Indoor exposure to ultrafine particles related to domestic activities: A systematic review and meta-analysis.

Ultrafine particles (< 100 nm) are of increasing concern because of their toxicological potential. Emission processes suggest their presence in all environments, including at home, where particularly at-risk populations may be exposed. However, knowledge of their impact on health is still limited, due to difficulties in properly assessing exposure in epidemiological studies. In this context, the objective of this study was to provide a complete summary of indoor exposure to ultrafine particles in highly industrialised countries by examining the domestic activities that influence such exposure. We conducted a systematic review, according to PRISMA guidelines using PubMed, Web of Science and Scopus up to and including 2021. We carried out a qualitative and quantitative analysis of the selected studies with a standardised template. Exposure circumstances, measurement methods, and results were analysed. Finally, a meta-analysis of the measured concentrations was performed to study exposure levels during domestic activities. The review included 69 studies resulting in the analysis of 346 exposure situations. Nine main groups of activities were identified: cooking, which was the most studied, smoking, the use of air-fresheners, cleaning, heating, personal care, printing, do-it-yourself activities, and others. Over 50 different processes were involved in these activities. Based on available particle number concentrations, the highest average of mean concentrations was associated with grilling (14,400 × 103 cm-3), and the lowest with wood stove (18 × 103 cm-3). The highest average of peak concentrations was that for the use of hair dryers (695 × 103 cm-3), and the lowest for the use of air cleaners (11 × 103 cm-3). A hierarchy of domestic activities and related processes leading to ultrafine particle exposure is provided, along with average exposure concentrations at home. However, more extensive measurement campaigns are needed under real-life conditions to improve assessments of indoor exposure to ultrafine particles.

Strategies to Assess Occupational Exposure to Airborne Nanoparticles: Systematic Review and Recommendations.

In many industrial sectors, workers are exposed to manufactured or unintentionally emitted airborne nanoparticles (NPs). To develop prevention and enhance knowledge surrounding exposure, it has become crucial to achieve a consensus on how to assess exposure to airborne NPs by inhalation in the workplace. Here, we review the literature presenting recommendations on assessing occupational exposure to NPs. The 23 distinct strategies retained were analyzed in terms of the following points: target NPs, objectives, steps, "measurement strategy" (instruments, physicochemical analysis, and data processing), "contextual information" presented, and "work activity" analysis. The robustness (consistency of information) and practical aspects (detailed methodology) of each strategy were estimated. The objectives and methodological steps varied, as did the measurement techniques. Strategies were essentially based on NPs measurement, but improvements could be made to better account for "contextual information" and "work activity". Based on this review, recommendations for an operational strategy were formulated, integrating the work activity with the measurement to provide a more complete assessment of situations leading to airborne NP exposure. These recommendations can be used with the objective of producing homogeneous exposure data for epidemiological purposes and to help improve prevention strategies.

Pleural Plaques and the Role of Exposure to Mineral Particles in the Asbestos Post-exposure Survey.

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.

Pleural plaques and risk of lung cancer in workers formerly occupationally exposed to asbestos: extension of follow-up.

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.

Head and neck cancer and asbestos exposure.

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.

Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).

BACKGROUND: Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. METHODS: Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. RESULTS: Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). CONCLUSIONS: NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.

Deep Learning for the Automatic Quantification of Pleural Plaques in Asbestos-Exposed Subjects.

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.

Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age.

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.

Development of a Job-Exposure Matrix for Ultrafine Particle Exposure: The MatPUF JEM.

OBJECTIVE: Ultrafine particles (UFPs) are generated from common work processes and have thus existed for a long time. Far more prevalent than engineered nanoparticles, they share common toxicological characteristics with them. However, there is no existing retrospective assessment tool specific to UFPs, for example, for epidemiological purposes. Thus, we aimed to develop a job-exposure matrix dedicated to UFPs. METHOD: Fifty-seven work processes were identified as well as the chemical composition of UFPs emitted, following a literature review and the input of an expert panel. These work processes were associated with occupational codes as defined by the ISCO 1968 classification. The probability and frequency of UFP exposure were assessed for each combination of occupational code and process. Summarized probabilities and frequencies were then calculated for all ISCO occupational codes associated with several processes. Variations in exposure over time or across industrial sectors were accounted for in the assessment of each occupational code. RESULTS: In the ISCO classification, 52.8% of the occupational codes (n = 835) assessed were associated with exposure to UFPs, consisting mainly of carbonaceous, metallic, and mineral families (39.5%, 22 and, 15.8%, respectively). Among them, 42.6% involved very probable exposure, and at a high frequency (regularly or continuously). CONCLUSION: These results suggest that occupational exposure to UFPs may be extensive at the workplace and could concern a wide variety of workers. Pending the integration of a third parameter assessing the intensity of UFP exposure, the MatPUF JEM already constitutes a promising and easy-to-use tool to study the possible adverse health effects of UFPs at work. It may also guide prevention policies in the occupational environments concerned, including those involving engineered nanoparticles.

A new trajectory approach for investigating the association between an environmental or occupational exposure over lifetime and the risk of chronic disease: Application to smoking, asbestos, and lung cancer.

Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.

Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system - Results from three French case-control studies.

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 2029 lung cancer cases and 2591 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.

What does ergonomics have to do with nanotechnologies? A case study.

Despite recent concerns for workers' health, exposure situations to nanoparticles can occur in numerous workplaces. Understanding how exposures occur considering human work in these transformations remains a crucial issue of nanotechnologies. The objective of this article is to understand exposure situations to nanoparticles, their determinants and the resources to act on them. This understanding was achieved by specific measurement of nanoparticles aerosols, combined with an analysis of work activity (actions performed and physical strain) in a rubber industry. The presentation of real time measurements, associated with the video of work situations, during confrontation interviews becomes a means of making exposing work activities visible, to analyze and transform them from the points of view formulated by the company's stakeholders. In this way, characterized "typical exposure situations" serve to trigger discussions and open up new spaces for debate highlighting how innovation affects work and gives rise to enhanced prevention projects.

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

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.

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

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.

Maternal occupational exposure to carbonaceous nanoscale particles and small for gestational age and the evolution of head circumference in the French Longitudinal Study of Children - Elfe study.

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.

Incidence and time trends of sarcoma (2000-2013): results from the French network of cancer registries (FRANCIM).

BACKGROUND: The exhaustive collection of new sarcoma cases and their second histologic review offer a unique opportunity to study their incidence and time trends in France according to the major subtypes. METHODS: Data were collected from population-based cancer registries covering 22% of the French population. Crude and world age-standardized incidence rates (ASR) were estimated according to anatomic, histological and genetic groups, age and sex over the 2010-2013 period. RESULTS: Time trends in incidence were calculated by the annual percent change over the 2000-2013 period. During the most recent period (2010-2013), 3942 patients with sarcoma were included. The ASR of soft-tissue and bone sarcomas, and gastro-intestinal stromal tumors (GIST) were 2.1, 1.0 and 0.6, respectively. For the four most frequent histological subtypes (unclassified, leiomyosarcoma, GIST and liposarcoma), the ASR ranged from 0.4 to 0.7. ASRs were 1.9 for complex genomic and 1.3 for recurrent translocation sarcomas. The time-trend analysis showed a significant increase of sarcoma incidence rate between 2000 and 2005, which stabilized thereafter. Incidence rates increased for four histological subtypes (GIST, chondrosarcoma, myxofibrosarcoma, solitary fibrous tumors) and decreased for three (leiomyosarcomas, Kaposi sarcoma and fibrosarcoma). CONCLUSION: To our knowledge, this study is the first to investigate sarcoma incidence based on a systematic pathological review of these cancers and on the updated sarcoma classifications. Due to the paucity of literature on sarcomas, future studies using data from population-based cancer registries should consider a standardized inclusion criterion presented in our study to better describe and compare data between countries.

ETIOSARC study : environmental aetiology of sarcomas from a French prospective multicentric population-based case-control study-study protocol.

INTRODUCTION: Sarcomas are rare tumours of connective tissue. The exact overall incidence of sarcomas is unknown due to diagnostic difficulties and the various histological subtypes (over 80 subtypes). However, the apparent increasing incidence of sarcomas suggests environmental causes such as pesticides. Except for some specific factors (ie, ionising radiation, vinyl chloride, dioxin and genetic predispositions) the scientific knowledge on the aetiology of sarcomas is sparse and inconsistent. France is a particularly appropriate country to set up a study investigating the causes of sarcoma occurrence due to the French organisation in treatment and care of sarcoma patients, which is highly structured and revolved around national expert networks. The main objective of the ETIOlogy of SARcomas (ETIOSARC) project is to study the role of lifestyle, environmental and occupational factors in the occurrence of sarcomas among adults from a multicentric population-based case-control study. METHODS AND ANALYSIS: Cases will be all incident patients (older than 18 years) prospectively identified in 15 districts of France covered by a general population-based cancer registry and/or a reference centre in sarcoma's patient care over a 3-year period with an inclusion start date ranging from February 2019 to January 2020 and histologically confirmed by a second review of the diagnosis. Two controls will be individually matched by sex, age (5 years group) and districts of residence and randomly selected from electoral rolls. A standardised questionnaire will be administered by a trained interviewer in order to gather information about occupational and residential history, demographic and socioeconomic characteristics and lifestyle factors. At the end of the interview, a saliva sample will be systematically proposed. This study will permit to validate or identify already suspected risk factors for sarcomas such as phenoxyherbicides, chlorophenol and to generate new hypothesis to increase our understanding about the genetic and environmental contributions in the carcinogenicity process. ETHICS AND DISSEMINATION: The present study is promoted by the French National Institute of Health and Medical Research (identification number C17-03). This study received National French Ethic committee (CPP Sud Méditerrannée I) approval (identification number 18-31) and French Data Protection Authority (CNIL) approval (identification number 918171). Results of this study will be published in international peer-reviewed journals. Technical appendix, statistical code and dataset will be available in the Dryad repository when collection data are completed. TRIAL REGISTRATION NUMBER: NCT03670927.

LUCSO-1-French pilot study of LUng Cancer Screening with low-dose computed tomography in a smokers population exposed to Occupational lung carcinogens: study protocol.

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.

3-Dimensional Quantification of Composite Pleural Plaque Volume in Patients Exposed to Asbestos Using High-resolution Computed Tomography: A Validation Study.

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.

Agreement in Occupational Exposures Between Men and Women Using Retrospective Assessments by Expert Coders.

Objectives: To estimate the level of agreement and identify notable differences in occupational exposures (agents) between men and women from retrospective assessments by expert coders. Methods: Lifetime occupational histories of 1657 men and 2073 women from two case-control studies, were translated into exposure estimates to 243 agents, from data on 13882 jobs. Exposure estimates were summarized as proportions and frequency-weighted intensity of exposure for 59 occupational codes by sex. Agreement between metrics of exposure in men's and women's jobs was determined with intraclass correlation coefficients (ICC) and weighted Kappa coefficients, using as unit of analysis ('cell') a combination of occupational code and occupational agent. 'Notable' differences between men and women were identified for each cell, according to a Bayesian hierarchical model for both proportion and frequency-weighted intensity of exposure. Results: For cells common to both men and women, the ICC for continuous probability of exposure was 0.84 (95% CI: 0.83-0.84) and 7.4% of cells showed notable differences with jobs held by men being more often exposed. A weighted kappa of 0.67 (95% CI: 0.61-0.73) was calculated for intensity of exposure, and an ICC of 0.67 (95% CI: 0.62-0.71) for frequency-weighted intensity of exposure, with a tendency of higher values of exposure metrics in jobs held by men. Conclusions: Exposures were generally in agreement between men and women. Some notable differences were identified, most of them explained by differential sub-occupations or industries or dissimilar reported tasks within the studied occupations.