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Background: Lung cancer screening programs concern smokers at risk for cardiovascular diseases (CVDs) and chronic obstructive pulmonary disease (COPD). The LUMASCAN (LUng Cancer Screening, MArkers and low-dose computed tomography SCANner) study aimed to evaluate the acceptability and feasibility of screening for these 3 diseases in a community population with centralized organization and to determine low-dose computed tomography (CT) markers associated with each disease., Methods: This cohort enrolled participants meeting National Comprehensive Cancer Network criteria (v1.2014) in an organized lung cancer-screening program including low-dose CT scans; spirometry; evaluations of coronary artery calcifications (CACs); and a smoking cessation plan at inclusion, 1, and 2 years; then telephone follow-up. Outcomes were the participation rate and the proportion of participants affected by lung cancer, obstructive lung disease, or CVD events. Logistic-regression models were used to identify radiological factors associated with each disease., Results: Between 2016 and 2019, a total of 302 participants were enrolled: 61% men; median age 58.8 years; 77% active smoker; 11% diabetes; 38% hypertension; and 27% taking lipid-lowering agents. Inclusion, 1-year, and 2-year participation rates were 99%, 81%, 79%, respectively. After a median follow-up of 5.81 years, screenings detected 12 (4%) lung cancer, 9 of 12 via low-dose CT (78% localized) and 3 of 12 during follow-up (all stage IV), 83 (27%) unknown obstructive lung disease, and 131 (43.4%) moderate to severe CACs warranting a cardiology consultation. Preexisting COPD and moderate to severe CACs were associated with major CVD events with odds ratios of 1.98 (95% confident interval [CI] = 1.00 to 3.88) and 3.27 (95% CI = 1.72 to 6.43), respectively., Conclusion: The LUMASCAN study demonstrated the feasibility of combined screening for lung cancer, COPD, and CVD in a community population. Its centralized organization enabled high participation and coordination of healthcare practitioners., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Questions concerning under-reporting of occupational diseases (OD) linked to asbestos exposure are regularly voiced in France. Monitoring of the French multicenter Asbestos-Related Disease Cohort (ARDCO), which ensures post-occupational medical surveillance of subjects having been exposed to asbestos, provides information on (1) the medico-legal steps taken following screening by computed tomography (CT) for benign thoracic diseases, and (2) recognition of OD as a causal factor in malignant diseases., Methods: OD recognition - and possible compensation - was analyzed in July 2021 among 13,289 volunteers in the cohort recruited between 2003 and 2005., Results: Fifteen percent of the subjects in the cohort were found to have at least one recognized asbestos-related OD (78.2% benign pleural disease, 10.3% asbestosis, 14.2% lung cancer, and 6.0% mesothelioma). Only 58% of pleural plaques reported by the radiologist who performed the CT resulted in their recognition as ODs. On a parallel track, 88.7% of the mesotheliomas identified based on French National health insurance data and 46.9% of lung cancers were recognized as ODs., Conclusions: This study confirms the feasibility of a system designed to facilitate recognition, leading to possible compensation, of asbestos-related occupational diseases. The system could be improved by better training of the medical actors involved., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Objective: The aim of this study was to confirm the relationship between several parameters of exposure to asbestos and pleural plaques (PP) using data from a large cohort of retired workers occupationally exposed to asbestos in France., Method: A large screening programme, including high-resolution CT (HRCT) examinations at inclusion and two other HRCT campaigns, was organised from 2003 to 2016 in four regions of France for voluntary, formerly asbestos-exposed workers. Exposure to asbestos has been evaluated by industrial hygienists based on the complete work history. The time since first exposure, the time since last exposure, Cumulative Exposure Index and maximum level of exposure to asbestos, were used in logistic regression using fractional polynomials to model the relationship with PP., Results: The study included 5392 subjects with at least one HRCT available. There was a significant non-linear effect of time since first exposure, time since last exposure and Cumulative Exposure Index to asbestos on the presence of PP. The risk of PP increased with increasing Cumulative Exposure Index to asbestos adjusted for time since first exposure, age and smoking status. Models also show that PP odds rise with increasing time since first exposure adjusted for cumulative index exposure, age and smoking status. PP odds decrease when time since last exposure increases., Conclusion: The study provides new data on the link between asbestos exposure and the presence of PP using fractional polynomials with non-linear relationships for time exposure parameters and asbestos exposure parameters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Asbestos causes cancer and non-cancerous lung and pleural diseases and can also have a negative psychological impact but little is known about its effect on health-related quality of life., Objectives: The aim of this study is to describe the health-related quality of life (HRQoL) of retired men with a history of occupational exposure to asbestos and examine factors linked with low HRQoL., Methods: Retired male workers of the French Asbestos-Related Disease Cohort (ARDCO) completed self-questionnaires that included SF-36v2 and HAD scales, questions about their perception of asbestos (perceived dangers and level of exposure, expectations to fall ill, or knowing someone who is) and their respiratory symptoms. Asbestos exposure was assessed by industrial hygienists. A perceived risk score was created using factorial analysis. Multivariable regressions were performed for all SF-36 subscales., Results: A total of 1266 of 2075 questionnaires (61%) were returned complete and included in analysis. After adjustment for potential confounders, an increase in perceived risk score resulted in a decrease in physical component summary score (PCS), up to 10.7 points (p = 0.048) and in mental component summary score (MCS) (p = 0.044). Presence of respiratory symptoms was also associated with significantly decreased PCS and MCS (p < 0.001). Poor HRQoL was linked to higher perceived risk score with p ≤ 0.01 for all SF-36 dimensions. Asbestos exposure assessed by an expert was not associated with any outcome., Conclusions: All dimensions of HRQoL appear to be affected by the perceived risk of incurring asbestos-related disease and respiratory symptoms., (© 2024 The Author(s). American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Background: Previous studies have inconsistently reported associations between refractory ceramic fibers (RCFs) or mineral wool fibers (MWFs) and the presence of pleural plaques. All these studies were based on chest radiographs, known to be associated with a poor sensitivity for the diagnosis of pleural plaques., Research Question: Does the risk of pleural plaques increase with cumulative exposure to RCFs, MWFs, and silica? If the risk does increase, do these dose-response relationships depend on the co-exposure to asbestos or, conversely, are the dose-response relationships for asbestos modified by co-exposure to RCFs, MWFs, and silica?, Study Design and Methods: Volunteer workers were invited to participate in a CT scan screening program for asbestos-related diseases in France. Asbestos exposure was assessed by industrial hygienists, and exposure to RCFs, MWFs, and silica was determined by using job-exposure matrices. A cumulative exposure index (CEI) was then calculated for each subject and separately for each of the four mineral particle exposures. All available CT scans were submitted to randomized double reading by a panel of radiologists., Results: In this cohort of 5,457 subjects, significant dose-response relationships were determined after adjustment for asbestos exposure between CEI to RCF or MWF and the risk of PPs (ORs of 1.29 [95% CI, 1.00-1.67] and 1.84 [95% CI, 1.49-2.27] for the highest CEI quartile, respectively). Significant interactions were found between asbestos on one hand and MWF or RCF on the other., Interpretation: This study suggests the existence of a significant association between exposure to RCFs and MWFs and the presence of pleural plaques in a large population previously exposed to asbestos and screened by using CT scans., (Copyright © 2023. Published by Elsevier Inc.)

Context.—: Homozygous deletion (HD) of CDKN2A is one of the most frequent genetic abnormalities in pleural mesotheliomas. HD of CDKN2A by fluorescence in situ hybridization (FISH) is a reliable marker of malignancy in mesothelial proliferations; however, evaluation of CDKN2A deletion requires FISH. The 9p21 locus includes both CDKN2A and MTAP (methylthioadenosine phosphorylase); the latter is frequently codeleted with CDKN2A., Objective.—: To examine the question of whether immunohistochemistry for MTAP and p16, the protein product of CDKN2A, can serve as a surrogate for CDKN2A HD by FISH., Design.—: A random selection of 125 pleural mesothelioma cases was divided into 3 groups for evaluation of p16 and MTAP expression compared with FISH for CDKN2A deletion: 53 with HD, 39 with heterozygous deletion, and 33 without deletion., Results.—: By itself, loss of p16 nuclear expression (<1% staining) showed a high sensitivity (96%) but low specificity (43%) for CDKN2A HD by FISH. MTAP cytoplasmic expression loss (≤30% staining) showed a 97% specificity and 69% sensitivity. The combination of p16 nuclear (<1% staining) and MTAP cytoplasmic (≤30% staining) loss demonstrated both high specificity (96%) and high sensitivity (86%). Patients with retained p16 expression (≥1%) had the best prognosis, whereas a p16 (<1%)/MTAP loss combination was associated with a dismal prognosis., Conclusions.—: MTAP immunohistochemical staining is a valid surrogate marker for CDKN2A HD by FISH; however, to obtain the same accuracy as the FISH assay, a combination of nuclear p16 and cytoplasmic MTAP staining is recommended. These findings correlate with prognosis.

Objectives: The aim of this study was to analyse, within a French cohort of workers previously occupationally exposed to asbestos, incidence and mortality from various sites of head and neck cancers (larynx excluded) and to examine the potential link of these cancers with pleural plaques., Methods: A 10-year follow-up study was conducted in the 13 481 male subjects included in the cohort between October 2003 and December 2005. Asbestos exposure was assessed by industrial hygienist analysis of a standardised questionnaire. The final cumulative exposure index (CEI; in equivalent fibres.years/mL) for each subject was calculated as the sum of each employment period's four-level CEI. The number of head and neck cancers recorded by the National Health Insurance fund was collected in order to conduct an incidence study. Complementary analysis was restricted to men who had performed at least one chest CT scan (N=4804). A mortality study was also conducted. We used a Cox model with age as the time axis variable adjusted for smoking, time since first exposure, CEI of exposure to asbestos and pleural plaques on CT scans., Results: We reported a significant dose-response relationship between CEI of exposure to asbestos and head and neck cancers after exclusion of laryngeal cancers, in the mortality study (HR 1.03, 95% CI (1.01 to 1.06) for an increase of 10 f.years/mL) and a close to significant dose-response relationship in the incidence study (HR 1.02, 95% CI (1.00 to 1.04) for an increase of 10 f.years/mL). No statistically significant association between pleural plaques and head and neck cancer incidence was observed., Conclusions: This large-scale study suggests a relationship between asbestos exposure and head and neck cancers, after exclusion of laryngeal cancers, regardless of whether associated pleural plaques were present., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : The National Lung Screening Trial (NLST) and NELSON study opened the debate on the relevance of lung cancer (LC) screening in subjects exposed to occupational respiratory carcinogens. This analysis reported the incremental cost-effectiveness ratios (ICER) of an organized LC screening program for an asbestos-exposed population. Methods: Using Markov modelization, individuals with asbestos exposure were either monitored without intervention or annual low-dose thoracic computed-tomography (LDTCT) scan LC screening. LC incidence came from a prospective observational cohort of subjects with occupational asbestos exposure. The intervention parameters were those of the NLST study. Utilities and LC-management costs came from published reports. A sensitivity analysis evaluated different screening strategies. Results: The respective quality-adjusted life year (QALY) gain, supplementary costs and ICER [95% confidence interval] were: 0.040 [0.010-0.065] QALY, 6900 [3700-11,800] € and 170,000 [75,000-645,000] €/QALY for all asbestos-exposed subjects; and 0.144 [0.071-0.216] QALY, 13,000 [5700-26,800] € and 90,000 [35,000-276,000] €/QALY for smokers with high exposure. When screening was based on biennial LDTCT scans, the ICER was 45,000 [95% CI: 15,000-116,000] €/QALY. Conclusions: Compared to the usual ICER thresholds, biennial LDTCT scan LC screening for smokers with high occupational exposure to asbestos is acceptable and preferable to annual scans.

Background: Occupational asbestos exposure is associated with pleural plaques (PP), a benign disease often seen as a marker of past exposure to asbestos and lung cancer. The association between these two diseases has not been formally proved, the aim of this study was to evaluate this association in the asbestos-related disease cohort (ARDCO) cohort., Methods: ARDCO is a French multicentric cohort including workers formerly occupationally exposed to asbestos from 2003 to 2005. CT scan was performed to diagnose PP with double reading and lung cancer (incidence and mortality) was followed through health insurance data and death certificates. Cox models were used to estimate the association between PP and lung cancer adjusting for occupational asbestos exposure (represented by cumulative exposure index, time since first exposure and time since last exposure) and smoking status., Results: A total of 176 cases (of 5050 subjects) and 88 deaths (of 4938 subjects) of lung cancer were recorded. Smoking status was identified as an effect modifier. Lung cancer incidence and mortality were significantly associated with PP only in non-smokers, respectively, HR=3.13 (95% CI 1.04 to 9.35) and HR=16.83 (95% CI 1.87 to 151.24) after adjustment for age, occupational asbestos exposure and smoking status., Conclusions: ARDCO study was the first to study this association considering equal asbestos exposure, and more specifically, our study is the first to test smoking as an effect modifier, so comparison with scientific literature is difficult. Our results seem to consolidate the hypothesis that PP may be an independent risk factor for lung cancer but they must be interpreted with caution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Silicon dioxide (SiO2) is a mineral compound present in the Earth’s crust in two mineral forms: crystalline and amorphous. Based on epidemiological and/or biological evidence, the pulmonary effects of crystalline silica are considered well understood, with the development of silicosis, emphysema, chronic bronchitis, or chronic obstructive pulmonary disease. The structure and capacity to trigger oxidative stress are recognized as relevant determinants in crystalline silica’s toxicity. In contrast, natural amorphous silica was long considered nontoxic, and was often used as a negative control in experimental studies. However, as manufactured amorphous silica nanoparticles (or nanosilica or SiNP) are becoming widely used in industrial applications, these paradigms must now be reconsidered at the nanoscale (<100 nm). Indeed, recent experimental studies appear to point towards significant toxicity of manufactured amorphous silica nanoparticles similar to that of micrometric crystalline silica. In this article, we present an extensive review of the nontumoral pulmonary effects of silica based on in vitro and in vivo experimental studies. The findings of this review are presented both for micro- and nanoscale particles, but also based on the crystalline structure of the silica particles.

Background: Mineralogical analyses of bronchoalveolar lavage (BAL) may help in assessing past exposure to mineral particles. However, their interpretation relies on their quality, meaning their representativeness of the alveolar compartment. The aim of this study was to find predictive factors of BAL samples quality allowing a reliable mineralogical analysis., Methods: All BAL samples analyzed between 2018 and 2020 in the Asbestos Fibers and Particles Laboratory from Paris City were included. They were read by an experienced cyto-pathologist and validated according to their representativeness of the alveolar region compartment. Univariate and stratified analyses were conducted to identify factors associated with the samples' cytological quality., Results: On the 780 samples included, 64.4% were deemed of good cytological quality and 17.9% were not interpretable. Injected volume and BAL yield (recovery volume on injected volume ratio) were associated with cytological quality. Injecting at least 100mL with a ≥60% yield or injecting at least 150mL with a ≥30% yield allowed having a good proportion of BAL with sufficient cytological quality., Conclusions: Injected volume greater than 100mL with sufficient BAL yield are essential factors to ensure a reliable mineralogical analysis of BAL samples., Competing Interests: Declarations of interest None., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)

Objective: This study aimed to develop and validate an automated artificial intelligence (AI)-driven quantification of pleural plaques in a population of retired workers previously occupationally exposed to asbestos., Methods: CT scans of former workers previously occupationally exposed to asbestos who participated in the multicenter APEXS (Asbestos PostExposure Survey) study were collected retrospectively between 2010 and 2017 during the second and the third rounds of the survey. A hundred and forty-one participants with pleural plaques identified by expert radiologists at the 2nd and the 3rd CT screenings were included. Maximum Intensity Projection (MIP) with 5 mm thickness was used to reduce the number of CT slices for manual delineation. A Deep Learning AI algorithm using 2D-convolutional neural networks was trained with 8280 images from 138 CT scans of 69 participants for the semantic labeling of Pleural Plaques (PP). In all, 2160 CT images from 36 CT scans of 18 participants were used for AI testing versus ground-truth labels (GT). The clinical validity of the method was evaluated longitudinally in 54 participants with pleural plaques., Results: The concordance correlation coefficient (CCC) between AI-driven and GT was almost perfect (>0.98) for the volume extent of both PP and calcified PP. The 2D pixel similarity overlap of AI versus GT was good (DICE = 0.63) for PP, whether they were calcified or not, and very good (DICE = 0.82) for calcified PP. A longitudinal comparison of the volumetric extent of PP showed a significant increase in PP volumes ( p < 0.001) between the 2nd and the 3rd CT screenings with an average delay of 5 years., Conclusions: AI allows a fully automated volumetric quantification of pleural plaques showing volumetric progression of PP over a five-year period. The reproducible PP volume evaluation may enable further investigations for the comprehension of the unclear relationships between pleural plaques and both respiratory function and occurrence of thoracic malignancy.

We report nine examples of a previously undescribed type of peritoneal circumscribed nodular mesothelial tumor characterized by nests or sheets of mesothelial cells with sharp cell borders and extremely bland, sometimes grooved, nuclei. In some cases, nests were separated by fibrous bands. All patients were women, age range 30-72 years (median 52 years). All tumors were incidental findings during surgery and grossly were either solitary nodules or a few small nodules on the peritoneal surface. Referring pathologic diagnoses included diffuse malignant mesothelioma, localized malignant mesothelioma, well-differentiated papillary mesothelioma, and adenomatoid tumor. No tumor showed BAP1 loss by immunohistochemistry nor deletion of CDKN2A by FISH. RNA-seq revealed that these tumors clustered together and were distinct from peritoneal diffuse malignant mesotheliomas. Very few mutations or translocations were found, none of them recurrent from tumor to tumor, and no tumor showed an abnormality in any of the genes typically mutated/deleted in diffuse malignant mesothelioma. Array CGH on three cases revealed two with a completely flat profile and one with a small deletion at 3q26-3q28. On follow-up (range 5-60, median 34 months), there were no deaths, no recurrences, and no evidence of metastatic disease nor local spread; one case that initially had scattered nodules on the pelvic peritoneum had the same pattern of nodules at a second look operation 2 years later. We propose the name solid papillary mesothelial tumor for these lesions. These appear to be either benign or very low-grade tumors that need to be separated from malignant mesotheliomas., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Work-related asthma (WRA) accounts for 10-25% of all adult asthma. It therefore seems important to raise questions regarding an asthmatic's approach to occupational or job training activities. WRA takes on two forms: work-exacerbated asthma (WEA) and occupational asthma (OA), which encompasses different subtypes of heterogeneous mechanisms. It currently represents a major challenge for occupational medicine in terms of detailed diagnosis, social care, the economic repercussions for workers and employers and, last but not least, social insurance. This review aims to sensitize health care practitioners to the peculiarities of WRA management in routine practice. More specifically, prognosis depends on early diagnosis, medical care and work adjustment measures. WEA and OA are explained in detail in view of identifying causative agents and at-risk occupations and defining adapted medical strategy. Relevant lines of questioning and complementary exams are presented. In addition, the key role of the occupational physician, especially as regards recognition and identification of occupational disease, is underlined, the objective being to facilitate optimal professional and social management. In future studies, the key role of counseling and orientation mechanisms should be highlighted as means of preventing WRA occurrence., (Copyright © 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

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 <25%, moderate: between 25 and 50% and severe: >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.

Non-Hodgkin lymphoma (NHL), multiple myeloma and chronic lymphocytic leukemia are possibly related to environmental and/or occupational exposure. The primary objective of this study was to develop a questionnaire for screening patients with these blood disorders who might benefit from a specialized consultation for possible recognition of the disease as an occupational disease. The study included 205 subjects (male gender, 67.3%; mean age, 60 years; NHL, 78.5%). The questionnaire performed very satisfactorily in identifying the exposures most frequently retained by experts for their potential involvement in the occurrence of NHL. Its sensitivity and specificity in relation to the final expertise were 96% and 96% for trichloroethylene, 85% and 82% for benzene, 78% and 87% for solvents other than trichloroethylene and dichloromethane, 87% and 95% for pesticides, respectively. Overall, 15% of the subjects were invited to ask National Social Insurance for compensation as occupational disease. These declarations concerned exposure to pesticides (64%), solvents (trichloroethylene: 29%; benzene: 18%; other than chlorinated solvents: 18%) and sometimes multiple exposures. In conclusion, this questionnaire appears as a useful tool to identify NHL patients for a specialized consultation, in order to ask for compensation for occupational disease.

Objectives: Although healthcare workers (HCWs) have been particularly affected by SARS-CoV-2, detailed data remain scarce. In this study, we investigated infection rates, clinical characteristics, occupational exposure and household transmission among all symptomatic HCWs screened by SARS-CoV-2 RT-PCR between 17 March (French lockdown) and 20 April., Methods: SARS-CoV-2 RT-PCR was proposed to symptomatic (new cough or dyspnoea) HCWs at Creteil Hospital in one of the Parisian suburbs most severely affected by COVID-19. Data on occupational profile, living situation and household, together with self-isolation and mask use at home were collected, as well as the number of cases in the household., Results: The incidence rate of symptomatic SARS-CoV-2 was estimated to be 5% (110/2188). A total of 110 (35%) of the 314 HCWs tested positive and 9 (8%) were hospitalised. On multivariate analysis, factors independently associated with positive RT-PCR were occupational profile with direct patient facing (OR 3.1, 95% CI 1.1 to 8.8), p<0.03), and presence of anosmia (OR 5.7, 95% CI 3.1 to 10.6), p<0.0001). Being a current smoker was associated with negative RT-PCR (OR 0.3, 95% CI 0.1 to 0.7), p=0.005). Transmission from HCWs to household members was reported in 9 (14%) cases, and 2 deaths occurred. Overall, self-isolation was possible in 52% of cases, but only 31% of HCWs were able to wear a mask at home., Conclusion: This is the first study to report infection rates among HCWs during the peak of the SARS-CoV-2 epidemic in France and the lockdown period, highlighting the risk related to occupational profile and household transmission., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres., (© The article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery and the European Respiratory Journal. All rights reserved in respect of European Journal of Cardio-Thoracic Surgery, © European Association for Cardio-Thoracic Surgery 2020 and European Respiratory Journal, © European Respiratory Society 2020. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A ( p16 ) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres., Competing Interests: Conflict of interest: A. Scherpereel reports personal fees for advisory board work from AstraZeneca, BMS, MSD, Roche and Janssen, non-financial support for meeting attendance from BMS, MSD and Roche, institutional support for clinical trial participation from Astra-Zeneca/MedImmune, BMS, Verastem and Bayer, grants from BMS, outside the submitted work. Conflict of interest: I. Opitz has nothing to disclose. Conflict of interest: T. Berghmans has nothing to disclose. Conflict of interest: I. Psallidas works as a Medical Science Director for AstraZeneca, outside the submitted work; membership of the task force was resigned when this position became effective. Conflict of interest: M. Glatzer has nothing to disclose. Conflict of interest: D. Rigau works as methodologist for the European Respiratory Society. Conflict of interest: P. Astoul has nothing to disclose. Conflict of interest: S. Bölükbas has nothing to disclose. Conflict of interest: J. Boyd is an employee of the European Respiratory Society. Conflict of interest: J. Coolen has nothing to disclose. Conflict of interest: C. De Bondt has nothing to disclose. Conflict of interest: D. De Ruysscher reports grants from Bristol-Myers-Squibb AstraZeneca, Celgene, Roche/Genentech and Merck/ Pfizer, outside the submitted work. Conflict of interest: V. Durieux has nothing to disclose. Conflict of interest: C. Faivre-Finn has nothing to disclose. Conflict of interest: D. Fennell reports personal fees and non-financial support from BMS and MSD, non-financial support from Eli Lilly, Clovis, Bergen Bio and Pierre Fabre, grants, personal fees and non-financial support from Roche-Genentech, personal fees from Aldeyra, during the conduct of the study. Conflict of interest: F. Galateau-Salle has nothing to disclose. Conflict of interest: L. Greillier reports grants, personal fees and non-financial support from Roche and Novartis, personal fees and non-financial support from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, Abbvie and MSD, outside the submitted work. Conflict of interest: M.A. Hoda has nothing to disclose. Conflict of interest: W. Klepetko has nothing to disclose. Conflict of interest: A. Lacourt has nothing to disclose. Conflict of interest: P. McElnay was employed by GlaxoSmithKline, outside the submitted work. Conflict of interest: N.A. Maskell has nothing to disclose. Conflict of interest: L. Mutti has nothing to disclose. Conflict of interest: J-C. Pairon reports grants from Santé Publique France Agency and French National Health Insurance (CNAM-TS), outside the submitted work. Conflict of interest: P. Van Schil has nothing to disclose. Conflict of interest: J.P. van Meerbeeck has nothing to disclose. Conflict of interest: D. Waller has nothing to disclose. Conflict of interest: W. Weder reports personal fees from AstraZeneca for advisory board work and lectures, grants and personal fees for lectures from Covidien. Conflict of interest: G. Cardillo has nothing to disclose. Conflict of interest: P.M. Putora reports grants from AstraZeneca and Celgene, outside the submitted work., (The article has been co-published with permission in the European Respiratory Journal and the European Journal of Cardio-Thoracic Surgery. All rights reserved in respect of European Respiratory Journal, © European Respiratory Society 2020 and European Journal of Cardio-Thoracic Surgery, © European Association for Cardio-Thoracic Surgery 2020. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Introduction: Histologic subtypes of malignant pleural mesothelioma are a major prognostic indicator and decision denominator for all therapeutic strategies. In an ambiguous case, a rare transitional mesothelioma (TM) pattern may be diagnosed by pathologists either as epithelioid mesothelioma (EM), biphasic mesothelioma (BM), or sarcomatoid mesothelioma (SM). This study aimed to better characterize the TM subtype from a histological, immunohistochemical, and molecular standpoint. Deep learning of pathologic slides was applied to this cohort., Methods: A random selection of 49 representative digitalized sections from surgical biopsies of TM was reviewed by 16 panelists. We evaluated BAP1 expression and CDKN2A (p16) homozygous deletion. We conducted a comprehensive, integrated, transcriptomic analysis. An unsupervised deep learning algorithm was trained to classify tumors., Results: The 16 panelists recorded 784 diagnoses on the 49 cases. Even though a Kappa value of 0.42 is moderate, the presence of a TM component was diagnosed in 51%. In 49% of the histological evaluation, the reviewers classified the lesion as EM in 53%, SM in 33%, or BM in 14%. Median survival was 6.7 months. Loss of BAP1 observed in 44% was less frequent in TM than in EM and BM. p16 homozygous deletion was higher in TM (73%), followed by BM (63%) and SM (46%). RNA sequencing unsupervised clustering analysis revealed that TM grouped together and were closer to SM than to EM. Deep learning analysis achieved 94% accuracy for TM identification., Conclusion: These results revealed that the TM pattern should be classified as non-EM or at minimum as a subgroup of the SM type., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: In France, long-term follow-up after occupational exposure to asbestos is recommended. This study looked at the psychological consequences in the longer term following a CT-scan, in particular the impact of having received compensation for an occupational disease., Methods: As part of an asbestos post-exposure survey study (APExS), volunteers from Normandy were asked to complete self-assessment questionnaires about their psychological condition at different points during follow-up, including a psychological questionnaire before, then 6 months, and finally 18 to 24 months after their chest CT-scan. Information collected from 622 individuals were analyzed based on information provided as to the result of the screening and whether they had received compensation for having an occupational disease., Results: The identification of an occupational disease eligible for compensation is associated with a long term increase in psychological distress. The impact of psychological state during follow-up is greater in men who reported receiving occupational disease compensation. The discovery of an asbestos-related disease during the screening is associated with a negative perception of general health and an increase in psychological distress., Conclusion: The receipt of compensation of an occupational disease does not seem to compensate for the negative psychological impact related to the discovery of a disease during the asbestos post-exposure follow-up., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options., Methods: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples., Findings: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series., Interpretation: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response., (Copyright © 2018. Published by Elsevier B.V.)

Rationale: As pleural plaque has been reported as a risk factor in the occurrence of lung cancer and mesothelioma, a reproducible and precise method of measurement of pleural plaque volume (PPV) is needed to further describe these relationships. The aim of the study was to assess the reproducibility of a 3-dimensional computed tomography (3D-CT) volumetric analysis of PPV in patients with occupational exposure to asbestos., Material and Methods: A total of 28 patients were retrospectively randomly selected from the multicenter APEXS (Asbestos Post Exposure Survey) study, which was held between 2003 and 2005. All patients underwent a 3D-CT scan. Two readers specialized in chest radiology completed the 3D semiautomated quantification of lung volume using dedicated software. They also had to categorize the visual extent of pleural plaque in terms of thickness and circumference. Reproducibility of the continuous PPV variable was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Reproducibility of categorical variables was assessed using the κ test., Results: Intraobserver reproducibility of PPV was almost perfect (ICC=0.98 [95% interval: 0.97-0.99]), and interobserver reproducibility was very good (ICC=0.93 [0.88-0.97]). At Bland-Altman analysis, the mean differences were 0.1 (limit of agreement: -11.0 to 11.2) and 3.7 cc (-17.8 to 25.2), respectively. Visual analysis of both plaque in terms of thickness and circumference were fair to moderate, with κ values ranging from 0.30 to 0.60., Conclusions: 3D semiautomatic quantification of PPV is feasible and reproducible using CT in patients with occupational exposure to asbestos. PPV measurement may be useful to correlate with other asbestos-related disease outcomes and prognosis.

Introduction: Guidelines concerning the follow-up of subjects occupationally exposed to lung carcinogens, published in France in 2015, recommended the setting up of a trial of low-dose chest CT lung cancer screening in subjects at high risk of lung cancer., Objective: To evaluate the organisation of low-dose chest CT lung cancer screening in subjects occupationally exposed to lung carcinogens and at high risk of lung cancer., Methods and Analysis: This trial will be conducted in eight French departments by six specialised reference centres (SRCs) in occupational health. In view of the exploratory nature of this trial, it is proposed to test initially the feasibility and acceptability over the first 2 years in only two SRCs then in four other SRCs to evaluate the organisation. The target population is current or former smokers with more than 30 pack-years (who have quit smoking for less than 15 years), currently or previously exposed to International Agency for Research on Cancer group 1 lung carcinogens, and between the ages of 55 and 74 years. The trial will be conducted in the following steps: (1) identification of subjects by a screening invitation letter; (2) evaluation of occupational exposure to lung carcinogens; (3) evaluation of the lung cancer risk level and verification of eligibility; (4) screening procedure: annual chest CT scans performed by specialised centres and (5) follow-up of CT scan abnormalities., Ethics and Dissemination: This protocol study has been approved by the French Committee for the Protection of Persons. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings., Trial Registration Number: NCT03562052; Pre-results., Competing Interests: Competing interests: OB declares competing interest with MSD and Astra-Zeneca. VLD declares competing interest with GSK and Pierre Fabre. Other authors declare that they have no competing interest., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Compensation for occupational pulmonary diseases requires the establishment of guidelines based on standardized and objective criteria, in order to provide compensation that is as fair as possible to patients who suffer from them. A review of the elements necessary for the examination of an individual file was carried out by a working group. It is accepted that respiratory functional exploration is the key element in assessing the level of permanent disability in all of these conditions, with the exception of thoracic malignancies. Guiding scales have been developed for the respiratory impairment of three types of conditions: occupational asthma, thoracic malignancy, and other respiratory diseases. Additional criteria for increasing the permanent disability level are also proposed in order to take into account professional prejudice, in particular the possibility or not of continuing the occupational activity, in the same job or after changing to another. For certain respiratory diseases, a periodic reassessment of the initially attributed permanent disability level is recommended as well as the initial one at the time of definitive cessation of occupational activity., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components., Methods: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis., Results: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02)., Conclusions: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator., (Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.)

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1- and 2-year survival according to sex, age, co-morbidities, management, population-density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co-morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One- and 2-year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7-15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co-morbidities, living in rural/semi-rural area was associated with better 2-year survival (HR: 0.83 [95% CI: 0.73-0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co-morbidities, sex, age, and living place appear to be significant factors of prognosis., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Nanoparticles (NPs) can be toxic, depending on their physico-chemical characteristics. Macroautophagy/autophagy could represent a potential underlying mechanism of this toxicity. We therefore set up a study aimed to characterize in depth the effects, on autophagy, of macrophage exposure to NPs, with a particular attention paid to the role of NP physico-chemical characteristics (specifically chemical composition, shape, size, length, crystal phase, and/or surface properties). We demonstrate that exposure to carbon nanotubes (CNT) but not to spherical NPs leads to the blockage of the autophagic flux. We further identified lysosomal dysfunction, in association with the downregulation of SNAPIN expression, as the underlying mechanism responsible for the CNT-induced autophagy blockade. These results identify for the first time the shape as a major determinant of the interaction of NPs with the autophagy pathway. Moreover, identifying the lysosomes and SNAPIN as primary targets of MWCNT toxicity opens new directions in the interpretation and understanding of nanomaterial toxicity.

Background: The objective of the study was to compare the prevalence of occupational exposure to asbestos and crystalline silica according to histological types of lung cancer and age at diagnosis., Methods: CaProMat study is a pooled case-only study conducted between 1996 and 2011. The current study consisted of 6521 lung cancer cases. Occupational exposure to asbestos and crystalline silica was assessed by two Job-Exposure Matrices. A weighted prevalence of exposure was derived and compared according to histological types and age at diagnosis., Results: There was no difference of weighted prevalence of exposure to asbestos and crystalline silica according to histological types of lung cancer. There was a statistically significant difference of weighted prevalence of exposure to asbestos and crystalline silica according to age at diagnosis., Conclusions: Due to the limited clinical importance of the difference, neither the histological type, nor the age at diagnosis can be used as an indicator for the occupational exposure to asbestos or crystalline silica., (© 2017 Wiley Periodicals, Inc.)

Background: Our study aimed at analyzing incidence and mortality from esophageal cancer within a cohort of workers with previous occupational asbestos exposure (ARDCo Program)., Methods: A 10-year follow-up study was conducted in the 14 515 male subjects included in this program between October 2003 and December 2005. Follow-up began when exposure stopped. Asbestos exposure was analyzed by industrial hygienists using data from a standardized questionnaire. The Cox model was used, with age as the time axis variable adjusted for smoking, time since first exposure (TSFE) and cumulative exposure index (CEI) of exposure to asbestos., Results: We reported a significant dose-response relationship between CEI of exposure to asbestos and esophageal cancer, in both incidence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.58), and mortality (HR 1.40, [95%CI 1.12-1.75])., Conclusions: This large-scale study suggests the existence of a relationship between asbestos exposure and cancer of the esophagus., (© 2017 Wiley Periodicals, Inc.)

Objectives: The aim of this study was to assess the effect modification of the association between tobacco smoking and phenotypes of lung cancer (histological type, tumor location, and age at diagnosis) by occupational exposure to asbestos or to crystalline silica., Materials and Methods: The CaProMat study is a pooled case-only study including 7256 male lung cancer cases recruited between 1996 and 2011 in France and Canada. Two job-exposure matrices (JEMs) were used to assess occupational exposure to asbestos and crystalline silica. Statistical interactions between tobacco smoking and occupational exposure to asbestos or crystalline silica were assessed using unconditional logistic regression models for histological type and tumor location and linear regression models for age at diagnosis., Results: Tobacco smoking was associated with squamous cell carcinoma and small cell carcinomas as well as an earlier age at diagnosis. Additional exposure to either asbestos or crystalline silica did not modify the effect of tobacco smoking for either histological type or age at diagnosis. Neither tobacco smoking nor occupational exposure to asbestos or crystalline silica influenced tumor location., Conclusions: Tobacco smoking was the main factor related to histological type and age at diagnosis. Those associations were not modified by occupational exposure to asbestos or crystalline silica., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Due to the growing commercial applications of manufactured nanoparticles (NPs), toxicological studies on NPs, especially during the critical window of development, are of major importance. The aim of the study was to assess the impact of respiratory exposure to metallic and metal oxide NPs during pregnancy on lung development of the offspring and to determine the key parameters involved in lung alterations. Pregnant mice were exposed to weekly doses of 100 μg (total dose 300 μg) of titanium dioxide (TiO 2 ), cerium oxide (CeO 2 ), silver (Ag) NPs or saline solution by nonsurgical intratracheal instillation. The offspring lungs were analyzed at different stages of lung development: fetal stage (gestational day 17.5), pulmonary alveolarization (post-delivery day 14.5) and lung maturity (post-delivery day 49.5). Regardless of the type of NP, maternal exposure during gestation induced long-lasting impairment of lung development of the offspring. This effect was accompanied by: i) decreased placental efficiency together with the presence of NPs in placenta, ii) no increase of inflammatory mediators present in amniotic fluid, placenta or offspring lungs and iii) decreased pulmonary expression of vascular endothelial growth factor-α (VEGF-α) and matrix metalloproteinase 9 (MMP-9) at the fetal stage, and fibroblast growth factor-18 (FGF-18) at the alveolarization stage. Respiratory exposure to metallic NPs during pregnancy induces stereotyped impairment of lung development with a lasting effect in adult mice, independently of the chemical nature of the NP.

Background: Asbestos is known to be an independent risk factor for lung and pleural cancers. However, to date, little attention has been paid to the psychological effects of asbestos exposure among exposed subjects. The objectives of this study were to estimate the prevalence of anxious and depressive symptoms among >2000 French participants of the Asbestos-Related Diseases Cohort (ARDCO), 6 years after their inclusion, to identify the risk factors associated with those anxious and depressive symptoms and to evaluate the impact of the asbestos-risk perception., Methods: The ARDCO was constituted in four regions of France between October 2003 and December 2005, by including former asbestos workers. Between 2011 and 2012, participants of the ARDCO program were invited to undergo another chest CT scan 6 years after the previous scan. Participants were asked to complete questionnaires including asbestos exposure assessment, Hospital Anxiety and Depression Scale (HADS), asbestos-risk perception and self-perception of asbestos-related diseases., Results: Among the 2225 participants, 2210 fully completed questionnaires were collected and analyzed. The prevalence of symptoms of probable anxiety and probable depression was 19.7% and 9.9%, respectively. The risk of anxious and depressive symptoms was independently associated with self-perception of the intensity of asbestos exposure, asbestos-risk perception and self-perception of asbestos-related diseases., Conclusion: The results obtained in this large study confirm that previously asbestos-exposed subjects are likely to develop anxious and depressive symptoms. Finally, implications related to the prevention of anxiety and depression among asbestos-exposed workers is discussed., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: The relationships between asbestos exposure and colorectal cancer remain controversial., Objectives: We examined the association between asbestos exposure and colorectal cancer incidence., Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample., Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20-40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0-20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20-40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases., Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming's S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409-415; http://dx.doi.org/10.1289/EHP153.

In spite of the great promises that the development of nanotechnologies can offer, concerns regarding potential adverse health effects of occupational exposure to nanoparticle (NP) is raised. We recently identified metal oxide NP in lung tissue sections of welders, located inside macrophages infiltrated in fibrous regions. This suggests a role of these NP in the lung alterations observed in welders. We therefore designed a study aimed to investigate the pulmonary effects, in mice, of repeated exposure to NP administered at occupationally relevant doses. We therefore chose four metal oxide NPs representative of those found in the welder's lungs: Fe 2 O 3 , Fe 3 O 4 , MnFe 2 O 4 and CrOOH. These NPs were administered weekly for up to 3 months at two different doses: 5 μg, chosen as occupationally relevant to welding activity, and 50 μg, chosen as occupationally relevant to the context of an NP-manufacturing facility. Our results show that 3 month-repeated exposures to 5 μg NP induced limited pulmonary effects, characterized by the development of a mild peribronchiolar fibrosis observed for MnFe 2 O 4 and CrOOH NP only. This fibrotic event was further extended in terms of intensity and localization after the repeated administration of 50 μg NP: all but Fe 2 O 3 NP induced the development of peribronchiolar, perivascular and alveolar fibrosis, together with an interstitial inflammation. Our data demonstrate for the first time a potential risk for respiratory health posed by repeated exposure to NP at occupationally relevant doses. Given these results, the development of occupational exposure limits (OELs) specifically dedicated to NP exposure might therefore be an important issue to address.

Objective: We aimed to review the literature regarding the dose-response relationship between occupational exposure to chemicals classified by the International Agency for Research on Cancer (IARC) as carcinogenic agents and the risk of some lung cancers and on any combined effect with tobacco exposure on lung cancer risk., Methods: A literature search was performed in three databases as well as in the IARC monographs between January 1990 and April 2015., Results: The literature is abundant for some carcinogens such as asbestos, crystalline silica and diesel exhaust fumes but is more sparse for many carcinogens and particularly any interaction with tobacco on lung cancer risk., Conclusion: Few data exist for most lung occupational carcinogens including their interaction with tobacco exposure. In the case of exposure to occupational carcinogens and co-exposure to tobacco smoke, there is a dual primary prevention objective: the elimination of both occupational risk factors and tobacco smoke., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Despite the reduction of global asbestos consumption and production due to the ban or restriction of asbestos uses in more than 50 countries since the 1970s, malignant mesothelioma remains a disease of concern. Asbestos is still used, imported, and exported in several countries, and the number of mesothelioma deaths may be expected to increase in the next decades in these countries. Asbestos exposure is the main risk factor for malignant pleural mesothelioma, but other types of exposures are linked to the occurrence of this type of cancer. Although recent treatments improve the quality of life of patients with mesothelioma, malignant pleural mesothelioma remains an aggressive disease. Recent treatments have not resulted in appreciable improvement in survival, and thus development of more efficient therapies is urgently needed. The development of novel therapeutic strategies is dependent on our level of knowledge of the physiopathological and molecular changes that mesothelial cells acquired during the neoplastic process. During the past 5 years, new findings have been published on the etiology, epidemiology, molecular changes, and innovative treatments of malignant pleural mesothelioma. This review aims to update the findings of recent investigations on etiology, epidemiology, and molecular changes with a focus on (1) attributable risk of asbestos exposure in men and women and (2) coexposure to other minerals and other elongated mineral particles or high aspect ratio nanoparticles. Recent data obtained on genomic and gene alterations, pathways deregulations, and predisposing factors are summarized.

Manufactured nanomaterials (MNMs) have the potential to improve everyday life as they can be utilised in numerous medical applications and day-to-day consumer products. However, this increased use has led to concerns about the potential environmental and human health impacts. The protein p53 is a key transcription factor implicated in cellular defence and reparative responses to various stress factors. Additionally, p53 has been implicated in cellular responses following exposure to some MNMs. Here, the role of the MNM mediated p53 induction and activation and its downstream effects following exposure to five well-characterised materials [namely two types of TiO2, two carbon black (CB), and one single-walled carbon nanotube (SWCNT)] were investigated. MNM internalisation, cellular viability, p53 protein induction and activation, oxidative stress, inflammation and apoptosis were measured in murine cell line and primary pulmonary macrophage models. It was observed that p53 was implicated in the biological responses to MNMs, with oxidative stress associated with p53 activation (only following exposure to the SWCNT). We demonstrate that p53 acted as an antioxidant and anti-inflammatory in macrophage responses to SWCNT and CB NMs. However, p53 was neither involved in MNM-induced cellular toxicity, nor in the apoptosis induced by these MNMs. Moreover, the physicochemical characteristics of MNMs seemed to influence their biological effects-SWCNT the materials with the largest surface area and a fibrous shape were the most cytotoxic in this study and were capable of the induction and activation of p53.

Given the results of experimental studies, occupational or environmental exposures to manufactured nanoparticles or to unintentionally produced ultrafine particles may result in health effects or diseases in humans. In this review, we synthesize published data of experimental studies on the distribution of inhaled nanoparticles and the first case reports to discuss the potential usefulness of their biological monitoring for clinical purposes. Toxicokinetic studies suggest that nanoparticles may be absorbed predominantly by respiratory and oral routes with possible systemic translocation, leading to accumulation in the peripheral organs or excretion in feces or urine. Some methods used in these studies may be applied successfully in retrospective evaluation of exposure or in follow-up of occupational exposure in the workplace. Biological monitoring of nanoparticles should be based on imaging methods that are essential to confirm their presence and to characterize them in tissue associated with analytical quantitative methods. The first case reports reviewed emphasize the urgent need for the development of standardized procedures for the preparation and analysis of biological samples with a view to characterizing and quantifying nanoparticles., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Rationale: Although asbestos is a well-known lung carcinogen, the pleural plaque-lung cancer link remains controversial., Objectives: This study was designed to examine this link in asbestos-exposed workers., Methods: A 6-year follow-up was conducted to study lung cancer mortality in the 5,402 male subjects participating in an asbestos-related disease screening program conducted from October 2003 to December 2005 in four French regions. Chest computed tomography (CT) scan was performed in all subjects with randomized, independent, double reading of CT scans focusing on benign asbestos-related abnormalities. Cox model survival regression analysis was used to model lung cancer mortality according to the presence of pleural plaques, with age as the main time variable, adjusting for smoking and asbestos cumulative exposure index. All statistical tests were two-sided., Measurements and Main Results: Thirty-six deaths from lung cancer were recorded. Lung cancer mortality was significantly associated with pleural plaques in the follow-up study in terms of both the unadjusted hazard ratio of 2.91 (95% confidence interval = 1.49-5.70) and the adjusted hazard ratio of 2.41 (95% confidence interval = 1.21-4.85) after adjustment for smoking and asbestos cumulative exposure index., Conclusions: Pleural plaques may be an independent risk factor for lung cancer death in asbestos-exposed workers and could be used as an additional criterion in the definition of high-risk populations eligible for CT screening.

Objectives: To investigate inter-reader agreement for the detection of pleural and parenchymal abnormalities using CT in a large cross-sectional study comprising information on individual cumulative exposure to asbestos., Methods: The project was approved by the hospital ethics committee, and all patients received information on the study and gave their written informed consent. In 5511 CT scans performed in a cohort of retired workers previously exposed to asbestos and volunteering to participate in a multiregional survey programme (Asbestos Related Diseases Cohort, ARDCO), double randomised standardised readings, triple in case of disagreement, were performed by seven trained expert radiologists specialised in thoracic imaging and blind to the initial interpretation. Inter-reader agreement was evaluated by calculating the κ-weighted coefficient between pairs of expert readers and results of routine practice and final diagnosis after expert reading., Results: κ-Weighted coefficients between trained experts ranged from 0.28 to 0.52 (fair to good), 0.59 to 0.86 (good to excellent) and 0.11 to 0.66 (poor to good) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively. κ-Weighted coefficients between results of routine practice and final diagnosis after expert reading were 0.13 (poor), 0.53 (moderate) and 0.11 (poor) for the diagnosis of asbestosis, pleural plaques and fibrosis of the visceral pleura, respectively., Conclusions: Interpretation of benign asbestos-related thoracic abnormalities requires standardisation of the reading and trained readers, particularly for participants asking for compensation, and with a view to the longitudinal survey of asbestos-exposed workers., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Occupational allergic contact dermatitis (OACD) is one of the most common occupational skin diseases in developed countries, but data about its temporal trends in incidence remain sparse., Objectives: The aim of this study is to describe OACD trends in terms of industrial activities and main causal agents in France over the period 2001-2010., Materials and Methods: Data were collected from the French National Network of Occupational Disease Vigilance and Prevention (RNV3P, Réseau National de Vigilance et de Prévention des Pathologies Professionnelles). All OACD considered probably or certainly associated with an occupational exposure were included in the study. Trends were examined (i) on annual crude numbers of OACD and (ii) on reported odds ratios of OACD calculated using logistic regression models., Results: Overall, 3738 cases of OACD were reported and the mean age of OACD cases was 35 years, 52% being women. The most frequent occupations were hairdressers, health care workers, cleaning staff and masons. The total number of OACD cases remained stable over the study period, but increases in OACD related to isothiazolinones (P = 0·002), epoxy resins (P = 0·012) and fragrances (P = 0·005) were observed. Conversely, decreases were noted for cement compounds (P = 0·002) and plant products (P = 0·031). These trends highlight specific sectors and exposures at risk of OACD., Conclusions: Trends in OACD depend on the nature of exposure. Observed decreases were consistent with prevention measures taken during the study period, and the increases observed serve to highlight those areas where preventative efforts need to be made to reduce skin allergies in the workplace., (© 2014 British Association of Dermatologists.)