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International audience; Objectives: To investigate the association between exposure to unintentionally emitted carbonaceous nanoscale particles (NPs) and small for gestational age (SGA), as well as head circumference (HC) at birth and at two years of age.Methods: Mothers from the French Longitudinal Study of Children (Elfe cohort) who worked during pregnancy were selected for our study. Data collected at birth and during follow-up (up to two years) were used. The probability and frequency of maternal occupational exposure to unintentionally emitted carbonaceous NPs was estimated using a job exposure matrix (MatPUF). Multivariate logistic regression, linear regression, and mixed models were applied to estimate any associations. Analyses were carried out depending on whether mothers stopped working during the first, second, or third trimester of pregnancy.Results: Maternal occupational exposure to unintentionally emitted carbonaceous NPs was associated with SGA in the overall study population by multivariate analysis (ORa = 1.80, 95% CI: 1.29, 2.46), as well as in sub-groups of mothers who stopped working during the second (ORa = 1.84, 95% CI: 1.13, 3.02) or third (ORa = 1.80, 95% CI: 1.10, 2.95) trimesters. There were no significant associations with HC at birth or two years of age.Conclusions: We found a significant association between occupational exposure to carbonaceous NPs and SGA, with the effect depending on the period of exposure during pregnancy. These results should encourage further studies concerning the adverse effects of exposure to carbonaceous NPs on the development of offspring.

Objective: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. Methods: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema &lt, 25%, moderate: between 25 and 50% and severe: &gt, 50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. Results: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02–1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. Conclusion: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos.

Introduction Les Resultats de l’etude NLST aux Etats-Unis et de l’etude NELSON en Europe ont ouvert le debat sur l’opportunite d’un depistage du cancer broncho-pulmonaire (CBP) chez des patients exposes a des carcinogenes respiratoires [1] , [2] . L’objectif de cette analyse est d’evaluer l’impact medico-economique, en France, de la mise en place d’un programme de depistage du CBP dans une cohorte de sujets exposes a l’amiante. Methodes L’analyse est basee sur une modelisation MCMC (Monte Carlo Markok Chain) permettant d’etablir le rapport cout utilite de la mise en place d’un depistage annuel du CBP par tomodensitometrie thoracique chez des sujets fumeurs et exposes fortement a l’amiante. Les donnees utilisees dans la modelisation sont l’incidence de CBP dans la cohorte francaise ARDCO (cohorte multiregionale de sujets exposes a l’amiante avec suivi longitudinal depuis 2002), et leurs consommations de soins, les parametres d’intervention sont issus de l’etude NLST. Les donnees d’utilites et de couts de prise en charge des CBP diagnostiques sont issues de la litterature. Une analyse de sensibilite a permis d’evaluer differentes strategies de depistage selon l’intervalle entre les scanners et la population cible. Resultats La mise en place d’un depistage annuel par TDM thoracique chez les sujets fumeurs et exposes fortement a l’amiante permet un gain de QALY de 0.041 par personne [IC 95 % 0.028–0.052] pour un cout de 6208 € par personne [IC 95 % 4536€–7904€], soit un ratio cout-utilite differentiel de 93 020 €/QALY [IC 95 % 51 898€–170 492€]. Lorsque le depistage repose sur un scanner tous les 2 ans, le rapport cout-utilite est plus favorable: 40 938 €/QALY [IC 95 % 22 440€–65 364€]. Conclusion Au regard des seuils habituels pour une intervention de sante, un depistage du CBP par TDM thoracique tous les 2 ans est acceptable et preferable a un depistage annuel dans cette population.

International audience; Objectives: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.Methods: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2,029 lung cancer cases and 2,591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.Results: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR=1.51; 95% CI: 1.22-1.86 and brain tumors (OR=1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR=0.78; 95% CI: 0.46-1.33).Conclusion: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

Aims Unintentional nanoscale particles (UNP) are generated from usual work processes and thus exist since a long time and are more prevalent than the manufactured nanoscale particles. The objective of this study was to develop a job-exposure matrix, a useful tool to estimate prevalence of occupational exposure to UNP for epidemiologic studies. . Methods Work-processes generating UNP and their associated chemical families have been identified through an extensive literature review and the knowledge of an expert’s panel in various domain such as industrial hygiene, toxicology, atmospheric physics and chemistry, epidemiology… These processes were associated to occupations extracted from the ISCO classification edition 1968. A probability and a frequency were assessed for each specific combination “occupation × work-process”. When an occupation was related to several work-processes, the final exposure assessment consisted in the highest probability of exposure and a weighted-frequency of exposure combining assessments from each related work-process. Exposure assessment for some specific occupations could differ according to industries and historical periods. Due to the few available measurement data, intensity could not be assessed at that time. Results Over 50 work-processes generating UNP have been identified and were related with seven UNP chemical families: metal, mineral, carbon, wood, polymer, polycyclic aromatic hydrocarbon (PAH) and other organic. A little less than 50% occupational ISCO codes were unexposed, and 9%, 13% and 31% were possibly, probably and certainly exposed, respectively. Most of occupations were exposed to carbonaceous, PAHs UNP and then to metallic and mineral UNP. Conclusions These results suggest that occupational exposure to UNP might be important at the workplace and might concern a wide variety of workers. In order to assess intensity of exposure, we are currently organising measurement campaigns in French and Canadian workplaces (ExproPNano program).

Contexte Dans les suites de la conference de consensus de 1999 sur le suivi medical des personnes ayant ete exposees a l’amiante, un programme experimental multiregional a ete mis en place, avec constitution de la cohorte asbestos-related diseases cohort (ARDCO). Objectif Ce travail etudie l’association entre plaques pleurales identifiees sur examen tomodensitometrique (TDM) du thorax et risque de mesotheliome ou de deces par cancer du poumon. Methodes Entre 2003 et 2005, des sujets retraites, anterieurement exposes a l’amiante et relevant du RGSS ont ete invites a participer a un programme de depistage dans les regions Aquitaine, Haute et Basse Normandie et Rhone-Alpes. Un index d’exposition cumule (IEC) a l’amiante a ete calcule pour chaque individu a partir d’un questionnaire professionnel standardise. Les examens TDM thoraciques ont ete relus par des experts radiologues, afin de determiner notamment l’existence d’anomalies pleurales liees a l’amiante (donnees disponibles chez plus de 5000 sujets). Les cas de mesotheliome incidents ont ete reperes a partir des demandes de prise en charge en ALD ou en maladie professionnelle (MP) aupres de la Securite sociale, avec sollicitation du College des anatomopathologistes specialises (MESOPATH) pour confirmer le diagnostic. Pour l’etude des CBP, une etude de mortalite a ete realisee avec obtention des causes de deces jusqu’au 31-12-2010 aupres du service CepiDc de l’Inserm. L’analyse statistique s’appuie sur une analyse de survie basee sur un modele de Cox, l’âge etant la variable principale. Resultats Chez les hommes, l’etude d’incidence (donnees ALD-MP) a retrouve une association significative entre la presence de plaques pleurales sur le TDM et le risque de developper un mesotheliome (hazard ratio [HR] ajuste sur l’IEC a l’amiante et la latence : 6,8 [IC 95 % : 2,2–21,4] pour les plaques pleurales typiques). L’etude de mortalite a identifie une association significative entre plaques pleurales et mortalite par cancer du poumon (HR ajuste sur le tabac et l’IEC a l’amiante : 2,41 [IC 95 % : 1,21–4,85]). Conclusion La presence de plaques pleurales apparait etre un facteur de risque independant pour la survenue du mesotheliome pleural et pour le risque de deces par cancer du poumon chez des sujets ayant ete exposes a l’amiante.

Introduction Parmi les particules nanometriques (diametre nominal inferieur a 100 nm), on distingue les particules manufacturees, generees a des fins commerciales, de celles non intentionnellement emises, d’origine naturelle ou produites lors d’emissions secondaires de procedes technologiques courants (moteurs thermiques…). Les donnees toxicologiques ont montre une relation probable entre particules nanometriques et cancer [1] . De meme, les donnees epidemiologiques ont permis de classer les particules diesel et celles de la pollution atmospherique (fraction elevee en nombre de particules nanometrique), comme cancerogenes certains pour l’homme [2] , [3] . Enfin, la capacite des particules nanometriques a traverser les differentes barrieres biologiques et notamment la barriere hemato-encephalique conduit a s’interroger sur un possible role dans la survenue de tumeurs du systeme nerveux central. L’objectif de notre etude etait d’analyser l’association entre exposition professionnelle aux particules nanometriques non intentionnellement generees et survenue de cancer (poumon, mesotheliome pleural et tumeurs du systeme nerveux central). Methode Les donnees de trois etudes cas–temoins francaises (ICARE, PNSM et CERENAT) ont ete analysees. A partir de l’histoire professionnelle complete des sujets, l’exposition professionnelle aux particules nanometriques a ete evaluee par une matrice emplois–exposition (MatPUF) permettant d’attribuer a chaque emploi une probabilite et une frequence d’exposition [4] . Pour chaque sujet, la duree totale d’exposition (en annee) a ete calculee. Les rapports de cotes et intervalles de confiance a 95 % ont ete estimes par regressions logistiques ajustes sur les principaux facteurs de risque des cancers etudies. Resultats Des associations significatives entre particules nanometriques et cancer du poumon d’une part (RC = 1,3 ; IC 95 % = 1,0–1,7) et tumeurs du systeme nerveux central d’autre part ont ete observees (RC = 1,7 ; IC 95 % = 1,1–2,4) chez les hommes. La prise en compte de la duree n’a pas permis de montrer de relation dose-effet. Par ailleurs, aucun lien n’a ete mis en evidence avec le mesotheliome pleural (RC = 0,9 ; IC 95 % = 0,5–1,4). Conclusion Ces premiers resultats incitent a renforcer la connaissance sur les expositions (notamment par des mesures de differents postes de travail, et differentes tâches) et a developper des etudes epidemiologiques integrant des parametres d’exposition plus precis, comme l’intensite dans la matrice MatPUF.

Introduction Les particules nanometriques sont couramment definies comme ayant un diametre nominal inferieur a 100 nm. Il est possible de distinguer les particules manufacturees, generees a des fins commerciales, de celles non intentionnellement emises et qui peuvent etre d’origine naturelle (erosion des sols…), ou anthropique lors des emissions secondaires de procedes technologiques courants tels que les moteurs thermiques. Les donnees toxicologiques ont montre une relation probable entre particules nanometriques et cancer. De meme, les donnees epidemiologiques ont permis de classer les particules diesel et les particules de la pollution atmospherique comme cancerogenes certains pour l’homme (independamment de leur taille). Enfin, la capacite des particules nanometriques a traverser les differentes barrieres biologiques et notamment, la barriere hemato-encephalique a fait emerger l’hypothese d’un possible lien avec la survenue de tumeurs du systeme nerveux central. L’objectif de ces analyses est d’etudier l’association entre l’exposition professionnelle aux particules nanometriques non-intentionnellement generees au travers de differents procedes de travail et la survenue de tumeurs du systeme nerveux central. Methode Les donnees de l’etude cas-temoins CERENAT incluant 596 cas de tumeurs du systeme nerveux central et 1192 temoins, entre 2004 et 2006, dans 4 departements francais, ont ete analysees. A partir de l’histoire professionnelle complete des sujets, l’exposition professionnelle aux particules nanometriques a ete evaluee par le biais d’une matrice emplois-exposition. Pour chaque sujet, la duree totale d’exposition ainsi qu’un score d’exposition ont ete calcules. Les rapports de cotes et intervalles de confiance a 95 % ont ete estimes par une regression logistique conditionnelle. Resultats Une association significative entre exposition professionnelle aux particules nanometriques et tumeurs du systeme nerveux central a ete observee chez les hommes (RC = 1,5 ; IC 95 % = 1,1–2,2). Cet exces de risque semble etre plus particulierement lie a de fortes expositions (RC = 1,9 ; IC 95 % = 1,2–2,8 pour des durees totales d’exposition superieures a 30 ans) ainsi qu’aux particules carbonees (RC = 1,5 ; IC 95 % = 1,1–2,3) et HAP (RC = 1,6 ; IC 95 % = 1,1–2,4). Conclusion Meme si ces premieres analyses doivent etre confirmees, notamment en prenant en compte l’intensite des expositions (en cours de determination dans une nouvelle version de la matrice), ces resultats incitent au developpement de recherches epidemiologiques sur ces nuisances ainsi qu’a une reflexion sur les expositions et sur les mesures de prevention en milieu de travail.

International audience; Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection.