INTRODUÇÃO: A exposição contínua desde o nascimento à poluição atmosférica de grandes centros urbanos de origem predominante veicular, contribui para eventos cardiopulmonares em adultos. A inflamação e remodelamento induzidos pelos poluentes podem modular a resposta vascular a mediadores e alterar a sua patência e reatividade contribuindo para eventos isquêmicos. MÉTODOS: Verificar alterações inflamatórias e estruturais nos pulmões e corações de camundongos Swiss machos cronicamente expostos, desde o nascimento até a idade adulta, às câmaras seletivas com filtros (câmara limpa) e sem filtros (câmara poluída) para particulados e gases tóxicos, situadas a 20m de um cruzamento de tráfego intenso da cidade de São Paulo, 24 h/7dias/semana/4 meses. Realizaram-se medidas internas e externas dos poluentes: PM2,5; NO2 e Black Carbon (BC) e análises morfométricas nos pulmões e corações. RESULTADOS: A filtragem da câmara limpa clareou 100% de BC, 52% de PM2,5 e 32% de NO2. Nos pulmões, as alterações predominaram na região peribronquiolar. Os animais submetidos à câmara poluída apresentaram inflamação peribronquiolar caracterizada por aumento do infiltrado perivascular (p=0,022), hiperplasia do epitélio bronquiolar (p=0,037), escore inflamatório total (p=0,015), e diminuição do infiltrado polimorfonuclear na região do septo alveolar distal (p=0.001). A parede dos vasos peribronquiolares não demonstrou alteração da razão lúmen/parede (L/P) entre os grupos (0,094), porém, os animais submetidos à câmara poluída, apresentaram remodelamento estrutural com diminuição de fibras elásticas na adventícia (p= 0,006) e na túnica média (p= 0,008) e das fibras colágenas apenas na adventícia (p= 0,016). No miocárdio, verificamos aumento do número de núcleos por área do VE, sem alteração de peso dos corações entre os grupos (p=0,005). As coronárias dos camundongos expostos à câmara poluída também não demonstraram diferenças na razão L/P, porém a poluição induziu remodelamento através de aumento de fibras colágenas e elásticas na camada adventícia e média dos vasos (p<0.001; p=0,03 respectivamente), mesmo quando categorizados os vasos por seu calibre e por ventrículo separadamente (p<0,001). CONCLUSÃO: A poluição atmosférica da cidade de São Paulo, Brasil, induziu alterações inflamatórias e estruturais nos pulmões e corações dos animais normais expostos desde o nascimento até a idade adulta. A resposta pulmonar caracterizou-se por inflamação e diminuição das fibras da matriz extracelular dos vasos, enquanto as coronárias apresentaram fibrose e elastogênese em toda parede vascular. Esses achados reforçam a hipótese de que a poluição atmosférica de grandes centros urbanos induz alterações silenciosas porém significativas, órgão-específicas, modulando a resposta vascular, podendo contribuir para alteração da patência e reatividade dos vasos e eventos isquêmicos na idade adulta / INTRODUCTION: The continuous exposition since birth to atmospheric pollution of great urban centers originated by vehicles predominantly, contributes to cardiopulmonary events in adults. The remodeling and inflammation induced by airborne pollutants may modulate the vascular response to mediators and alter the vascular patency and reactivity which may contribute to ischemic events. METHODS: To verify the inflammatory and structural alterations of the lungs and heart of Swiss male mice chronically and continuously exposed since birth to adulthood, to selective chambers with (clean) or without (polluted) filter devices for particles and toxic gases, 7days/24h/4 months, located 20m far from a cross-road with heavy traffic in Sao Paulo city downtown. Measurements of PM2,5; NO2 and Black Carbon (BC) inside the chambers and in the external environment and morphometric analyses of the lung and heart were made. RESULTS: Filters cleared 100% of BC, 47% of PM2,5 and 68% of NO2 in the clean chamber. In the lungs, pollutants affected predominantly the peribronchiolar area. Animals submitted to the polluted chamber presented peribronchiolar inflammation characterized by increased perivascular influx (p=0.022), bronchiolar epithelial hyperplasia (p=0.037), total inflammatory scores (p=0.015), and decrement of polymorphonuclear cells infiltration in the distal septa (p=0.001). There was no difference of the lumen/wall ratio (L/W) of peribronchiolar vessels (p=0.094) between groups. However, mice from polluted chamber presented structural remodeling characterized by decrement of elastic fibers in both adventitia (p=0.006) and media layers (p= 0.008) and collagen content in the adventitia (p= 0.016). In the heart, there was an increase of nucleus of myocytes/left ventricle area, but no alteration of the myocardial weight between groups (p=0.005). Although the coronary arterioles from mice exposed to polluted ambient did not show differences of L/W ratio when compared to those from clean ambient, pollutants induced increment of collagen and elastic fibers in the adventitia and media vascular layer (p<0.001; p=0.03 respectively), even when vessels were categorized by caliber and per ventricle chamber separately (p<0.001). CONCLUSION: The continuous exposure to atmospheric pollution of São Paulo city, Brazil, since birth to adulthood, induced inflammatory and structural alterations in the lungs and heart. The lung response was characterized by inflammation and decrement of extracellular matrix fibers while in the heart, there was fibrosis and elastin increment in the coronary arteriolar wall. These results reinforce the hypothesis that urban airborne pollution predominantly generated by traffic, induces silent but significant organ-specific alterations, which may impair vascular patency and reactivity and may contribute to ischemic cardiac events in the adulthood

Este trabalho teve como objetivo analisar as condições meteorológicas favoráveis e desfavoráveis à dispersão de poluentes, com ênfase no ozônio, nas áreas urbanas associadas à Região Metropolitana de São Paulo (RMSP) e a Grande Santiago (GS). Medidas de concentração de estações localizadas em ambas as áreas de estudo foram utilizadas para determinar o comportamento médio, o número de ocorrências de ultrapassagens de padrão de qualidade do ar e o aumento noturno das concentrações de ozônio num período de dez anos. Foi encontrado que o máximo horário acontece próximo das 14 horas (horário local) nas duas regiões, e que existe uma tendência à diminuição no número de ultrapassagens do padrão de qualidade do ar associado a este poluente. Na RMSP é possível observar um máximo secundário durante a madrugada, enquanto que este fenômeno não é claramente observado nos valores médios de concentração na GS. Com dados da Reanálise do NCEP/NCAR foi visto que a ocorrência deste fenômeno está associada a configurações sinóticas específicas na GS, enquanto que na RMSP não existe padrão sinótico específico que diferencie casos com e sem aumento de ozônio noturno. Um novo módulo fotoquímico (NPM), contendo 95 reações foi inserido no modelo BRAMS na tentativa de melhorar o prognóstico das concentrações de poluentes, principalmente em relação ao ozônio. O NPM mostrou melhor desempenho que o módulo fotoquímico original do modelo (SPM; Simple Photochemical Module) para todos os poluentes considerados, salvo o ozônio, para o qual o SPM apresentou melhores índices estatísticos em 5 das 7 estações avaliadas. As características locais associadas à ocorrência simultânea ou não de aumento na concentração de ozônio foram estudadas utilizando o modelo BRAMS com o módulo SPM ativado, sendo verificado que o aumento de ozônio na RMSP está associado, principalmente, ao transporte vertical deste poluente a partir de níveis mais elevados da atmosfera, enquanto que o transporte horizontal é a maior contribuição para o aumento das concentrações de ozônio durante o período noturno na GS. / This work aimed to analyze the favorable and unfavorable meteorological conditions for pollutant dispersion, especially ozone, at the Metropolitan Area of São Paulo (MASP) and the Greater Santiago (GS). Ozone concentration measurements from stations located in both urban areas were used to determinate the mean behavior, the number of standard air quality exceedances and the increase on nocturnal ozone concentration over a 10 years period. It was found that the diurnal maximum occurs around 14 local time in both urban areas, and that there is a diminishment tendency of the total cases of standard air quality exceedances during all period. A secondary maximum of ozone concentration was observed in MASP at night, which was not clearly seen on mean values over GS. By using the NCEP/NCAR Reanalysis data it was seen that the occurrence of this phenomenon is associated to specific synoptic patterns for GS, while there is no specific synoptic pattern for the MASP cases, with or without nocturnal increase in ozone concentrations. A New Photochemical Module (NPM), containing 95 reactions was coupled to BRAMS model in an attempt to improve the prediction of air pollutants, especially ozone. The NPM showed a better performance than the original module, the SPM (Simple Photochemical Module), for all considered pollutants but ozone. For this pollutant, the SPM presents better statistical indexes for 5 of the 7 stations analyzed. The local characteristics related to simultaneous occurrence of nocturnal ozone increase was studied using the SPM-BRAMS model, which showed that the secondary nocturnal maximum of ozone concentrations in MASP are related to vertical transport of this pollutant from higher levels of the atmosphere to the surface, while the horizontal transport is a major contributor to the increase of ozone concentrations in the GS during the night.

Cette étude est consacrée à la modélisation spatio-temporelle de la pollution atmosphérique urbaine en utilisant un ensemble de méthodes statistiques exploitant les mesures de concentrations de polluants (NO2, O3) fournies par un réseau de surveillance de la qualité de l'air (AIRPARIF). Le principal objectif visé est l'amélioration de la cartographie des champs de concentration de polluants (le domaine d'intérêt étant la région d'Île-de-France) en utilisant, d'une part, des méthodes d'interpolation basées sur la structure spatiale ou spatio-temporelle des observations (krigeage spatial ou spatio-temporel), et d'autre part, des algorithmes, prenant en compte les mesures, pour corriger les sorties d'un modèle déterministe (Filtre de Kalman d'Ensemble). Les résultats obtenus montrent que dans le cas du dioxyde d'azote la cartographie basée uniquement sur l'interpolation spatiale (le krigeage) conduit à des résultats satisfaisants, car la répartition spatiale des stations est bonne. En revanche, pour l'ozone, c'est l'assimilation séquentielle de données appliquée au modèle (CHIMERE) qui permet une meilleure reconstitution de la forme et de la position du panache pendant les épisodes de forte pollution analysés. En complément de la cartographie, un autre but de ce travail est d'effectuer localement la prévision des niveaux d'ozone sur un horizon de 24 heures. L'approche choisie est celle mettant en œuvre des méthodes de type réseaux neuronaux. Les résultats obtenus en appliquant deux types d'architectures neuronales indiquent une précision correcte surtout pour les 8 premières heures de l'horizon de prédiction / This study is devoted to the spatio-temporal modelling of air pollution at a regional scale using a set of statistical methods in order to treat the measurements of pollutant concentrations (NO2, O3) provided by an air quality monitoring network (AIRPARIF). The main objective is the improvement of the pollutant _elds mapping using either interpolation methods based on the spatial or spatio-temporal structure of the data (spatial or spatiotemporal kriging) or some algorithms taking into account the observations, in order to correct the concentrations simulated by a deterministic model (Ensemble Kalman Filter). The results show that nitrogen dioxide mapping based only on spatial interpolation (kriging) gives the best results, while the spatial repartition of the monitoring sites is good. For the ozone mapping it is the sequential data assimilation that leads us to a better reconstruction of the plume's form and position for the analyzed cases. Complementary to the pollutant mapping, another objective was to perform a local prediction of ozone concentrations on a 24-hour horizon; this task was performed using Artificial Neural Networks. The performance indices obtained using two types of neural architectures indicate a fair accuracy especially for the first 8 hours of prediction horizon

L’aérosol organique secondaire (AOS), fraction majoritaire de l’aérosol submicronique, joue un rôle important sur la santé, l’environnement et le climat. L’évaluation de son impact constitue un véritable enjeu pour la communauté scientifique. Toutefois, nos connaissances actuelles sur les processus de formation d’AOS et sa composition chimique sont encore très lacunaires, et en l’occurrence, limitent le développement des modèles atmosphériques permettant de quantifier les impacts des AOS sur la qualité de l’air et le système climatique. Ainsi, l’objectif de ce travail est de produire un ensemble de données expérimentales fournissant des points de contrainte afin d’évaluer et d’améliorer les modèles. Pour ce faire, la formation d’AOS a été étudiée à partir de la photooxydation d’un précurseur modèle, le n-dodécane, dans la chambre de simulation atmosphérique CESAM. La composition chimique a été élucidée par des techniques spectrométriques et chromatographiques permettant d’identifier les différentes espèces constituant la phase gazeuse et particulaire. En particulier, de nouveaux mécanismes en phase condensée ont été proposés afin d’expliquer la formation des acides carboxyliques et des lactones, identifiés pour la première fois dans l’AOS d’un alcane. Ces derniers pourront être implémentés dans les modèles. Une grande diversité de conditions environnementales, telles que la température, l’humidité relative et la présence/absence de particules préexistantes, a été prise en compte dans ces travaux. Notamment, l’étude de l’influence de la température a mis en évidence une faible sensibilité de ce paramètre sur les rendements de production d’AOS. Tandis que l’étude sur l’effet de l’humidité relative, elle, a montré que l’ajout d’eau dans le système réactionnel au-delà de 5% abaisse les rendements d’AOS de près d’un facteur 2 en comparaison à des conditions sèches. Ainsi, la formation potentielle d’AOS sous ces différentes conditions a permis d’aboutir à des paramétrisations directement utilisables par les modélisateurs. Une caractérisation des effets de paroi dans CESAM, i.e. les pertes en phase gazeuse et particulaire, a également été menée / Secondary Organic Aerosol (SOA), the major fraction of the submicron aerosol, plays a key role on health, environment and climate. The evaluation of its impacts is a real challenge for the scientific community. Our current knowledge of SOA formation processes and chemical composition is still very deficient and limit the development of atmospheric models to quantify the impacts of SOA on air quality and climate system. Therefore, the aim of this work is to produce a set of experimental data to use to constrain and improve the models. To do that, the SOA formation has been studied from the photooxidation of a model precursor, n-dodecane, in the CESAM environmental chamber. The chemical composition has been investigated by spectrometric and chromatographic techniques which allowed us to identify the reaction products constituting the gaseous and particulate phases. In particular, new condensed phase mechanisms have been proposed to explain the formation of carboxylic acids and lactones, identified for the first time. These could be implemented in the models. A wide variety of environmental conditions, such as temperature, relative humidity and the presence/absence of preexisting particles, have been taken into account in this work. The study of the temperature influence has shown a low sensitivity of this parameter on the SOA production. While the study relative humidity effect has shown that adding water to the reaction system beyond 5% lowers SOA yields by almost a factor of 2 in comparison to dry conditions. The SOA formation potential, under these conditions, has been evaluated, and resulted in parameterizations which could be useful for modelers. Furthermore, a characterization of the wall effects in CESAM, i.e. gas and particulate phase wall losses, has been carried out

La pollution atmosphérique particulaire constitue l'un des facteurs de risques impliqués dans l'incidence élevée de pathologies respiratoires et cardio-vasculaires. Afin d'intégrer les variations liées aux sources d'émission et aux saisons, des aérosols atmosphériques particulaires (PM₂.₅) ont été prélevés à Dunkerque sous influence urbaine (U) et/ou industrielle (I) et à Rubrouck sous influence rurale (R), au printemps-été 2008 (1) et à l'automne 2009 (2). La caractérisation physico-chimique des six échantillons particulaires a montré une granulométrie fine (79 à 98 % < PM₂.₅) et des aires spécifiques de 3 à 6 m²/g. Leurs concentrations en espèces ioniques différaient, comme celles en éléments métalliques majoritaires (Fe > Al > Mn > Zn > Cu > Ti ; I > U > R). Des différences ont également été observées quant à leurs concentrations en éléments organiques (HAP : I2 > U2 > I1 > U1 > R2 > R1 ; PCDD/F et PCB : I2 > I1 > U2 > U1 > R1 > R2) ; eu égard des influences considérées (PMindustriel > PMurbain > PMrural), et des saisons de prélèvements. Après évaluation de la cytotoxicité globale in vitro des échantillons particulaires, dans les cellules épithéliales bronchiques humaines (BEAS-2B), nous avons montré la capacité des composés organiques absorbés à la surface de ces particules à induire l'expression génique des enzymes de métabolisation (CYP 1A1 et 1B1, et à moindre mesure NQO1). De plus, la production excessive des ERO intracellulaires dans les cellules BEAS-2B exposées aux six PM₂.₅ a induit des dommages oxydatives (production de MDA, formation de 8-OHdG et/ou altération du statut de glutathion). Un développement d'une réponse inflammatoire excessive a aussi été observé par l'expression et/ou la sécrétion significative des cytokines (notamment IL-6 et IL-8). Ces réponses ont été observées d'une manière dose et/ou temps dépendante. En revanche, nous n'avons pu observer de mutations géniques au niveau des acteurs principaux de la voie EGFR/KRAS/BRAF. / Particulate air pollution constitutes one of the major risk factors implicated in the high incidence of respiratory and cardio-vascular pathologies. In order to integrate the variation linked to emission sources and seasons, atmospheric particulate matter (PM₂.₅) were collected at Dunkerque under urban (u) and/or industrial influence (I) and at Rubrouck (R) under rural influence, in spring-summer 2008 and autumn-winter 2009. The physico-chemical characterization of the six particulate samples has shown a fine granulometry (79 to 98 % < PM₂.₅) and a specific surface of 3 to 6 m²/g. Their concentrations in ionic species as well as in major metallic elements were different (Fe > Al > Mn > Zn > Cu > Ti ; I > U > R). Differences were also been observed in their organic element constitution (PAH : I2 > U2 > I1 > U1 > R2 > R1 ; PCDD/F and PCB : I2 > I1 > U2 > U1 > R1 > R2) with respect to considered influences (PMindustriel > PMurban > PMrural) and sampling seasons. After in vitro evaluation of particulate samples global cytotoxicity in human bronchial epithelial cells (BEAS-2B), we had shown the capacity of the organic components absorbed to the surface of these particles to induce gene expression of xenobiotic-metabolizing enzymes (CYP 1A1 and 1B1, and to a lesser extent, NQO1). Moreover, excessive intracellular production of reactive oxygen species within BEAS-2B cells exposed to the six PM₂.₅ samples induced oxidative damage (MDA production, 8-OHdG formation and/or glutathione status alteration). There was also a development of an excessive inflammatory response based on statistically significant increases in gene expression and/or protein secretion of cytokines (notably IL-6 and IL-8). These obtained responses were dose and/or time dependant. However, we couldn't observe mutations in the principal acting genes in the pathway EGFR/KRAS/BRAF.

La pollution de l'environnement, et particulièrement la pollution atmosphérique et son possible impact sur la santé humaine, suscite un intérêt grandissant dans les pays en voie de développement. Ce travail de thèse s'inscrit dans cette thématique et constitue une étude pionnière en Afrique, et au Bénin plus particulièrement. Nos résultats ont montré que l'essence utilisée à Cotonou était de piètre qualité, caractérisée par l'absence d'additifs et par une forte concentration en benzène, et pouvait être à l'origine de la dégradation de la qualité de l'air de la ville. De même, l'analyse d'échantillons de particules (PM₂․₅ et PM>₂․₅) prélevés dans le quartier de St Michel à Cotonou, a mis en exergue un taux anormalement élevé de particules en suspension dans l'air. La caractérisation physicochimique de ces particules a montré la présence d'un cocktail de composés chimiques (ions, métaux, COVs, paraffines, HAPs, etc.), en proportion plus élevées dans les particules fines PM₂․₅. L'appareil respiratoire constituant la principale voie d'exposition de l'Homme à ces particules atmosphériques, leur potentiel toxique a été évalué au travers d'une étude in vitro menée sur des cellules épithéliales bronchiques humaines (BEAS-2B). Il a été ainsi démontré les propriétés cytotoxiques des deux échantillons de particules ainsi que leur capacité à induire l'expression génique des enzymes de métabolisation des composés organiques et à générer un stress oxydatif. Le déclenchement du processus inflammatoire via l'induction de l'expression génique et la sécrétion protéique de cytokines et l'apparition de modifications dans la voie de l'acide arachidonique (leucotriènes, prostaglandine, thromboxane) ont été notés. Enfin l'approche comparative des PM₂․₅ prélevées au niveau de trois villes d'Afrique de l'Ouest a permis de mettre en évidence des caractéristiques proches au Bénin, en Côte d'Ivoire et au Sénégal et la contribution des émissions du trafic routier dans la pollution de l'air. / Air pollution and its adverse health effects have shown a growing interest in developing countries. This study deals with this subject and is one of the first conducted in African countries, particularly in Benin. Our results showed that the quality of gasoline used in cotonou was poor, characterized by the absence of additive and a high concentration of benzene. Thus, it could be responsible for the degradation of the city air quality. Therefore, particulate matter samples (PM₂․₅ and PM>₂․₅) were collected in St Michel neighborhood at Cotonou and results showed very high levels of particles in the ambient air. Physicochemical characterization of these particles revealed a presence of various chemicals compounds (ions, metals, VOCs, paraffins, PAHs, ect.) in higher proportion in PM₂․₅ than PM>₂․₅. The respiratory system, the main way of exposure to these airborne particles, was investigated through an in vitro study assessing the toxic potential of PM on human bronchial epithelial cells (BEAS-2B). It has been demonstrated that the two types of particules have cytotoxic properties and ability to induce gene expression of organic compounds metabolizing enzymes and to generate oxidative stress. These particles have triggered the inflammatory process through the induction of gene expression and protein secretion of cytokines, and changes in the arachidonic acid pathway (leukotrienes, prostaglandin, and thromboxane). Finally, comparative approach for PM₂․₅ sampled in three West African cities highlighted the closeness of particles characteristics in Benin, Côte d'Ivoire and Senegal, and a significant contribution of road traffic emissions in the air pollution.

La pollution atmosphérique et les évènements météorologiques sont reconnus pour avoir des graves conséquences sur la santé telles que la mortalité cardiovasculaire et respiratoire, et par conséquent représentent un enjeu majeur de santé publique. Des travaux plus récents ont suggéré un effet des expositions à ces facteurs environnementaux durant la période intra-utérine. La vie fœtale est déterminante pour le bon développement de l’enfant. L’exposition maternelle aux facteurs environnementaux pendant la grossesse pourrait avoir des conséquences sur les issues de grossesse et la santé à court ou long terme. Par ailleurs, les mécanismes biologiques qui pourraient expliquer l’effet des expositions environnementales sur les issues de grossesse indésirables sont à l’heure actuelle très peu connus. Les objectifs de la thèse étaient : 1) d’étudier les associations entre d’une part la température et l’humidité relative pendant la grossesse et d’autre part le poids de naissance, la durée de gestation et la prématurité ; 2) d’étudier les associations entre l’exposition maternelle aux polluant de l’air et aux évènements météorologiques pendant la grossesse et la méthylation de l’ADN placentaire en utilisant A) une approche agnostique et B) une approche avec a priori basée sur l’intégration de connaissances biologiques. Le premier objectif s’est appuyé les données issues de deux cohortes mère-enfant, EDEN (avec un recrutement à Poitiers et Nancy en 2003-2006) et PELAGIE (Bretagne, 2002-2006) soit au total 5185 couples mère-enfant ; le deuxième objectif s’est appuyé sur un échantillon de 668 femmes de la cohorte EDEN chez qui le placenta a été prélevé et le niveau de méthylation de son ADN caractérisé. Les données quotidiennes de température et d’humidité ont été obtenues de Météo-France et l’exposition à la pollution atmosphérique a été estimée par un modèle de dispersion atmosphérique. Différentes fenêtres d’exposition au cours de la grossesse ont été considérées. Des échantillons de placenta centraux ont été collectés à l’accouchement et la méthylation de l’ADN a été analysée en utilisant la puce Illumina 450K. Pour répondre au premier objectif, des modèles de régression linéaire et des modèles de Cox ont été réalisés. Pour répondre au second objectif, des modèles de régression linéaire robuste, notamment à l’échelle du génome entier, ont été réalisés en appliquant des méthodes de correction de tests multiples telles que Bonferroni et Benjamini-Hochberg. Nos résultats suggèrent un effet délétère de la température et l’humidité sur le poids de naissance et ne mettent pas en évidence d’association entre pollution atmosphérique et issues de grossesse. L’exposition aux polluants atmosphériques (NO2 et PM10) pendant la grossesse était associée à une diminution de la méthylation de l’ADN placentaire pour les gènes ADORA2B et ADARB2 ; le premier gène étant connu pour être potentiellement impliqué dans la pré-éclampsie et l’hypoxie de la femme enceinte et le deuxième étant potentiellement impliqué dans les troubles métaboliques chez l'adulte tels que la circonférence abdominale et l'IMC. Les résultats des approches agnostique et avec a priori étaient cohérents pour le gène ADORA2B. Nous n’avons pas identifié d’association entre les conditions météorologiques et la méthylation de l’ADN placentaire. A notre connaissance, nous sommes les premiers à avoir étudié l’association entre la méthylation de l’ADN dans le tissu placentaire et l’exposition prénatale aux polluants de l’air et aux conditions météorologiques en utilisant des données de l’épigénome entier. Ce travail de thèse ouvre de nouvelles voies possibles concernant les mécanismes d’actions des polluants environnementaux et fournit des pistes quant aux effets à long terme possibles de ces expositions. / Nowadays, air pollution and weather conditions represent a major public health issue. It is recognized that they may have serious consequences for health especially in the most sensitive populations such as pregnant women. More recent studies have suggested an effect of exposure to these environmental factors during the fetal period. Fetal life is a critical period for the healthy development of the child. Maternal exposure to environmental exposures during pregnancy could have serious consequences on pregnancy outcomes and short- and long- term health. Furthermore, the biological mechanisms that could explain the effect of environmental exposures on adverse pregnancy outcomes are largely unknown up to now. The objectives of the thesis were: 1) to study the association between maternal exposure to temperature and relative humidity during pregnancy and birth weight, gestational duration and preterm birth; 2) to study the association between maternal exposure to air pollutants and meteorological conditions during pregnancy and placental DNA methylation using A) an agnostic approach and B) a priori approach based on integration of biological knowledge. The first part of this work relied on data from two mother-child cohorts EDEN (Poitiers and Nancy, 2003-2006) and PELAGIE (Britain, 2002-2006) corresponding to 5185 mother-infant pairs analyzed; and the second part relied on a sample of the EDEN cohort for which methylation data were available (n = 668). Daily data of temperature and humidity were obtained from Météo-France and pollution data were obtained using a dispersion model. Their exposure was averaged over different periods during pregnancy. Central placenta samples were collected at delivery and DNA methylation was analyzed using Illumina 450K chip. For the first objective, linear regression models and Cox models were used. For the second objective, robust linear regression models, especially across the genome-wide, were used and correction methods for multiple testing such as Bonferroni and Benjamini-Hochberg were applied. Our results suggest a deleterious effect of temperature and relative humidity on birth weight and did not show an association between air pollution and pregnancy outcomes. Exposure to air pollutants (NO2 and PM10) during pregnancy was associated with a decrease in placental DNA methylation for ADORA2B and ADARB2 genes; the first gene is known to be potentially involved in preeclampsia and hypoxia of the pregnant woman and the second being potentially involved in metabolic disorders in adults such as abdominal circumference and BMI. The results of agnostic and a priori approaches were consistent for ADORA2B gene. We did not found association between weather conditions and placental DNA methylation. To our knowledge, we are the first to study the association between DNA methylation in the placental tissue and prenatal exposure to air pollutants and weather conditions using data from the entire epigenome. This work opens up new possible pathways regarding mechanisms of action of environmental pollutants and provides pointers as to the possible long-term effects of these exposures.

[pt] Este trabalho tem como finalidade determinar a concentração em massa, caracterizar quimicamente as espécies presentes e identificar as possíveis fontes das amostras de material particulado (MP10 e MP2,5) coletados em locais com (Gericinó, Lagoa e Copacabana) e sem (Botafogo) a influência dos Jogos Olímpicos, no Rio de Janeiro. As amostras de MP foram disponibilizadas pelo Instituto Estadual do Ambiente (INEA) referente ao ano de 2016, sendo os meses de julho a setembro considerados como a temporada Olímpica. A caracterização química das amostras foi realizada por ICP-MS e Cromatografia de Íons (CI). Durante a temporada Olímpica, em 2016, foram reduzidos cerca de 26 porcento de MP10, quando comparados aos anos anteriores na mesma época do ano, por outro lado, o MP2,5 não foi reduzido. De todos os íons solúveis em água analisados, as maiores concentrações foram obtidas para o NO3-, SO4 2- e Na positivo nas duas frações de MP. As altas concentrações dos íons NO3 - e SO4 2- sugerem a presença de fontes antropogênicas. A partir do cálculo de nss (non-sea salt) foi possível observar que os íons Ca2 positivo, K positivo e SO4 2- tiveram uma contribuição marinha baixa. Os metais Fe, Cu e Ti foram os majoritários em todas as amostras nas duas frações de MP, enquanto que elementos como Mn, Pb, V e Ni foram detectados como minoritários. Correlações acima de 0,90 foram observadas entre Ti-Mn e Ti-Fe, sugerindo emissões de ressuspensão do solo e fortes correlações entre V-Ni e VPb mostram a influencia veicular como principal fonte. Finalmente, foi possível observar que houve uma influência dos Jogos Olímpicos na concentração em massa e de algumas espécies no MP2,5, enquanto que no MP10 não foi observada qualquer correlação. / [en] The main aim of this work was to determine the mass concentration, chemically characterize the species present and identify the possible sources of samples of particulate matter (PM10 e PM2.5) collected at sites with (Gericinó, Lagoa e Copacabana) and without (Botafogo) the influence of the Olympic Games in Rio de Janeiro. The PM samples were obtained from the Instituto Estadual do Ambiente (INEA) relative to the year 2016. The Olympic seasons considered were July to September of 2016. The chemical characterization of the samples was performed by ICP-MS and ion chromatography (IC). PM10 during the Olympic period were reduced 26 percent, when compared to previous years at the same time of the year. On the other hand, PM2.5 was not reduced during the Olympic period. Of all the water-soluble ions analyzed, the highest concentrations were obtained for NO3-, SO42- and Na plus in both fractions of PM. High concentrations of NO3 - and SO4 2- suggest the presence of anthropogenic sources. From calculation of non-sea salt was possible to observe that Ca2 plus, K plus and SO4 2- had a low marine contribution. Fe, Cu and Ti were the majority metals of all samples in both fractions of PM, while Mn, Pb, V and Ni were detected as minorities. Correlations above 0.90 are observed between Ti-Mn and Ti-Fe, suggested soil resuspension emissions. Strong correlations coefficients between V-Ni and V-Pb show the vehicular influence as the main source. Finally, it was possible to observe an influence of the Olympic Games in mass concentration and some species in PM2.5, while in PM10 no correlation was observed.

Today, outdoor air quality occupies an important place into civic dialogue because of the many impacts of atmospheric pollution on health. Different legislations and strategies have thus been implemented across the world to improve outdoor air quality. Analysing and comparing the different strategies can help adopting the best practices in favour of air quality. In France, in particular, the national air quality policy is reflected at a regional scale through legislative documents called Atmosphere Protection Plans (PPAs). The analysis of such a document thus represents a powerful way to assess a regional air quality policy. Here, Normandie’s PPA has been analysed through a literature review, working meetings as well as qualitative interviews. The study highlighted that Normandie’s air quality policy had to answer a complex legislative ecosystem of international, national and local documents. The analysis also underlined that the questions of the perimeter of action of the policy and the targeted pollutants were as central as the measures implemented to improve air quality. The working meetings and the qualitative interviews led to consensus that Normandie’s air quality policy should target 3 atmospheric pollutants: nitrogen dioxide, particulate matter 10 and particulate matter 2.5. If road traffic has been identified as the major emitting source of the first, particulate matter emitting sources were pointed as varied and multi-sectoral. Finally, some measures of Normandie’s air quality policy appeared to be particularly efficient and advanced, such as agricultural measures. Yet, many difficulties were encountered when implementing several measures of the policy. The main difficulties were the lack of financial resources, the lack of project leader and the lack of technical expertise. More than a basic analysis of an air quality public policy, these results can also be perceived as a sharing of experience on how a region addresses air quality issues. Because a work of collection of best practices and best strategies to improve air quality is more than ever needed, further research can build on this study to elaborate a relevant air quality policy. / Luftkvaliteten visar den antropogena nedbrytningen av det naturliga tillståndet för luft. Detta ämne har spelat en allt viktigare roll i den offentliga debatten under de senaste decennierna, på grund av de olika effekterna som luftföroreningar har på hälsan. I denna masteruppsats har Normandies politik för luftkvalitet analyserats. I Frankrike regleras nationell luftkvalitetspolitik i regional skala genom lagstiftningsdokument som kallas Atmosphere Protection Plan (PPA). Analysen av detta dokument gör det möjligt att bedöma den regionala luftkvalitetspolitiken. Således har hela studien baserats på analysen av Normandies PPA.  Här har Normandies PPA analyserats genom litteraturöversikt, arbetsmöten och kvalitativa intervjuer. Först och främst belyste litteraturöversikten att Normandies PPA måste ta hänsyn till ett komplext lagstiftningsekosystem, allt från internationell till lokal skala. I synnerhet är Normandies PPA-huvudmål att uppnå de tröskelvärden som definieras av de europeiska direktiven.  I ett andra steg tillät en granskning av PPA från sex franska regioner att jämföra Normandies luftkvalitetspolitik med andra regioners politik. Under denna fas har såväl strukturer dokumenterats som de presenterade åtgärderna utvärderats med avseende på strukturerna och åtgärderna för de andra PPA. I synnerhet har återkommande kategorier och underavsnitt identifierats i de sex PPA. Dessutom tycktes motiveringen av applikationomkrets vara central, liksom de riktade atmosfäriska föroreningarna. På samma sätt tillät jämförelsen av åtgärderna för de sex PPA att identifiera de relevanta och banbrytande åtgärderna i Normandies PPA, som tillhör hamnsektorn och de sektorsövergripande åtgärderna. Omvänt verkade åtgärderna av Normandies PPA vara otillfredsställande inom industri- och transportsektorn.  En mer fördjupad analys genomfördes genom arbetsmöten och kvalitativa intervjuer. Flera frågor har bedömts, till exempel applikationomkrets och PPAs struktur. I synnerhet har man dragit slutsatsen att minskningen av applikationomkretsen som Normandie avsåg var relevant och förhindrade PPAs komplikationer. Dessutom påpekade deltagarna att om Normandies PPA-struktur var ganska tydlig, saknades fortfarande viktiga underavsnitt i Normandies PPA och de bör läggas till.  Arbetsmötena liksom de kvalitativa intervjuerna gjorde det också möjligt att ta upp frågan om de riktade föroreningarna och deras källor. Alla deltagare och intervjuade gick med på att rikta in NO2, PM10 och PM2.5 i Normandies PPA. Integrationen av SO2 och O3 har dock diskuterats mer, den första har endast släppts ut i skadlig mängd under industriella olyckor, och den andra var för svår att hantera eftersom den är en sekundär förorening. När det gäller utsläppskällorna visade studien att en hög atmosfärisk koncentration av NO2 främst berodde på vägtrafik. Utsläppskällorna PM10 och PM2.5 identifierades som mer varierade och flersektoriella.  Slutligen tillät de kvalitativa intervjuerna att avgöra vilka åtgärder av Normandies PPA som har slutförts eller inte, och att identifiera varför. Åtgärder inom jordbrukssektorn nämndes som de mest avancerade åtgärderna i Normandies PPA. Omvänt har två åtgärder övergivits helt, en inom hamnsektorn, den andra inom transportsektorn. Några skäl som förklarade varför alla åtgärder inte har genomförts var bristen på ekonomiska resurser, bristen på projektledare och bristen på teknisk expertis. Mer allmänt verkar det vara avgörande att involvera de olika intressenterna från varje utsläppssektor och sätta dem runt ett bord för att skapa effektiva åtgärder till förmån för luftkvaliteten.

As ações decorrentes das atividades econômicas e industriais têm provocado alterações na biosfera, resultando na quase duplicação da concentração de Gases de Efeito Estufa (GEE) na atmosfera durante o período de 1750 a 1998. A alteração da concentração dos GEE poderá desencadear um aumento da temperatura média no planeta entre 1,4 e 5,8°C nos próximos cem anos (IPCC, 2001a). Para tratar do problema do efeito estufa e suas possíveis conseqüências sobre a humanidade foi estabelecida em 1992, durante a Rio 92, a Convenção Quadro das Nações Unidas sobre Mudanças Climáticas. A Conferência das Partes realizada em Quioto em 1997 destaca-se como uma das mais importantes, uma vez que durante sua realização foi estabelecido um acordo onde se encontram definidas metas de redução da emissão de GEE para os países do ANEXO B (países do ANEXO I com compromissos de redução das emissões de GEE), além de critérios e diretrizes para a utilização dos mecanismos de mercado. Este acordo ficou conhecido como Protocolo de Quioto e estabelece que os países industrializados devem reduzir suas emissões em 5,2% abaixo dos níveis observados em 1990 entre 2008-2012 (primeiro período de compromisso). O Protocolo criou o Mecanismo de Desenvolvimento Limpo (MDL). A idéia do MDL consiste em que cada tonelada de CO2 deixada de ser emitida, ou retirada da atmosfera por um país em desenvolvimento, poderá ser negociada no mercado mundial através de Certificados de Emissões Reduzidas (CER). Esta tese teve como objetivo geral caracterizar o "mercado de carbono", em especial a participação do Brasil através do MDL. Para tanto foi feita uma análise de como este mercado está sendo formado e como deverá ser sua evolução até a possível formação de mercados futuros. Os objetivos específicos foram: 1) Determinar o tamanho do mercado global e a participação do Brasil (através do MDL) em diversos cenários; e, 2) Analisar se os CER gerados em projetos de MDL, em especial por projetos de seqüestro de carbono, poderiam se tornar uma "commodity ambiental" ou não. Ficou claro que o mercado de carbono já é uma realidade, porém encontra-se em um estágio inicial de sua formação. Para estimar o tamanho do mercado utilizou-se o Modelo CERT (Carbon Emission Reduction Trade). Nos cenários de referência do Modelo a maior participação brasileira no mercado de CER foi de apenas 3,4% (Cenário 7), através da venda de 14,4 milhões de toneladas de carbono, gerando um receita de US$ 237 milhões ao custo de US$ 106,3 milhões. O lucro de todos os projetos de MDL no Brasil foi de US$ 130,7 milhões. Nos cenários alternativos a maior participação foi de 17,8% (Cenário Alternativo 7), através da venda de 32,1 milhões de toneladas de carbono, gerando um receita de US$ 525,6 milhões ao custo de US$ 198 milhões. O lucro de todos os projetos de MDL no Brasil neste caso foi de US$ 327,6 milhões. / The economic and industrial anthropogenic activities are increasing the Green House Gas (GHG) atmospheric concentration. These gases can increase the atmosphere temperature in 1.4 to 5.8°C in the next hundred years (IPCC, 2001a). To solve this problem was created in 1992 the United Nations Framework Convention on Climate Change. The Conference of the Parties held at Kyoto in 1997 was one of the most important, since it created an international agreement about the GHG emission reductions to the ANNEX B countries. This agreement is called the Kyoto Protocol and it determine that the industrialized countries should decrease the GHG emissions in 5,2% below the 1990 levels between 2008-2012 (first period commitment). The Protocol also created the Clean Development Mechanism (CDM). The idea of the CDM is that each tone of CO2 that is reduced or sequestered from the atmosphere by a developing country can be negotiated through Certified Emission Reduction (CER).This thesis had the main objective of understand the "carbon market", in special the Brazilian participation through the CDM. The specific objectives was: 1) Determine the size of the global market and the Brazilian participation (through the CDM) in different scenarios; and, 2) To analyze if the CER created by forest projects can be a environmental commodity. It was clear that the carbon market exists but is in an initial phase. To estimate the size of the market the CERT (Carbon Emission Reduction Trade) Model was used. In the reference scenarios the best Brazilian participation, through the CER, was only 3.4% (Scenario 7), selling 14.4 millions tons of carbon, with a revenue of US$ 237 millions and costs of US$ 106.3 millions. The profits of all CDM projects in Brazil was US$ 130,7 millions. In the alternative scenarios the best Brazilian participation was 17.8% (Alternative Scenario 7), selling 32.1 millions tons of carbon, with a revenue of US$ 525.6 millions and costs of US$ 198 millions. In this case the profits of all CDM projects in Brazil was US$ 327.6 millions.