram-se na triangulação de dados, correlacionada com a literatura. Resultados: O desfecho desta pesquisa foi o desenvolvimento da matriz avaliativa. Utilizou-se as percepções dos experts, implicados e usuários sobre as dimensões de estrutura, processo e resultado. A legislação, o financiamento, extensão e cobertura, a acessibilidade, as instalações, os recursos humanos, os equipamentos e insumos foram apontados como categorias para estrutura. Na dimensão processo as categorias foram: divulgação e captação, acolhimento e busca ativa, o perfil sócio psicológico dos usuários, a rede de referência e contra referência, o diagnóstico, acompanhamento e as estratégias educativas com base no autocuidado e na redução de danos. No âmbito de resultados os sujeitos pontuaram: a taxa de sucesso na cessação do tabagismo, a regularidade do serviço, a adesão, o respeito à autonomia, a melhora na qualidade de vida e a satisfação do usuário. Conclusão: Conclui-se que a matriz avaliativa construída possui potencial para avaliar a qualidade do serviço e promover o aprendizado institucional e o desenvolvimento pessoal/profissional. Contribui para o movimento de reflexão-ação-reorientação das práticas de cuidado. Ao ampliar a análise para além dos importantes indicadores solicitados pelo Programa Nacional do Controle do Tabagismo, a matriz elaborada dirige-se ao fortalecimento (empowerment) dos envolvidos (profissionais e usuários). Ajuda a estabelecer papéis e responsabilidades na reorientação de aspectos que possam influenciar o desempenho no acesso, acolhida, diagnóstico, tratamento e acompanhamento dos que desejam parar de fumar. / Introduction: Tobacco smoking is a chronic problem and very difficult to face. The improvements in the legislation, the awakening of the society and the smaller social acceptance to tobacco smoking have increased the number of people looking for smoking cessation services. The evaluation of such programs is a complex task, considering the different levels of intervention and the diversity of sceneries and actors involved. The evaluation of smoking cessation programs needs to incorporate participatory tools in order to indicate the program efficiency, and foster transformation actions of the practices. This study sought to configure an evaluation framework capable of contributing to the organization and self-learning of the services addressed to individuals in their attempts to quit smoking by capturing the different contexts present in the intervention sceneries and actors. The research questions were: Which are the indicators that may point out how much a service comes close or is distant from evidence-based practices, guidelines and models of health promotion? Which are the elements that indicate or not the quality of a smoking cessation treatment service? Objective: Developing the indicators framework of a smoking cessation service. For this it was sought to a) identify the experts, users and professionals perceptions about smoking cessation services, b) Characterize the practices and basis for a smoking cessation service c) Build the evaluative logical model of such service c) Formulate the theoretical and practical basis for the construction of an evaluative framework of indicators for a smoking cessation service. Method: Situated in the theoretical model oriented design (theory-driven evaluation) from the perspective of health promotion proposed by Hartz, the methodological trajectory was based on the qualitative and participative approaches as well as in the strategy of the action research. The study setting was the smoking cessation service at a university hospital in São Paulo. The subjects of this study were reference for the NTCP professionals (experts), the professionals who work directly in the service (stakeholders) and service users. The analysis and discussion of the findings were based upon the triangulation of data, correlated with the literature. Results: The outcome of this research was the development of the evaluation framework. It was used the perceptions of experts, and users concerned about the dimensions of structure, process and outcome. The legislation, funding, the extension and coverage, accessibility, facilities, human resources, equipment and supplies were identified for \"structure\". In the dimension \"process\" the categories were: dissemination and uptake, host and active search, the social psychological profile of the users, the network of reference and cross reference, diagnosis, monitoring and educational strategies based on self-care and harm reduction. Within the scope of \"outcomes\" the subjects pointed: the success rate of stop smoking, the regularity of service, treatment adherence, the autonomy, the improvement in quality of life and user satisfaction. Conclusions: We conclude that the evaluative framework constructed has the potential for assessing the service quality and to promote institutional learning and personal / professional development. It contributes to the movement of the reflection-action-reorientation of care practices. By broadening the analysis beyond the important indicators requested by the National Tobacco Control Program, the elaborate framework is targeted to the empowerment of those involved (professionals and patients). It helps to set roles and responsibilities in reorienting the aspects that may influence the access, reception, diagnosis, treatment and monitoring performance of those who want to quit smoking.