Les troubles musculo-squelettiques (TMS) sont la principale cause d’absentéisme au travail. Ils représentent un coût économique important, mais ils ont aussi de graves conséquences au niveau individuel – douleurs persistantes, limitations fonctionnelles ou perte d’emploi. De nombreuses expositions professionnelles ont déjà été mises en évidence pour expliquer la présence de ces symptômes, mais certaines relations restent encore à confirmer.L’objectif de ce travail de thèse était d’étudier l’association entre les facteurs professionnels, en particulier les facteurs physiques, et les TMS au niveau des coudes et des genoux. Les TMS au niveau des coudes ont été étudiés à travers la prévalence des symptômes aux coudes et des épicondylites, et l’incidence des épicondylites. Les douleurs aux genoux ont été étudiées à travers l’incidence des douleurs de courte ou de longue durée. Ce travail a nécessité l’utilisation de méthodologies spécifiques, en particulier les diagrammes causaux et les méthodes de gestion des données manquantes qui seront explicitées dans une partie théorique. La population dans ce travail de thèse était une cohorte de 3 710 sujets représentatifs des actifs des Pays de la Loire. Ils ont été recrutés entre 2002 et 2005 et ont été suivis entre 2007 et 2010. A chaque phase, un questionnaire sur les conditions de travail a été rempli par les participants et un examen clinique qui évaluait la présence de troubles musculo-squelettiques a été réalisé par des médecins du travail volontaires. En conclusion, les facteurs professionnels mis en évidence étaient globalement des facteurs de mouvements répétitifs impliquant les articulations étudiées (torsion des poignets et flexion/extension des coudes ou le fait de s’agenouiller). Le travail en force (manipulation de charges, efforts physiques importants) et les tâches répétitives ont également été mis en évidence comme prédicteurs de TMS ultérieurs / Musculoskeletal disorders (MSDs) are a leading cause of absenteeism from work. In addition to their major economic impact, musculoskeletal disorders have important consequences on individuals with the persistence of pain, disability and potential job loss. Many occupational exposures were highlighted to explain these symptoms, but certain relationships between occupational exposures and MSDs should be examined further.The aim of this thesis is to investigate the association between occupational exposures, especially biomechanical exposures, and elbow or knee MSDs. The elbow MSDs are studied with the prevalence of symptoms and lateral epicondylitis, and the incidence of lateral epicondylitis. The incidence of knee pain is examined according to its duration.The methodologies and theories appropriate to this type of work is briefly presented - a section focuses on the causal diagrams and methods of handling missing data.The population used is a cohort of 3710 subjects representative of the French workforce. Subjects were selected from workers undergoing a mandatory annual health examination between 2002 and 2005 and were followed between 2007 and 2010. For each phase of the study, a self-administered questionnaire on working conditions was completed and a clinical examination was performed in order to evaluate the presence of musculoskeletal disorders. In conclusion, repetitive movements involving the joints studied such as wrist-twisting, flexion/extension of the elbows or kneeling are associated with MSDs. The notion of force, such as load handling and physical exertion, and the notion of repetitive tasks are also identified as predictors of subsequent MSDs

Orientador: Eduardo Luiz Bagagli / Resumo: Infecções fúngicas causadas por leveduras constituem um dos maiores problemas em pacientes hospitalizados em todo o mundo e têm se tornado uma importante causa de morbidade e mortalidade. Embora Candida albicans seja a espécie mais frequentemente isolada e sua forma de infecção ocorra geralmente por translocação endógena, tem-se observado um aumento das espécies não-albicans, com destaque para o complexo C. parapsilosis, cuja principal forma de infecção é exógena, provavelmente pelas mãos dos profissionais de saúde. Este trabalho propôs estudar os aspectos microbiológicos e ambientais das candidemias, com especial atenção para o complexo Candida parapsilosis, no hospital terciário HC/FMB/UNESP, Botucatu, utilizando-se de métodos moleculares, busca ativa dos agentes no ambiente hospitalar (ar, superfícies e mãos de profissionais de saúde), bem como determinar os fatores de virulência e susceptibilidade aos antifúngicos destas espécies e associação com o desfecho clínico. Os isolados clínicos (obtidos de hemoculturas, período 2007-2015) e ambientais (período 2014-2015) de C. parapsilosis sensu lato foram identificados pelo meio CHROMagar Candida, Vitek-2, sequenciamento do rDNA e perfis dos inteins VMA e ThrRS. Fatores de virulência (produção de proteinase, fosfolipase e biofilme) e perfis de susceptibilidade aos antifúngicos anfotericina B, fluconazol, voriconazol, caspofungina e micafungina foram estimados, e dados clínicos obtidos junto aos prontuários dos pacientes. Dentre ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Fungal infections caused by yeasts are serious problems in hospitalized patients around the globe and have become a major cause of morbidity and mortality. Although Candida albicans is the most frequently isolated species and its infection usually occurs by endogenous translocation, an increase of non-albicans species has been observed, with emphasys for the C. parapsilosis complex, whose main route of infection is exogenous, probably by the hands of health professionals. This work proposes to study the microbiological and environmental aspects of candidemia, with special attention to the C. parapsilosis complex, in a public tertiary hospital HC/FMB/UNESP, in Botucatu, using the molecular methods, active search of agents in the hospital environment (air, surfaces and hands of health professionals), as well as to determine the virulence factors and susceptibility to the antifungals of these species and correlate with the patient clinical outcomes. The clinical isolates (obtained of the blood cultures, 2007-2015 period) and environmental (2014-2015 period) of the C. parapsilosis sensu lato were identified by CHROMagar Candida medium, Vitek-2, rDNA sequencing and VMA and ThrRS inteins profiles. Virulence factors (production of proteinase, phospholypase and biofilm) and profiles of susceptibility to antifungals amphotericin B, fluconazole, voriconazole, caspofungin and micafungin were estimated, and the clinical data were obtained from patient’s records. Among the clinical isolat... (Complete abstract click electronic access below) / Doutor

Submitted by Alexandre Gomes (aludolf@gmail.com) on 2017-01-30T17:16:34Z No. of bitstreams: 1 FUNDOS MULTIMERCADOS BRASILEIROS CRIAM VALOR UMA AVALIACAO DOS ALFAS.pdf: 3747366 bytes, checksum: 91e4b622130ab4ac64d4ffc168ba2458 (MD5) / Approved for entry into archive by Renata de Souza Nascimento (renata.souza@fgv.br) on 2017-01-30T17:18:27Z (GMT) No. of bitstreams: 1 FUNDOS MULTIMERCADOS BRASILEIROS CRIAM VALOR UMA AVALIACAO DOS ALFAS.pdf: 3747366 bytes, checksum: 91e4b622130ab4ac64d4ffc168ba2458 (MD5) / Made available in DSpace on 2017-01-30T17:21:28Z (GMT). No. of bitstreams: 1 FUNDOS MULTIMERCADOS BRASILEIROS CRIAM VALOR UMA AVALIACAO DOS ALFAS.pdf: 3747366 bytes, checksum: 91e4b622130ab4ac64d4ffc168ba2458 (MD5) Previous issue date: 2016-12-16 / This work examines the alpha generation of the Brazilian multimarket fund industry, taking in account fund specific characteristics, fund strategies, investor segment during different economic conditions. The employed dataset represents 1,568 multistrategy funds from 328 different managers within a 10-year timeframe from Dec-2005 to Dec-2015. The proposed model utilizes a stepwise automatic feature selection method, similar to other authors such as Stafylas, Anderson e Uddin (2015), where features are selected from a regressor candidates list that contemplates: equity factors, interest rate factors, credit factors, currency factors and commodities factors. The results found shows that at a 5% level there is positive alpha generation, that is, Brazilian multistrategy funds on average have delivered extraordinary returns on the whole sample and at the more benign market environments. During less benign market environment multistrategy funds does not deliver alpha that is statistically distinguishable from zero and sub-strategy segmentation points to different risk exposures dynamics during different market conditions. / Esse trabalho analisa a geração de alfa da indústria brasileira de fundos multimercado, levando em consideração características específicas, estratégias de investimento e segmento de investidor durante diferentes condições econômicas. A amostra utilizada compreende 1.568 fundos de 328 gestores distintos, observados em granularidade mensal durante período de 10 anos, de dez-2005 a dez-2015. O método empírico utilizado faz uso de processo de seleção automática de regressores via stepwise, modelagem implementada por autores como Stafylas, Anderson e Uddin (2015), selecionados de uma lista prévia de candidatos a regressores amparados na literatura e contemplando fatores de ações, fatores de juros, fatores de risco de crédito, fatores de moedas e fatores de commodities. Os resultados obtidos mostram que a 5% existe geração de alfa positivo na categoria de fundos, isto é, os gestores de fundos multimercado têm capacidade de gerar, na média, retornos anormais na administração dos recursos dos investidores ao longo do tempo, tanto na amostra total quanto nos períodos econômicos mais benignos, contudo não apresentam retornos extraordinários estatisticamente diferentes de zero durante períodos econômicos menos benignos. Além disso, os fundos também apresentam diferenças sensíveis na composição dos retornos quando avaliados por sub-estratégias e em diferentes condições de mercado.

Les tumeurs germinales du testicule (TGCT) sont la forme de cancer la plus fréquente chez les hommes jeunes (15-39 ans). Un rôle de l'environnement au moment de la période prénatale est suspecté, mais aucune étiologie claire ne semble émerger. Cette thèse avait pour but de développer une nouvelle approche épidémiologique pour étudier l'impact des expositions prénatales aux pesticides sur le risque de TGCT. Par une revue de la littérature, nous avons tout d'abord montré le manque d'études sur les expositions prénatales et le besoin de méthodes fiables pour évaluer l'exposition environnementale aux pesticides. Ensuite, par une campagne de mesures domestiques dans 239 foyers, nous avons identifié les déterminants environnementaux de l'exposition aux pesticides agricoles. La surface des cultures dans un rayon de 500m (vergers) ou 1000m (céréales/vignes), le vent et les barrières végétales ont été identifiés comme déterminants de l'exposition. La bonne efficacité de notre lingette en cellulose a été testée en laboratoire. Nos résultats montrent également l'importance des utilisations domestiques de pesticides sur la contamination des foyers. Enfin, à travers une étude cas témoins pilote, nous avons confirmé notre capacité à recruter des sujets et leurs mères, ainsi que les informations requises pour évaluer les expositions jusque dans les années 70. Pour conclure, nos résultats ont permis le développement d'une étude cas-témoins nationale (projet TESTIS) pour étudier l'impact des expositions prénatales aux pesticides sur le risque de TGCT. Ce projet a été financé et est en cours de réalisation. Cette thèse sert également de base à plusieurs autres projets multidisciplinaires / Testicular germ cell tumors (TGCT) are the most common cancers in men aged 15–39 years. Environmental exposures occurring in the prenatal period are suspected to play a role, but no clear associations with TGCT risk are known. This thesis aimed to develop an epidemiological approach to study the impact of prenatal exposures to pesticides on the TGCT risk. First, through a systematic literature review, we identified a gap in knowledge regarding prenatal exposures, as well as the need for more reliable assessment of environmental pesticide exposures. Second, through a survey of indoor dust sampling in 239 households, we identified the environmental determinants of agricultural pesticide exposure to develop a metric to assess environmental pesticide exposures using a geographical information system. Crop acreage within 500m (orchards) or 1000m (cereals/vineyards), wind, and vegetative barriers were identified as determinants of the indoor contamination. The overall good efficiency of our cellulose wipe was assessed through laboratory experiments. Our results also suggested domestic pesticide use as a major source of households’ pesticide exposure. Third, through a case-control pilot study we tested different approach to recruit young men and their mothers, and we confirmed our ability to collect information about their exposures, and to map precisely their addresses until the 1970’s. Our findings lead to the development of a national case-control study (TESTIS project) aiming to assess the impact of prenatal pesticides exposures on the TGCT risk. This project has been funded and is currently on-going. Our research also serves as basis for further multidisciplinary projects

The thesis is based on the need of workplaces, where ionizing radiation sources are used, to implement a new legislation in the field of the Atomic Act effective since 1st January 2017. The thesis is focusing specifically on Radiation accidental exposures and radiation emergency on selected radiotherapeutic departments with linear particle accelerator. The theoretical part deals with definitions and categorization of radiation accidents and radiation emergency, relevant legal requirements and related work documentation related to this issue. The practical part deals with the evaluation of specific documents processed at two radiotherapeutic departments, the outcome of which is a proposal for their revision, which in agreement with the requirements of the new legislation and submitted for SÚJB´s approval. Primarily, for this purpose, it is a part of the practical part to create data file of actual radiation accidents and radiation emergencies in two specific workplaces and to analyze the causes of their occurrence. An interesting element is the choice of workplaces with a different producer of a linear accelerator, where are only two companies on the market. This choice was intend to determine whether the root causes of radiology accidents can have a causal link in relation to the technology in question of SW or accessories of the producer. The aim of the analysis is, in any case, awareness, prevention and iterative removal of the causes of accidents and the adoption of such measures in order to avoid any recurrence of events already occurred. All precautionary and follow-up measures, including responsibilities and competences, must be documented in the documentation of departments, with each holder of the resource authorization being required to keep this documentation in agreement with practice and current legislation. The thesis contributes to the detection of the causes of the accidents and the revision of the related documentation in order to be in agreement with the actual situation in the given depratments.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Selenium (Se) is an essential trace element for man and is known for its role in regulating growth and development of the fetus and newborn. Furthermore, Se is a micronutrient required for normal spermatogenesis and, therefore, essential for normal male reproductive function. However, it is well known that this element, depending of dose, can be highly toxic to several species of animals. Diphenyl diselenide [(PhSe)2] is a Se-compound widely used as intermediate in organic synthesis, as a consequence, the risk of human exposure to this chemical at the workplace may increase. Several studies demonstrated that (PhSe)2 is an organoselenium compound with potential therapeutic use. The present study evaluates the effects of single maternal subcutaneous injection of 50 and 100 mg/kg (PhSe)2 at gestational days (GD) 6, 10 or 17 in Wistar rats (article 1). The highest dose of (PhSe)2 was also administered at GD7-12. External and internal fetal soft-tissue examination was performed at GD20. No mortality was observed in fetuses or dams at any (PhSe)2 treatment. Neither did exposure to (PhSe)2 cause significant changes to fetal body weight, organ weight, or fetal size when dministered at GD6-8, 10-12 or 17. Exposure to 100 mg/kg (PhSe)2 at GD 9 produced significant changes in fetal biometry (crown-rump (CR) length) and body weight. No increase in the proportion of fetuses with external visible abnormalities was observed in groups exposed to (PhSe)2. Skeletal anomalies were observed in fetuses in the GD 9-11 treatment groups and included incomplete ossification of cranial bones, misshapen and incomplete ossification of sternebrae, reduced sternebrae number, wavy and extra ribs, incomplete ossification of fore and hindpaw bones and incomplete ossification of sacral and caudal bones. We conclude that maternal administration of (PhSe)2 during GD 7-12 led to increased incidences of these skeletal variations or anomalies, but did not cause externally visible malformations in rat fetuses. Another focus of this study was the evaluation of the effect of paternal exposure to (PhSe)2 on the development of progeny of Wistar male rats (article 2). Male rats were exposed to (PhSe)2 subcutaneously for 4 weeks (wk) at the dose of 5.0 mg/kg and 8 weeks at the dose of 2.5 mg/kg, prior to mating with unexposed females. No lethality was noted in any group. At term of exposure period, 4-wk-exposed male rats presented significant decrease in the body weight. Sex organ weights were similar in (PhSe)2-exposed and control male groups. The number of implantation sites in females mated with males exposed to (PhSe)2 for 8-wk was significantly higher than those of the respective control group. Male exposure to (PhSe)2, administered for 4- and 8-wk, did not change fetal body weight. Gross examination of fetuses from 4- and 8-wk-exposed groups did not reveal the appearance of external anomalies. Examination of live fetuses for ossification centers did not show any significant difference between groups. No increase in the incidence of skeletal anomalies was observed in fetuses obtained from females impregnated with (PhSe)2-exposed males. The current study indicated that (PhSe)2 given sub-chronically (4 or 8 weeks) to male rats had no adverse effects on their progeny. On the basis of results mentioned above, it is possible conclude that (PhSe)2 is a compound with low developmental toxicity, since adverse effects observed were only manifested at a high level dose. Of particular importance, (PhSe)2 possess its pharmacological properties at doses lower than these tested here. / O selênio (Se) é um elemento traço essencial para humanos e desempenha uma importante função durante a gestação, regulando o crescimento e desenvolvimento de fetos e recém-nascidos. Além disso, o Se é um micronutriente requerido para o processo da espermatogênese e, portanto, essencial para a função reprodutiva em machos. Entretanto, o elemento Se, dependendo da dose, pode ser tóxico para diversas espécies de animais. O disseleneto de difenila [(ØSe)2] é um composto de Se amplamente utilizado como intermediário em reações de síntese orgânica, o que aumenta o risco de intoxicação por exposição ocupacional a este composto. Existem diversos estudos demonstrando que o (ØSe)2 possui propriedades farmacológicas. O presente estudo avaliou os efeitos da administração subcutânea, única, de (ØSe)2 nas doses de 50 ou 100 mg/kg no 6°, 10° ou 17° dia da gestação de ratas Wistar (artigo 1). Os estudos com a maior dose de (ØSe)2 (100 mg/kg) foram estendidos a outros dias da gestação (7° ao 12°). No 20° dia de gestação foi realizada uma laparotomia para a retirada dos fetos e a observação do aparecimento de malformações morfológicas externas e esqueléticas. Não foram observadas mortes maternas e fetais nos grupos expostos ao (ØSe)2. A exposição ao (∅Se)2 não causou alterações significativas nos parâmetros de desenvolvimento avaliados (peso e comprimento fetal), com exceção da exposição a 100 mg/kg de (∅Se)2 no 9° dia de gestação, a qual produziu mudanças significativas na biometria fetal: diminuição do comprimento longitudinal e do peso corporal do feto. Não foi observado um aumento significativo no aparecimento de malformações fetais nos grupos expostos ao (∅Se)2. A exposição ao (∅Se)2 aumentou a incidência de alterações na ossificação do esqueleto dos fetos, principalmente nos grupos tratados no 9°, 10° e 11° dia de gestação sem afetar a sobrevivência dos mesmos. As alterações observadas incluem: ossificação incompleta dos ossos do crânio, das vértebras sacrais e caudais e dos ossos das patas anteriores e posteriores. Além disso, foram observadas alterações nas esternebras das quais, destacam-se: malformação, número reduzido e incompleta ossificação. Um número extra de costelas e costelas onduladas também foi observado. Portanto, com base nos resultados encontrados, concluímos que a exposição materna ao (ØSe)2 leva ao aumento na incidência de alterações esqueléticas nos fetos, sem causar o aparecimento de malformações externas visíveis e sem afetar a sobrevivência dos mesmos. Outro foco deste estudo foi avaliar o grau de toxicidade da exposição sub-crônica ao (ØSe)2 sobre o desenvolvimento da prole de ratos Wistar (artigo 2). Os ratos foram expostos ao composto pela via subcutânea por um período de 4 (na dose de 5,0 mg/kg) ou 8 semanas (2,5 mg/kg) antes do período de acasalamento. Não foram observadas mortes em nenhum dos grupos e, ao final do período de exposição, apenas os animais tratados com o composto por um período de 4 semanas apresentaram uma redução significativa do peso corporal. O peso dos órgãos sexuais masculinos (testículos e epidídimos) não foi alterado pelo tratamento. Foi observado um aumento significativo no número de sítios de implantações nas fêmeas acasaladas com os machos expostos ao (ØSe)2 por um período de 8 semanas. Em relação aos parâmetros fetais, não foram observadas anomalias externas e nem mudanças no peso em ambos os grupos tratados com o (ØSe)2 (4 ou 8 semanas). Não foram observadas diferenças significativas no desenvolvimento do esqueleto dos fetos expostos a este composto. O presente estudo demonstrou que a exposição sub-crônica (4 ou 8 semanas) ao (ØSe)2 não causou efeitos adversos sobre a prole de ratos Wistar. Tendo em vista os dados obtidos no presente estudo, é possível concluir que o composto (ØSe)2 apresenta baixa toxicidade desenvolvimental, uma vez que os efeitos adversos observados neste estudo se manifestam apenas em uma dose muito alta. É importante salientar que o (ØSe)2 desempenha suas propriedades farmacológicas em doses mais baixas do que as testadas neste trabalho.

Occupational hearing loss resulting from noise exposures encountered in the workplace affects millions of workers and costs hundreds of millions of dollars annually in Workers’ Compensation costs in the United States alone. Some industries have been well studied, and the presence of hazardous noise in the work environment established and documented. The restaurant industry is one in which little current data exists, but in which there may be cause for concern. This work sought to quantify noise exposures for cooks, servers, and dishwashers and to determine whether or not any of these workers are at risk for Noise Induced Hearing Loss. Further, the researchers wanted to know what environmental factors present in the restaurants had the greatest impact on noise exposures for each exposure group. Statistical analysis was conducted on selected factors, and while nearly all were found to have significant effects on noise exposure for servers, only the number of minutes worked explained variance in exposures for cooks and dishwashers when all factors were included in analysis. These two groups are the ones most likely to be overexposed and they typically worked more than 480 minutes on the day the sample was collected. Efforts to control exposure must take these extended shifts into careful account. The study was limited by relatively small sample size, with 124 cooks, 119 servers, and 91 dishwashers employed at nine different restaurants participating. Future efforts to explain and characterize the sources of variation in noise exposure for these three groups should include greater numbers of participants and structure the data in a way that allows the effects of selected factors to be more clearly seen.

Les asthmes en relation avec le travail (ART) incluent l’asthme professionnel (AP), dû à des causes et conditions attribuables à un environnement professionnel particulier, et l’asthme aggravé par le travail (AAT), qui est une forme pré-existante ou coïncidente d’asthme, aggravée par l’environnement professionnel. Le diagnostic des ART constitue un véritable enjeu. Le premier chapitre est une revue de la littérature, mettant en évidence les points discutés et notamment la place éventuelle des marqueurs de l’inflammation. Le deuxième chapitre présente une analyse de données épidémiologiques chez 417 apprentis coiffeurs et boulangers, des filières à risques d’AP. Des modèles mixtes montrent une association entre le degré de sensibilisation à douze allergènes communs et l’hyperréactivité bronchique (HBR) ainsi que les niveaux de FeNO expiré. Ce dernier est plus élevé de 83% (p<0,01) chez les sujets fortement sensibilisés et de 30% chez les sujets faiblement sensibilisés (p<0,01) comparé au groupe des sujets non sensibilisés. Le troisième chapitre relate l’élaboration d’un protocole de recherche (ARPEIGE) visant à acquérir des connaissances cliniques, épidémiologiques et économiques sur les ART, et aux développement et choix des outils et algorithmes décisionnels. L’analyse des questionnaires de repérage montre qu’en visite de routine en médecine du travail, une part non négligeable de salariés déclare des symptômes respiratoires évoquant un asthme actif, dont certains pourraient être en lien avec le travail. Ce protocole met en évidence la difficulté d’effectuer un dépistage des ART par le faible taux de retours des questionnaires approfondis. Malgré l’importance du diagnostic des ART, les stratégies diagnostiques restent discutées. Si les données chez les apprentis ont montré une association entre certains marqueurs de l’inflammation bronchique (FeNO) et des marqueurs d’atopie (tests cutanés), leur place dans le diagnostic clinique de l’asthme reste discutée. Au-delà des stratégies visant au diagnostic individuel, se pose également la question des stratégies diagnostiques utilisables en population professionnelle. Dans l’étude ARPEIGE, un questionnaire de repérage des symptômes fournit des données relatives à la prévalence des symptômes évocateurs d’asthme. Cependant, peu de sujets repérés acceptent de poursuivre les investigations, d’où l’importance de réfléchir à des stratégies qui permettraient un dépistage des ART au-delà de l’étape de repérage. / Work-related asthma (WRA) includes work aggravation of preexisting asthma (WEA) and new-onset asthma induced by occupational exposure (OA). Making an accurate diagnosis of WRA is important, the condition having significant health consequences and substantial socio-economic impacts. The first part is based on a literature review including data on prevalence, risk factors and diagnosis procedures of WRA. The issues in diagnosing WRA are also discussed, as well as the use of airway inflammation markers (FeNO levels and sputum eosinophils). The second part shows an analysis of epidemiological data in 417 apprentices in baking, pastry-cooking and hairdressing, which are populations at risk of OA. Mixed-effect models were applied and showed that the degree of sensitization was related to bronchial hyperresponsiveness (BHR) and FeNO levels. Compared to non-sensitized subjects, FeNO levels were 83% higher (p>0,01) in highly sensitized subjects and 30% higher (p<0,01) in weakly sensitized subjects. The third part describes the protocol of a field study aiming to collect new data on clinical, epidemiological and economical aspects of WRA. It focuses especially on the design of tools and decision algorithms, such as a screening questionnaire, and more advanced questionnaires on control, quality of life, expositions and socio-economic consequences, and a peak-flow journal. Screening results show that a substantial number of workers declare asthma-like respiratory symptoms, some of which being possibly related to work. Despite the importance of WRA diagnosis, diagnostic procedures are still being discussed. Although the apprentice study showed an association between airway inflammation markers (FeNO levels) and atopy markers (prick-tests), their use in the diagnostic procedure is still under discussion. Diagnostic procedures that could be used in populations at work are also subject to think about, in particular in epidemiological study, with the difficulty of differentiating OA from WEA. Thus, in the ARPEIGE study, a screening questionnaire was useful to collect data on asthma-like respiratory symptoms. Nevertheless, few screened workers agreed to go further and fill in the peak flow journal. Similarly, in the literature asthma and COPD screening campaigns using spirometry seemed difficult to implement. There is a lack of strategies that would enable a more accurate screening of WRA.

No description available.

Les éleveurs laitiers-bovins présentent une incidence plus élevée de symptômes respiratoires et de maladies broncho-pulmonaires que la population générale. Un facteur de risque important serait l’exposition professionnelle à divers aéro-contaminants d’origine biologique et chimique. Les déterminants professionnels de ces expositions et les effets biologiques des contaminants inhalés de manière répétée restent cependant mal connus. Dans ce contexte, les travaux réalisés au cours de cette thèse avaient pour objectifs i) de rechercher les déterminants professionnels de l’exposition aux bio-aérosols thoraciques (poussières organiques, endotoxines, bactéries et moisissures), à l’ammoniac et à l’acétaldéhyde, et ii) de caractériser les effets pro-inflammatoires des poussières thoraciques émises lors de la tâche de paillage mécanisé qui est connue pour induire une forte exposition aux bio-aérosols. Pour atteindre ces objectifs, nous avons réalisé une campagne de 112 mesures individuelles répétées dans 29 exploitations laitières d’élevage bovin localisées en Bretagne. Par l’utilisation de modèles multivariés à effets mixtes, nous montrons que l’exposition aux bio-aérosols est majoritairement induite par l’exécution de tâches liées à la distribution de litières et d’aliments (paille, foin, ensilage). L’exposition à l’ammoniac est fortement dépendante du nombre de vaches présentes dans l’exploitation et des temps passés en stabulation et en salle de traite. L’exposition à l’acétaldéhyde est dépendante de la taille de l’exploitation et des tâches liées à la distribution d’ensilage. Nos travaux soulignent également qu’une augmentation de la surface des ouvertures de la stabulation est associée à une réduction significative de l’exposition aux moisissures, à l’ammoniac et à l’acétaldéhyde. Enfin, notre étude montre que les poussières émises lors du paillage mécanisé ont (1) une taille leur permettant de se déposer majoritairement dans les régions trachéo-bronchiques, (2) une composition bactériologique et fongique complexe et (3) in vitro des effets pro-inflammatoires puissants induisant l’expression de TNF-α, d’IL-1β, d’IL-6 et d’IL-8 dans des macrophages humains. Au total, ces travaux de thèse ont permis d’identifier des activités professionnelles et des caractéristiques d’exploitations augmentant significativement les niveaux d’expositions des éleveurs laitiers-bovins à des contaminants chimiques et à des poussières organiques pouvant théoriquement se déposer dans les tissus bronchiques où sont censées se développer différentes maladies broncho-pulmonaires. Les modèles statistiques développés au cours de la thèse permettent dès à présent la reconstitution des expositions des éleveurs et pourront être utilisés dans de futures études épidémiologiques et dans l’élaboration de programmes de prévention. / Dairy farmers have an increased risk of lower airway diseases that is likely related to occupational exposures to airborne contaminants. Nevertheless, occupational determinants of dairy farmers’ exposures remain poorly documented and the biological effects of the contaminants chronically inhaled by farmers need to be fully characterized. In this context, the objectives of this PhD thesis were i) to identify the occupational determinants of exposure to thoracic bio-aerosols (organic dusts, endotoxins, bacteria and moulds), ammonia and acetaldehyde, and ii) to characterize the pro-inflammatory effects of thoracic dusts emitted during the mechanical spreading of straw bedding, a task well-known to generate inhalable dusts. To achieve these goals, we carried out a 112-repeated exposure measurement campaign on 29 dairy farms located in Britany. Using multivariate mixed-effect regression models, we have demonstrated that farmers’ exposures to bio-aerosols were mainly induced by tasks related to bedding material distribution and cow feeding (straw, hay, silage). Exposure levels to ammonia were highly dependent on cow numbers and times spent by the farmers in stable and milking parlour. Acetaldehyde exposure was modulated according to the farm size and times spent to distribute silage. Our work also highlighted that an increase of the area of wall opening significantly reduced exposure to mould, acetaldehyde and ammonia. Finally, our study showed that dusts emitted during mechanical straw spreading have (1) a size small enough to allow them to deposit in the tracheobronchial regions, (2) a complex bacterial and fungal composition, and (3) strong in vitro pro-inflammatory effects that induced TNF-α, IL-1β, IL-6 and IL-8 expression in human macrophages. In conclusion, these results have identified different dairy farm characteristics and occupational tasks that significantly increased the exposure levels to chemical contaminants and thoracic organic dusts. Statistical models built during this research project already allow reconstitution of dairy farmers’ exposure that may of use in future epidemiological studies and to develop new preventive measures.