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Background: Ultrafine particles are present in ever greater quantities in the workplace and only one epidemiological study to date has found an association with the occurrence of lung cancer., Objective: To investigate the effect of occupational exposure to ultrafine particles on the risk of lung cancer., Methods: The ARDCO is a surveillance program involving retiree workers who had been exposed to asbestos during their working life. Exposure to ultrafine particles over the complete lifetime occupational history was assessed using the French job exposure matrix MATPUF. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI)., Results: There was no association between exposure to ultrafine particles and lung cancer after adjustment for smoking and exposure to asbestos and crystalline silica., Conclusion: The findings do not indicate increased risks of lung cancer for UFP after adjustment for level of exposure to asbestos, crystalline silica, and smoking status., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the hospital ethics committee (CCPPRB Paris-Cochin n° 1946 2002), CCP Ile-de-France III, no 1946/11/02–02 (2010)). All participants received information on the study and provided their written informed consent. Participants gave informed consent to participate in the study before taking part. All study procedures were performed in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The aim of this study was to analyse the incidence and mortality from various digestive cancer sites and their potential link with pleural plaques, in a French cohort of workers previously occupationally exposed to asbestos., Methods: We conducted a 10-year follow-up study in 13,481 male subjects, included in the cohort between October 2003 and December 2005, for whom asbestos exposure was assessed by calculation of a cumulative exposure index (CEI) in equivalent fibres.years/mL for each subject. We conducted an incidence study and a mortality study. Complementary analysis was restricted to men who had performed at least one chest CT-scan (N = 4,794). We used a Cox model with age as the time axis variable, adjusted for smoking, time since first exposure (TSFE), CEI to asbestos and the existence of pleural plaques on CT-scan., Results: In the incidence study, a significant dose-response relationship was observed between CEI to asbestos and oesophageal cancer (HR 1.03, 95% CI [1.01-1.06]) in the entire cohort after adjustment for TSFE and smoking status. In subjects undergoing CT-scan, a significant association between pleural plaques was observed for oesophageal cancer incidence (HR 2.80, 95% CI [1.09-7.20]) and in the mortality study, multivariate analyses showed a significant dose-effect response between CEI to asbestos and death from oesophageal cancer (HR 1.03, 95% CI [1.00-1.05]) in the entire cohort., Conclusions: This large-scale study confirms results concerning a likely relationship between asbestos exposure and oesophageal cancer, and the association between this cancer and pleural plaques after adjustment on CEI to asbestos., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the hospital ethics committee (CCPPRB Paris-Cochin n°1946 (2002), CCP Ile-de-France III, n°1946/11/02–02 (2010)). All participants received information on the study and provided their written informed consent. all experiments were performed in accordance with relevant guidelines and regulations. Consent for publication: “Not Applicable”. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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.)

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: 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.

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.)

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.

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.)

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.

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.

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.)

The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose-response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose-response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9-3.4) for subjects exposed to 75 fibres · mL(-1) · year(-1) in group 1 increasing to 12.4 (95% CI 4.6-33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF., (©ERS 2014.)

The fibrogenicity and carcinogenicity of asbestos fibers are dependent on several fiber parameters including fiber dimensions. Based on the WHO (World Health Organization) definition, the current regulations focalise on long asbestos fibers (LAF) (Length: L ≥ 5 μm, Diameter: D < 3 μm and L/D ratio > 3). However air samples contain short asbestos fibers (SAF) (L < 5 μm). In a recent study we found that several air samples collected in buildings with asbestos containing materials (ACM) were composed only of SAF, sometimes in a concentration of ≥10 fibers.L-1. This exhaustive review focuses on available information from peer-review publications on the size-dependent pathogenetic effects of asbestos fibers reported in experimental in vivo and in vitro studies. In the literature, the findings that SAF are less pathogenic than LAF are based on experiments where a cut-off of 5 μm was generally made to differentiate short from long asbestos fibers. Nevertheless, the value of 5 μm as the limit for length is not based on scientific evidence, but is a limit for comparative analyses. From this review, it is clear that the pathogenicity of SAF cannot be completely ruled out, especially in high exposure situations. Therefore, the presence of SAF in air samples appears as an indicator of the degradation of ACM and inclusion of their systematic search should be considered in the regulation. Measurement of these fibers in air samples will then make it possible to identify pollution and anticipate health risk.

Objectives: To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure., Methods: A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression., Results: A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs. 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI -33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women., Conclusions: Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women., (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.)

We analyze the effect of occupational exposure to asbestos on the occurrence of lung cancer based on a recent French case-control (CC) study. We build a large collection of threshold regression models, data-adaptively select a better model by CC-weighted likelihood-based cross-validation and then fit this better model by CC-weighted maximum likelihood. The CC-weighting allows us to draw valid inferences from CC data without relying on a logistic regression. This is possible because the joint distribution of the indicator of being a case and matching variable is available beforehand owing to two studies independent from our data set. The implications of the fitted model in terms of years of life free of lung cancer lost due to the exposure to asbestos are discussed.

Background: More than 80% of mesothelioma cases in men are attributable to occupational asbestos exposure compared to only 40% in women. The objective of the study was to characterize a series of female pleural mesotheliomas according to known and suspected risk factors., Methods: From the exhaustive recording of 318 female mesothelioma cases in the French National Mesothelioma Surveillance Program between 1998 and 2009, multiple correspondence analysis and hybrid clustering were performed to characterize these cases according to expert assessed occupational and non-occupational exposure to asbestos and man-made vitreous fibers, X-ray exposure, and history of cancer and non-malignant respiratory diseases., Results: Four clusters were identified: (1) occupational exposure to asbestos and man-made vitreous fibers (7.9% of subjects); (2) radiation exposure during radiotherapy (12.9%); (3) increased asbestos exposure (19.8%); and (4) "non-exposure" characteristics (59.4%)., Conclusion: These results will allow hypotheses to be generated about associations between mesothelioma and non-occupational asbestos exposure, X-ray exposure and history of respiratory disease., (Copyright © 2013 Wiley Periodicals, Inc.)

Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.

Background: The association between pleural plaques and pleural mesothelioma remains controversial. The present study was designed to examine the association between pleural plaques on computed tomography (CT) scan and the risk of pleural mesothelioma in a follow-up study of asbestos-exposed workers., Methods: Retired or unemployed workers previously occupationally exposed to asbestos were invited to participate in a screening program for asbestos-related diseases, including CT scan, organized between October 2003 and December 2005 in four regions in France. Randomized, independent, double reading of CT scans by a panel of seven chest radiologists focused on benign asbestos-related abnormalities. A 7-year follow-up study was conducted in the 5287 male subjects for whom chest CT scan was available. Annual determination of the number of subjects eligible for free medical care because of pleural mesothelioma was carried out. Diagnosis certification was obtained from the French mesothelioma panel of pathologists. Survival regression based on the Cox model was used to estimate the risk of pleural mesothelioma associated with pleural plaques, with age as the main time variable and time-varying exposure variables, namely duration of exposure, time since first exposure, and cumulative exposure index to asbestos. All statistical tests were two-sided., Results: A total of 17 incident cases of pleural mesothelioma were diagnosed. A statistically significant association was observed between mesothelioma and pleural plaques (unadjusted hazard ratio (HR) = 8.9, 95% confidence interval [CI] = 3.0 to 26.5; adjusted HR = 6.8, 95% CI = 2.2 to 21.4 after adjustment for time since first exposure and cumulative exposure index to asbestos)., Conclusion: The presence of pleural plaques may be an independent risk factor for pleural mesothelioma.

Background: Underreporting of occupational diseases related to asbestos exposure remains a matter of concern in France. The aim of this study was to evaluate the number of claims for compensation for asbestos-related non-malignant pulmonary or pleural occupational disease in subjects having undergone a chest CT-scan in a multiregional screening programme., Methods: Among the 5444 voluntary retired asbestos-exposed subjects recruited in four regions between 2003 and 2005 who had undergone a chest CT-scan, the number of claims for compensation for an asbestos-related pulmonary or pleural benign disease was analysed in 2006 and 2010., Results: Following CT-scan screening, 17.2% of participants were acknowledged as presenting with an asbestos-related non-malignant occupational disease, essentially pleural plaques, by the French National Health Insurance fund. Underreporting decreased as duration of follow-up after CT-scan increased. Nevertheless, 4 years after CT-scan, underreporting was still as high as 36% for subjects identified as presenting with pleural plaques. Mean duration between the date of CT-scan and the date of recognition as occupational disease was 7.4 months, shorter in cases where screening was coordinated by specialized centres., Conclusion: A plan of action for an easier claiming process for compensation of asbestos-related diseases is desired. This could probably be obtained through improved sensitization of physicians engaged in the follow-up of asbestos-exposed subjects, and by standardization of the interpretation and reporting of asbestos-related abnormalities observed on chest CT-scans., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objectives: The hypothesis that asbestos exposure may have more specific associations with particular histological types of lung cancer remains controversial. The aim of this study was to analyze the relationships between asbestos exposure and pulmonary carcinoid tumors., Methods: A retrospective case-control study was conducted in 28 cases undergoing surgery for pulmonary carcinoid tumors and aged >40 years and in 56 controls with lung cancer of a different histological type, matched for gender and age, from 1994 to 1999, recruited in two hospitals in the region of Paris. Asbestos exposure was assessed via expertise of a standardized occupational questionnaire and mineralogical analysis of lung tissue, with quantification of asbestos bodies (AB)., Results: Definite asbestos exposure was identified in 25% of cases and 14% of controls (ns). Cumulative asbestos exposure was significantly higher in cases than in controls (P < 0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and 9% had >1000 AB per gram dry lung tissue, respectively, P = 0.09). Mean cumulative smoking was lower in cases than in controls (P < 0.05)., Conclusions: This study argues in favor of a relationship between asbestos exposure and certain pulmonary carcinoid tumors.

Background: In the course of setting up the National Mesothelioma Surveillance Program (PNSM), established in France in 1998, the question arose as to the most suitable method of assessing occupational exposure. The aim of this study was to define the most suitable rating method for assessing occupational asbestos exposure in order to assess medico-social care., Method: The study included 100 subjects-50 cases of mesothelioma and 50 controls-randomly selected and representing 457 jobs held. Job asbestos exposure was assessed by a six-expert panel using two methods: "by job" rating, where all the jobs in were assessed regardless of the subjects; and "by subject" rating, where all the jobs of a subject were assessed at the same time. Consensus was obtained and subjects' exposure was calculated for each rating. Then, two internal experts assessed job asbestos exposure with the "by subject" rating. Kappa coefficients were used to measure agreement between the ratings., Results: Agreement between "by job" and "by subject" ratings was very good for subject probability of exposure (kappa = 0.84) and cumulative exposure index (kappa = 0.80). Agreement between the six-expert panel and the two internal experts was good for subject exposure (kappa for probability = 0.71; kappa for cumulative exposure index= 0.68)., Conclusion: This study shows that the two rating systems have good or very good agreement. These results validate the routine use in the PNSM of the "by subject" rating, with the advantage of being convenient and quick to provide feedback on occupational asbestos exposure to mesothelioma cases for compensation., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics., Methods: The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques., Results: Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques., Conclusions: The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Objective: To analyse the relationship between pulmonary nodules detected by radiologists using computed tomography and cumulative exposure to asbestos or asbestos-related pleuro-pulmonary diseases in 5662 asbestos-exposed subjects, and the relationship between pulmonary nodules and thoracic cancer, to determine whether a specific surveillance strategy based on cumulative asbestos exposure should be adopted., Design: Standardised incidence and mortality ratios (SIR) for lung cancer and pleural mesothelioma were calculated in patients with and without mention of pulmonary nodules and compared using comparative morbidity figures., Results: A significant excess incidence of primary lung cancer and pleural mesothelioma was observed among subjects presenting with pulmonary nodule(s) (SIR respectively 1.95, 95%CI 1.22-2.95, and 11.88, 95%CI 3.20-30.41). However, there was no significant relationship between pulmonary nodules mentioned by radiologists and cumulative asbestos exposure or between pulmonary nodules and the presence of asbestos-related benign diseases., Conclusions: This study confirms the expected excess prevalence of lung cancer in subjects presenting with pulmonary nodules according to the radiologist's report, and shows the absence of relationship between the presence of nodules and level of cumulative asbestos exposure. Our study therefore offers no argument in favour of specific surveillance modalities based on estimated cumulative asbestos exposure.

Background: It is uncertain whether isolated pleural plaques cause functional impairment., Objective: To analyse the relationship between isolated pleural plaques confirmed by CT scanning and lung function in subjects with occupational exposure to asbestos., Methods: The study population consisted of 2743 subjects presenting with no parenchymal interstitial abnormalities on the high-resolution CT (HRCT) scan. Asbestos exposure was evaluated by calculation of an individual cumulative exposure index (CEI). Each subject underwent pulmonary function tests (PFTs) and HRCT scanning. Variables were adjusted for age, smoking status, body mass index, CEI to asbestos and the centres in which the pulmonary function tests were conducted., Results: All functional parameters studied were within normal limits for subjects presenting with isolated pleural plaques and for those presenting with no pleuropulmonary abnormalities. However, isolated parietal and/or diaphragmatic pleural plaques were associated with a significant decrease in total lung capacity (TLC) (98.1% predicted in subjects with pleural plaques vs. 101.2% in subjects free of plaques, p=0.0494), forced vital capacity (FVC) (96.6% vs. 100.4%, p<0.001) and forced expiratory volume in 1 s (FEV(1)) (97.9% vs. 101.9%, p=0.0032). In contrast, no significant relationship was observed between pleural plaques and FEV1/FVC ratio, forced expiratory flow at 25-75% FVC and residual volume. A significant correlation was found between the extent of pleural plaques and the reduction in FVC and TLC, whereas plaque thickness was not related to functional impairment., Conclusions: The results show a relationship between isolated parietal and/or diaphragmatic pleural plaques and a trend towards a restrictive pattern, although the observed decrease in FVC and TLC is unlikely to be of real clinical relevance for the majority of subjects in this series.

A link between the inhalation of asbestos fibres and the outcome of benign and malignant respiratory diseases has been established from numerous epidemiological data in occupational settings. Occupational exposure limit values have been established with a gradual lowering of these over time. Conversely, there are few epidemiological data dealing with exposure in the indoor environment. However, numerous materials and products containing asbestos (MPCA) are present in the indoor environment, due to their widespread use in the construction sector in the years between 1960 and 1990. The regulations were changed from the late 1990s, leading to a systematic inventory of the presence of asbestos-containing materials in buildings. The aim of this manuscript is to clarify the different types of MPCA encountered in the indoor environment, to describe the techniques used to highlight asbestos depending on the nature of the materials, the regulatory requirements relating to asbestos in non-occupational situations, and to update on the state of knowledge on asbestos-related diseases in the indoor environment., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The relationships between benign asbestos-related diseases (asbestosis and pleural plaques) and thoracic cancers are still debated. The aim of this paper was to review the epidemiological data relevant to this issue., Current Knowledge: Published studies show a significant relationship between occupational exposure to asbestos and lung cancer risk, even in the absence of abnormalities consistent with asbestosis on the postero-anterior chest x-ray. For a given cumulative asbestos exposure, the presence of radiographic evidence of asbestosis is associated with an increased risk of lung cancer. Among asbestos-exposed individuals, those having radiographic evidence of pleural plaques are at increased risk for lung cancer and pleural mesothelioma, compared to the general population. However, there is no evidence that pleural plaque confers an increased risk of lung cancer or pleural mesothelioma within a population of individuals having the same cumulative asbestos exposure., Perspectives: The studies identified for this review relied only on chest radiograph data. Studies involving accurate evaluations of asbestos exposure and computed tomography of the chest are needed., Conclusion: Currently available data indicate that patient follow-up modalities should be dictated solely by the estimated cumulative asbestos exposure and not by the existence of pleural plaques., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Occupational exposure to asbestos, widely used in various industries for decades, is the most important risk factor for pleural mesothelioma. We report here the ranking of occupations and industries in France at high risk for this cancer among men and women., Methods: A population-based case-control study, conducted from 1998 to 2002, included 462 cases (80.3% men) and 897 controls. Data were collected in face-to-face interviews with a standardized questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each occupation and industry; subjects never employed in each category were the reference., Results: For men, risks were high for several occupations and industries. Besides the expected high risks for non-metallic mineral product makers and manufacturing asbestos products, occupations such as plumbers (OR = 5.57, 95% CI: 2.90-10.69), sheet-metal workers, welders, metal molders, coremakers, and cabinetmakers were also at high risk. Elevated risks were found in the industries of shipbuilding (OR = 9.13, 95% CI: 5.20-16.06) and construction, but also in the manufacturing of metal products, chemicals, and railroad and aircraft equipment. The results for women showed increased but not significant risks in several occupational activities., Conclusions: This report provides new insight into the epidemiology of mesothelioma, confirming risks for occupational activities reported earlier and pointing out risks in activities never previously reported. It offers guidance to authorities for the compensation of asbestos victims and for prevention in at-risk activities still involving asbestos-containing products.

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

Background: The aim of this study was to assess the psychological consequences of HRCT scan screening in retired asbestos-exposed workers., Methods: A HRCT-scan screening program for asbestos-related diseases was carried out in four regions of France. At baseline (T1), subjects filled in self-administered occupational questionnaires. In two of the regions, subjects also received a validated psychological scale, namely the psychological consequences questionnaire (PCQ). The physician was required to provide the subject with the results of the HRCT scan at a final visit. A second assessment of psychological consequences was performed 6 months after the HRCT-scan examination (T2). PCQ scores were compared quantitatively (t-test, general linear model) and qualitatively (chi²-test, logistic regression) to screening results. Multivariate analyses were adjusted for gender, age, smoking, asbestos exposure and counseling., Results: Among the 832 subjects included in this psychological impact study, HRCT-scan screening was associated with a significant increase of the psychological score 6 months after the examination relative to baseline values (8.31 to 10.08, p < 0.0001, t-test). This increase concerned patients with an abnormal HRCT-scan result, regardless of the abnormalities, but also patients with normal HRCT-scans after adjustment for age, gender, smoking status, asbestos exposure and counseling visit. The greatest increase was observed for pleural plaques (+3.60; 95%CI [+2.15;+5.06]), which are benign lesions. Detection of isolated pulmonary nodules was also associated with a less marked but nevertheless significant increase of distress (+1.88; 95%CI [+0.34;+3.42]). However, analyses based on logistic regressions only showed a close to significant increase of the proportion of subjects with abnormal PCQ scores at T2 for patients with asbestosis (OR = 1.92; 95%CI [0.97-3.81]) or with two or more diseases (OR = 2.04; 95%CI [0.95-4.37])., Conclusion: This study suggests that HRCT-scan screening may be associated with increased distress in asbestos-exposed subjects. If confirmed, these results may have consequences for HRCT-scan screening recommendations.

Rationale: Whether occupational exposure to asbestos causes airway obstruction remains controversial., Objectives: This study evaluated lung function in relation to cumulative exposure to asbestos in a large cohort of retired or unemployed workers exposed to asbestos., Methods: The study population consisted of 3,660 volunteer subjects. An individual cumulative exposure index to asbestos was calculated for each subject, and information was obtained on smoking status. Pulmonary function tests were performed in all subjects; high-resolution chest computed tomography was also performed in 3,335 subjects., Measurements and Main Results: Values of FEV(1)/FVC and FEF(25-75%) did not differ between five classes (quintiles) of cumulative exposure to asbestos, and no significant correlation was observed between cumulative exposure to asbestos and pulmonary function parameters, after adjustment for sex, tobacco consumption, emphysema, and body mass index. Furthermore, the proportion of abnormal pulmonary function tests did not differ between the five classes of cumulative exposure to asbestos., Conclusions: The results do not support a causal relationship between asbestos exposure alone and airway obstruction. However, the study sample may not be representative of all people occupationally exposed to asbestos, because a fraction of subjects with previously diagnosed asbestosis probably did not participate in this screening program.

Epidemiological studies have shown that asbestos fibers constitute the major occupational risk factor and that asbestos acts synergistically with tobacco smoking to induce lung cancer. Although some somatic gene alterations in lung cancer have been linked to tobacco smoke, few data are available on the role of asbestos fibers. P16/CDKN2A is an important tumor suppressor gene that is frequently altered in lung cancer via promoter 5'-CpG island hypermethylation and homozygous deletion, and rarely via point mutation. Many studies suggest that tobacco smoking produces P16/CDKN2A promoter hypermethylation in lung cancer, but the status of this gene in relation to asbestos exposure has yet to be determined. The purpose of this study was to investigate the mechanism of P16/CDKN2A alterations in lung cancer in asbestos-exposed patients. P16/CDKN2A gene status was studied in 75 human non-small-cell lung cancer (NSCLC) cases with well-defined smoking habits, and detailed assessment of asbestos exposure, based on occupational questionnaire and determination of asbestos bodies in lung tissue. The results of this study confirm published data on the effect of tobacco smoke on P16/CDKN2A gene alterations, characterized by significantly higher P16/CDKN2A promoter hypermethylation in heavy smokers (more than 40 pack-years (P-Y)) than in smokers of less than 40 P-Y. These results also demonstrate a higher incidence of loss of heterozygosity and homozygous deletion in asbestos-exposed cases, after adjustment for age and cumulative tobacco consumption, than in unexposed cases (P=0.0062). This study suggests that P16/CDKN2A gene inactivation in asbestos-exposed NSCLC cases mainly occurs via deletion, a feature also found in malignant mesothelioma, a tumor independent of tobacco smoking but associated with asbestos exposure, suggesting a possible relationship with an effect of asbestos fibers.

Objectives: Few studies have been carried out to evaluate the respiratory effects of asbestos exposure of custodian and maintenance workers., Methods: By a multicentre cross-sectional study, 277 custodian and maintenance employees working in buildings with friable asbestos-containing materials and 87 unexposed subjects were studied for radiological abnormalities by use of the International Labour Office (ILO) classification of radiographs of pneumoconiosis, in relation to parameters of asbestos exposure., Results: The cumulative asbestos exposure index was generally low (fewer than 5 fibres/ml x years in 82.3% of exposed workers). On multivariate analysis, pleural thickening was significantly related to latency since onset of exposure to asbestos in exposed workers, after adjustment for age, body mass index and tobacco smoking., Conclusions: Asbestos exposure of custodian and maintenance employees in buildings with friable asbestos-containing materials might be associated with an excess of pleural thickening on chest X-rays., (Copyright 2004 Springer-Verlag)

Background: In the literature, the criteria used to define pleural plaques (PP) and diffuse pleural thickening (DPT) are very heterogeneous and often imprecise. A multicenter restropective study was conducted to assess the relevance of two radiographic definitions of DPT., Methods: The study population consisted of 287 subjects with asbestos-related pleural thickening. Two definitions were used to characterize DPT on postero-anterior chest radiographs: definition 1: pleural thickening associated with obliteration of the costophrenic angle; definition 2: pleural thickening at least 5 mm wide, extending for more than one quarter of the chest wall. Prevalence of respiratory symptoms and pulmonary function tests were compared in the DPT and PP groups resulting from the two definitions of DPT., Results: According to definition 1, 34 patients (11.8%) were classified in the DPT group. Prevalence of chronic sputum, dyspnea, and chest pain was significantly higher in this group than in the PP group. FEV(1), FVC, and TLC were significantly lower. The differences persisted after adjustment for confounding factors. According to definition 2,102 patients (36.6%) were classified in the DPT group. DPT and PP groups did not differ in terms of prevalence of respiratory symptoms, or pulmonary function tests. Agreement between readers was significantly better when using definition 1., Conclusions: Obliteration of costophrenic angle is a much more reliable sign than dimensional criteria to characterize DPT., (Copyright 2004 Wiley-Liss, Inc.)

A cross-sectional medical survey including collection of three consecutive sputum samples was carried out among 270 retired workers of a textile and friction materials factory, in order to investigate the relationship between asbestos body identification and asbestos exposure. The individual cumulative asbestos exposure, determined by means of a plant-specific job-exposure matrix based on asbestos air measurements in the workshops, proved to be heavy with a mean cumulative exposure of 217 fibres x mL(-1) x yr. Macrophages and asbestos bodies were identified in sputum samples by light microscopy. The lung origin of the sputum, suggested by the presence of macrophages and/or asbestos bodies, was confirmed in 82.6% of subjects, and 53% of these samples were positive for asbestos bodies. The prevalence of asbestos bodies was not related to sex, smoking status or latency. Conversely, multivariate analysis showed a positive relationship with cumulative exposure, duration and intensity of exposure to asbestos, as well as age and time since retirement. These findings suggest that sputum analysis for asbestos bodies may remain a relevant and noninvasive marker of heavy occupational exposure to asbestos, even years after retirement. Owing to the new perspectives in lung cancer screening, it might contribute to the identification of high-risk subjects.

Despite intrinsic limitations due to differences in the bio-persistence of the various asbestos types, in the definition of control populations and in analytical techniques used by the laboratories, mineralogical analysis of biological samples is useful in the assessment of past exposure to asbestos. It provides additional information to occupational and environmental questionnaires, particularly when exposure to asbestos is doubtful, unknown or forgotten by a subject. Results should be interpreted taking into account clinical information. A positive result does not mean existence of asbestos-related disease. A negative result does not exclude previous significant asbestos exposure, clearly identified by an occupational questionnaire (particularly for exposure to chrysotile). Threshold values indicative of a high probability of previous asbestos exposure have been established for bronchoalveolar lavage fluid (BALF) samples and lung tissue samples. Quantification of asbestos bodies by light microscopy is easy to perform. Sensitivity and specificity of this analysis towards the total pulmonary asbestos fiber burden is good. Therefore this analysis should be performed first. Mineralogical analysis in BALF or lung tissue should be considered only when sampling is supported by diagnostic or therapeutic implications.

Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first.

The application of new decrees concerning the protection of individuals against sanitary risks linked to the various possible expositions to asbestos dusts is leading to a growing involvement of pulmonologists in diagnosis procedures not only for active workers regularly examined via the occupational medicine healthcare system, but also for those who are no longer, the unemployed or retired previously exposed to asbestos fibres. The present chapter presents and comments the revised guidelines about the compensation procedures for occupational diseases, and provides useful recommendations for establishing the records leading to their medical assessment. It emphasises the importance of a close cooperation between pulmonologists and radiologists in order to avoid radiation overdosing, which could increase the risk of lung cancer, as much as possible.

The application of new decrees concerning the protection of individuals against sanitary risks linked to the various possible expositions to asbestos dusts is leading to a growing involvement of pulmonologists in diagnosis procedures not only for active workers regularly examined via the occupational medicine healthcare system, but also for those who are no longer, the unemployed or retired previously exposed to asbestos fibres. The present chapter presents and comments the revised guidelines about the compensation procedures for occupational diseases, and provides useful recommendations for establishing the records leading to their medical assessment. It emphasises the importance of a close cooperation between pulmonologists and radiologists in order to avoid radiation overdosing, which could increase the risk of lung cancer, as much as possible.

A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.

Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first.

A retrospective study was conducted in 23 subjects with previous occupational exposure to asbestos and exhibiting rounded atelectasis (RA) on high-resolution computed tomography scan (HRCT scan) to evaluate the retention of asbestos bodies (ABs) using light microscopy in the bronchoalveolar lavage (BAL) fluid or lung parenchyma in such patients. A total of 31 RAs were identified, usually located in the lower (25 RAs) and posterior (23 RAs) parts of the lung. Pleural thickening in contact with the RA was observed in 27 RAs and parenchymal bands were detected in 15 cases. Twelve of the 20 patients who underwent BAL or surgery exhibited significant retention of ABs in BAL fluid or lung tissue. Moreover, a significant retention of ABs was observed in five of nine patients with a history of asbestos exposure but no diffuse pleural thickening on chest radiograph or interstitial opacities on HRCT scan. Patients with RAs and coexisting diffuse pleural thickening and/or interstitial fibrosis should be considered at a higher risk for lung cancer in comparison to patients with isolated circumscribed pleural plaques based on increased AB counts. By contrast, the excess risk of lung cancer is more questionable in patients with only RAs and circumscribed pleural plaques as they may have AB counts either above or below that associated with pleural plaques alone. This emphasizes the need for further follow-up studies to define criteria indicating the need for thoracotomy in these subjects.