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Particulate air pollution is known to exacerbate respiratory diseases, such as asthma and chronic obstructive pulmonary disease, in humans. It has been proposed that transition meta ls from inhaled particles may play a role in this exacerbation by generating radical species leading to damage in the lungs. The aim of this research was to determine the role that iron from particulate air pollution played in the generation of reactive oxygen species and subsequently the induction of inflammatory mediators in cells in culture. The production of reactive oxygen species by particulate air pollution was found to be dependent on the mobilization of iron from the particles by chelators, such as the physiologically relevant citrate. The amount of iron mobilized from the combustion particulate, coal fly ash, was dependent on the type of coal used to generate the fly ash and was greatest in the smallest size fraction collected for three different coal types. In addition, the amount of iron mobilized from coal fly ash by citrate correlated closely with the amount mobilized in human lung epithelial (A549) cells, as indicated by induction of the iron storage protein, ferritin. The amount of the proinflammatory cytokine, interleukin-8, secreted in response to coal fly ash treatment varied with the amount of iron mobilized intracellularly from the particles, with the greatest response to the smaller size fractions which released the largest amounts of iron. There was a direct relationship, above a threshold level of bioavailable iron, between the level of interleukin-8 and bioavailable iron in cells treated with coal fly ash. Tetramethyl thiourea and dimethyl sulfoxide prevented the increased production of interleukin-8 by human lung epithelial cells treated with coal fly ash, suggesting the role of a radical species in the induction of this inflammatory mediator. The mobilization of iron from coal fly ash by citrate or in human lung epihelial cells, as well as the induction of interleukin-8, did not correlate with the total amount of iron in the particles. Instead, preliminary results suggest that these measured values vary directly with the amount of iron contained in the aluminosilicate fraction of the fly ash.

No presente trabalho, é avaliada a qualidade do ar interno com ênfase na concentração de aerodispersóides presentes em edifícios comerciais e residenciais com sistema de ventilação natural ou condicionamento de ar. De fato, algumas doenças de origem ocupacional são causadas pela inalação de aerodispersóides nocivos à saúde. O método utilizado para avaliar a qualidade do ar interno nos edifícios comerciais e residenciais consistiu primeiramente em caracterizar os medidores de aerodispersóides e em seguida passou-se para a análise das concentrações e das características ambientais. A pesquisa mediu a concentração de aerodispersóides em edifícios com sistemas de ventilação diferentes (1a fase), e identificou as principais fontes de emissão de aerodispersóides em um apartamento residencial (2a fase). Observou-se que as concentrações obtidas na pesquisa estão acima dos valores recomendados na RE n° 9 (ANVISA, 2003) e por Morawska et al. (1999) que atribuem valores de 80 µg/m³ e 7.400 part./cm³, para concentrações médias em massa e em número, respectivamente. Com base nas observações acima, chegou à conclusão que as concentrações médias em massa e em número de aerodispersóides, durante as atividades domésticas (cozimento, reforma, limpeza, entre outras), foram várias vezes maiores do que as concentrações obtidas em ambientes com atividades profissionais ou com menor ocupação durante o dia. / This paper is the result of quality evaluation of indoor air quality with emphasis on the concentration of aerodispersoid in commercial and residential buildings with natural ventilation or air conditioning systems. In fact, some of the occupational diseases are caused by the inhalation of aerodispersoids hazardous to health. The method applied to evaluate the indoor air quality in commercial and residential buildings consisted firstly of characterizing the aerodispersoid measuring devices and subsequently analyzing the concentration levels and environmental characteristics. This research measured the concentration of aerodispersoids in buildings equipped with a variety of ventilation systems (phase1) and next it identified the main emission sources in a residential apartment (phase 2). It was observed that the concentration levels measured were above the specifications recommended by RE n° 9 (ANVISA, 2003) and by Morawska et al. (1999) which attribute values of 80 µg/m³ and 7.400 part./cm³, for average concentration in mass and number respectively. Based on the above information it was concluded that the average concentration levels of aerodispersoids in mass and number in home related activities (cooking, restoration, cleaning, etc) were many times higher than the concentration levels found in business environments or in environments with less occupation during the day.

No presente trabalho, é avaliada a qualidade do ar interno com ênfase na concentração de aerodispersóides presentes em edifícios comerciais e residenciais com sistema de ventilação natural ou condicionamento de ar. De fato, algumas doenças de origem ocupacional são causadas pela inalação de aerodispersóides nocivos à saúde. O método utilizado para avaliar a qualidade do ar interno nos edifícios comerciais e residenciais consistiu primeiramente em caracterizar os medidores de aerodispersóides e em seguida passou-se para a análise das concentrações e das características ambientais. A pesquisa mediu a concentração de aerodispersóides em edifícios com sistemas de ventilação diferentes (1a fase), e identificou as principais fontes de emissão de aerodispersóides em um apartamento residencial (2a fase). Observou-se que as concentrações obtidas na pesquisa estão acima dos valores recomendados na RE n° 9 (ANVISA, 2003) e por Morawska et al. (1999) que atribuem valores de 80 µg/m³ e 7.400 part./cm³, para concentrações médias em massa e em número, respectivamente. Com base nas observações acima, chegou à conclusão que as concentrações médias em massa e em número de aerodispersóides, durante as atividades domésticas (cozimento, reforma, limpeza, entre outras), foram várias vezes maiores do que as concentrações obtidas em ambientes com atividades profissionais ou com menor ocupação durante o dia. / This paper is the result of quality evaluation of indoor air quality with emphasis on the concentration of aerodispersoid in commercial and residential buildings with natural ventilation or air conditioning systems. In fact, some of the occupational diseases are caused by the inhalation of aerodispersoids hazardous to health. The method applied to evaluate the indoor air quality in commercial and residential buildings consisted firstly of characterizing the aerodispersoid measuring devices and subsequently analyzing the concentration levels and environmental characteristics. This research measured the concentration of aerodispersoids in buildings equipped with a variety of ventilation systems (phase1) and next it identified the main emission sources in a residential apartment (phase 2). It was observed that the concentration levels measured were above the specifications recommended by RE n° 9 (ANVISA, 2003) and by Morawska et al. (1999) which attribute values of 80 µg/m³ and 7.400 part./cm³, for average concentration in mass and number respectively. Based on the above information it was concluded that the average concentration levels of aerodispersoids in mass and number in home related activities (cooking, restoration, cleaning, etc) were many times higher than the concentration levels found in business environments or in environments with less occupation during the day.

Les particules fines atmosphériques (PF) sont capables de pénétrer dans les poumons où certains composés transportés peuvent interagir avec les cellules pulmonaires et atteindre la circulation sanguine. L'exposition aux PF affecte particulièrement les populations sensibles telles que les personnes agées. Cette thèse s'inscrit dans une démarche d'identification des effets des PF sur les lymphocytes T humains (LT) tout en visant à déterminer des biomarqueurs liés à l'exposition et à évaluer la variation de la réponse cellulaire en fonction de l'âge. Des LT ont été isolés de prélèvements sanguins de 91 volontaires appartenant à trois classes d'age (20-30, 45-55, 70-85 ans) puis exposés ex vivo pendant 72h à 45 µg/µl de PF collectées à Dunkerque. Les étapes d'isolement, purification et activation des LT ont d'abord été optimisées. Suite à la caractérisation de la population échantillonnée, une population d'étude homogène a été sélectionnée ( 10 sujets / classe d'âge). Nous avons mis en évidence une induction génique d'enzymes impliquées dans l'activation métabolique des HAP identifiés dans l'échantillon de PF. La caractérisation du profil des Lt a permis de proposer un profil mixte Th1/Th2 causé par l'exposition. L'étude transcriptomique des miARN a mis en évidence une surexpression de miR-124-3p impliqué dans la régulation de plusieurs fonctions au niveau du système immunitaire et de miR-1290 impliqué dans plusieurs types de cancer. Quant à l'influence de l'âge, une surexpression des gènes codant pour les enzymes antioxydantes (NQO1 et HMOX1), une augmentation de la concentration des cytokines (IL-4 et IL-13) ainsi qu'une modification du profil d'expression de certains miARN ont été notées chez les sujets les plus âgés. / Atmospheric fine particulate matter (FP) are able to enter the lungs where some compounds can interact with lung cells and reach the bloodstream . Exposure to FP affects in particular susceptible populations such as the elderly. This thesis is part of a project aiming to identify the effects of FP on human T lymphocytes (LT) while attempting to determine biomarkers related to exposure and to evaluate the variation of the cellular response as a function of age. LT were isolated from blood samples of 91 volunteers belonging to three age groups (20-30, 45-55, 70-85 years) then exposed ex vivo for 72h to 45 µg/µl of FP collected in Dunkirk. The steps of isolation, purification and activation of LT were first optimized. Following the characterization of the sampled population, a homogeneous study population was selected (10 subjects/age class). We have demonstrated an induction of the genes coding for the enzymes involved in the metabolic activation of PAH identified in the PF sample. Characterization of the LT profile made it possible to propose a mixed th1/th2 profile cause by the exposure. Teh transcriptomic study of miRNAs revealed an overexpression of miR-124-3p involved in the regulation of several functions in the immune system and miR-1290 involved in several types of cancer. As for the influence of age, overexpression of the genes coding for the antioxidant enzymes (NQO1 and HMOX1), an increase in the concentration of cytokines (IL-4 and IL-13) as well as a modification of the expression profile of some miRNAs were noted on the elderly.

La pollution atmosphérique particulaire représente un facteur de risque potentiel même à de faibles concentrations. Quelle que soit leur composition, les nanoparticules (NP) sont parmi les plus nocives en raison de leur capacité à atteindre profondément les tissus pulmonaires, la circulation sanguine et les organes. Notre travail constitue une base solide dans la compréhension des effets induits par une sélection de polluants atmosphériques représentatifs, utilisés dans un contexte environnemental réaliste. Nos résultats in vitro fournissent l'évidence d'un effet génotoxique à dominance clastogène lors de l’exposition de cellules à des NP contenant du CeO2, qui d’une part exercent une action mécanique sur le noyau, et d’autre part stimulent la production de O2•- / H2O2 via la NADPH oxydase et la mitochondrie, favorisant la production d’HO•. En présence de 1-Nitropyrène, on observe selon la dose utilisée deux mécanismes génotoxiques successifs, passant d'une dominance aneugène à clastogène, cet effet étant relié à une surproduction de HO• détectable par RPE. L'étude in vivo chez le rat a mis en œuvre un système de génération d'aérosols de NP contenant des pesticides, réalisant une exposition quotidienne et chronique à de faibles doses. Un effet direct sur la fonction hémodynamique myocardique reflétant l'apparition de dommages cellulaires irréversibles a été observée, ainsi que des lésions rénales, hépatiques, et l'installation d'un stress oxydant et d’une inflammation systémiques. Sur le long terme, l'effet des NP modifie les profils lipidiques et favorise la survenue d’une intolérance au glucose. Des modes d'action spécifiques à chaque pesticide employé ont été proposés. / Epidemiological studies have consistently reported that particulate matter in ambient air pollution is associated with increases in cardiopulmonary diseases and mortality. Because they can deeply penetrate lung tissue, reaching blood stream and organs, nanoparticles (NPs) are considered particularly harmful. Here, our foray into the specific mutagenicity and cytotoxicity of NPs focused on manufactured nano-CeO2 (a fuel additive) and NPs known to form in air from a variety of atmospheric toxicants (eg, combustion residues, pesticides). We first revealed a genotoxic effect of nanoCeO2 on human fibroblasts by a clastogenic mechanism following stimulation of the release of O2•-/H2O2 by NADPH oxidase and mitochondria. However, upon exposure of these cells to nM doses of 1-nitropyrene (a combustion byproduct) promotion of DNA damage involving an aneugenic mechanism occurred before a clastogenic effect was seen at µM doses. Second, using a home-made chamber equipped with an aerosol generator, we determined indices of oxidative stress and tissue damage in rats chronically inhaling toxicant NPs for 1-5 months at environmentally relevant doses. Long term exposure, even at low NPs doses, provoked systemic oxidative stress, lipid peroxidation, kidney damage, liver dysfunction, changes in lipid profile and occurrence of disorders of glucose tolerance. Moreover, a strong impairment of hemodynamic performance was evidenced in hearts from NP-exposed rats. By extending literature data of the in vitro toxicity of NPs to the in vivo situation, our study incriminates the nano-sized components of atmospheric particulate matter as a privileged vector of genotoxicity and cardiotoxicity.

Abstract Combustion generated ultrafine particles have been found to be responsible for adverse effects on human health. New emission reduction technologies and fuels will change the composition of particle emissions. It is important to confirm that the new reduction technologies are designed to minimise the adverse health effects. In this doctoral thesis the potential health effects caused by traffic and industrially generated particles were studied using epidemiological, experimental and in silico studies. The effects of short-term changes in PM2.5 on the respiratory health of symptomatic children living near a steel works were studied to investigate whether specific sources of PM2.5 have the possible health effects. The PM2.5 emission sources were identified: long-range transport, a steel works, soil and street dust and a mechanical engineering works. Significant associations were not found between respiratory symptoms and PM2.5 or the sources markers. The deposition of traffic-related particles into the human respiratory system was computed using the lung deposition model. Particle size distribution was measured from diesel- and compressed natural gas (CNG)-fuelled busses and an off-road diesel engine under different combustion situations. The majority of the measured traffic-related particle numbers reach the alveolar region of the lungs. There were differences in the deposition of particles when different catalysts, engines or fuels were used. CNG or a diesel particulate filter (DPF) significantly reduced lung exposure to particles. Also physical activity, age and gender affected the deposition of particles. The diesel particles comprised compounds (carcinogenic PAHs, transition metals), which may have the ability to generate reactive oxygen. This study provides new knowledge how of the emission abatement technologies and fuels affects particle number and their composition, as well health hazards. Cleaner technology (CNG, DPF), emits significantly fewer particles in numbers, especially large particles, but they emit high amounts of small-size particles, which penetrate most easily to the deepest parts of the lungs. In addition, particles from engines with DPF include the largest variety of transition metals and other hazardous compounds compared to combustion systems having different emission after-treatment units. / Tiivistelmä Palamisprosesseista peräisin olevien ultrapienten hiukkasten on todettu olevan haitallisia ihmisen terveydelle. Uudet pako- ja savukaasujen puhdistusteknologiat ja polttoaineet vaikuttavat hiukkaspäästöihin ja niiden koostumukseen. Uusien menetelmien käytön tulee vähentää hiukkasten mahdollisia terveyshaittoja. Tässä väitöskirjassa tutkittiin liikenteestä ja teollisuudesta peräisin olevien hiukkasten mahdollisia terveyshaittoja käyttäen epidemiologista, kokeellista ja in silico- menetelmiä. Työssä tutkittiin PM2.5-hiukkasten lyhytaikaisvaihtelun yhteyttä terästehtaan läheisyydessä asuvien hengitystieoireisten lasten terveyteen ja päästölähteiden yhteyttä mahdollisiin terveysvaikutuksiin. Merkittäviä PM2.5-päästölähteitä olivat kaukokulkeuma, terästehdas, maaperä ja tiepöly sekä konepaja. Tutkimuksessa ei havaittu lasten hengitystieoireiden ja PM2.5:n tai päästölähteiden merkkiaineiden välillä merkittävää yhteyttä. Liikenneperäisten hiukkasten kulkeutumista ihmisen hengitysteihin tutkittiin keuhkodepositiomallilla. Diesel- ja maakaasukäyttöisten (CNG) bussien ja dieselkäyttöisen työkoneen hiukkaskokojakaumat mitattiin eri palamisolosuhteissa. Suurin osa mitatuista hiukkaslukumääristä kulkeutui keuhkojen alveolaaritasolle. Erilaisten katalysaattorien, moottoreiden tai polttoaineiden käytön seurauksena hiukkasten lukumääräpitoisuudet vaihtelivat ja siten hiukkasten kulkeutumisessa hengitysteihin oli eroja. CNG:n tai hiukkassuodattimen (DPF) käyttö vähensi merkittävästi hiukkaslukumääriä ja keuhkojen altistumista hiukkasille. Myös liikunta, ikä ja sukupuoli vaikuttivat hengitysteihin kulkeutuvien hiukkasten määriin. Dieselhiukkaset sisälsivät yhdisteitä (karsinogeeniset PAH:t, siirtymämetallit), jotka tuottavat hengitysteissä reaktiivisia happiradikaaleja. Tämä tutkimus antaa uutta tietoa päästövähennysmenetelmien ja polttoaineiden vaikutuksista hiukkasten lukumäärään ja koostumukseen sekä hiukkasten terveyshaitoihin. Puhtaamman teknologian käyttö (CNG, DPF) vähentää huomattavasti pakokaasun hiukkasten lukumäärää, etenkin suurten hiukkasten, mutta tuottaa silti suuria määriä pieniä hiukkasia, jotka kulkeutuvat helpommin keuhkojen syvimpiin osiin. Lisäksi moottoreiden hiukkaspäästöt käytettäessä hiukkassuodatinta, sisälsivät enemmän erilaisia siirtymämetalleja ja muita haitallisia aineita verrattuna polttoon, jossa käytettiin muita päästöjen jälkikäsittelymenetelmiä.