Relationships between asbestos exposure and pleural plaques: dose and time effects using fractional polynomials.

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.

Maternal occupational exposure to carbonaceous nanoscale particles and neurodevelopmental outcomes in early childhood: Analysis of the French Longitudinal Study of Children - Elfe study.

OBJECTIVE: To investigate the association between occupational exposures to carbonaceous unintentionally emitted nanoscale particles (UNPs) during pregnancy and the child's language development and behaviour at two years old. METHODS: Using data from the French Longitudinal Study of Childhood - ELFE, we selected mothers who worked during pregnancy and their children. Exposure to carbonaceous UNPs was assessed by the MatPUF (job-exposure matrix for ultrafine particles). Children's lexical development was analysed using 'the Mac Arthur - Bates communicative development inventories-words and sentences-short form' (MB-CDI) in a multivariate binary logistic regression. Their risk for autism spectrum disorders was studied using 'the Modified-CHecklist for Autism in Toddler' (M-CHAT) according to the recommended thresholds (low risk = 0-2; intermediate risk = 3-6 and high risk = 7-23) in unordered multinomial logistic regression models. RESULTS: Maternal occupational exposure to carbonaceous UNPs was associated with delayed child language development (ORadj: 1.34; 95 % CI: 1.00, 1.80) but not with behavioural disorders (autism spectrum disorders) at two years old. CONCLUSION: This is the first epidemiological study to show a significant association between maternal occupational exposure to carbonaceous nanoscale particles and child language development at 2 years old.

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.

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.

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.

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.

Prevalence of occupational exposure to asbestos and crystalline silica according to phenotypes of lung cancer from the CaProMat study: A case-only study.

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.

Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions.

BACKGROUND: Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. METHODS: Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case-control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. RESULTS: Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. CONCLUSION: There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco smoking.

Cancer of the esophagus and asbestos exposure.

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.

Five years update on relationships between malignant pleural mesothelioma and exposure to asbestos and other elongated mineral particles.

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.

Asbestos exposure, pleural plaques, and the risk of death from lung cancer.

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.

Air pollution and activation of mobile medical team for out-of-hospital cardiac arrest.

BACKGROUND: The association between air pollution exposure and cardiovascular events is well established, and the effect of short-term exposure on out-of-hospital cardiac arrest (OHCA) has received some attention. The effect of air pollution exposure and the activation of mobile intensive care units (MICUs) for cardiac arrest have never been studied. OBJECTIVE: We analyzed associations between air pollutants and MICU activation for OHCA. METHOD: This is a retrospective study including 4558 patients with OHCA and MICU activation from 2007 to 2012. A time-stratified case crossover design was used. Particulate matter (PM) of median aerodynamic diameter less than 2.5 µm (PM2.5), less than 10 µm, and ozone were the 3 main pollutants used to determine the effects of pollution exposure on the event. RESULTS: A daily average increase of 27.6 µg/m(3) in ozone was associated with an increase of MICU activation for OHCA the following day (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03-1.22). For women, a daily average increase of 27.6 µg/m(3) in ozone was associated with an increase of MICU activation for OHCA the following day (OR, 1.19; 95% CI, 1.01-1.37). An hourly average increase of 10.5 µg/m(3) in PM2.5 was associated with an increase of MICU activation for OHCA in the current hour (OR, 1.11; 95% CI, 1.02-1.19). For men, an increase in PM2.5 was associated with an increase in MICU activation for OHCA the current hour (OR, 1.10; 95% CI, 1.01-1.20). No association was found with PM of median aerodynamic diameter less than 10 µm. CONCLUSION: An association was found between air pollution and MICU activation for OHCA (ozone and PM2.5).

Perspectives in Biological Monitoring of Inhaled Nanosized Particles.

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

The impact of allergic rhinitis on the management of asthma in a working population.

BACKGROUND: Currently, little data is available about the management of asthma in the working population. The aim of this study was to describe asthma control and severity among workers according to current or previous allergic rhinitis comorbidity. METHODS: A network of occupational physicians participated in this pilot study on a voluntary basis. They included a random sample of salaried workers during their systematic occupational medical check-up. All subjects completed a self-administered questionnaire based on the European Community Respiratory Health Survey screening questionnaire, and if they reported any respiratory symptoms including allergic rhinitis, the physician filled in a medical questionnaire. Current asthma control and severity were evaluated according to 2006 Global Initiative for Asthma guidelines. RESULTS: A total of 110 occupational physicians from two French regions participated. Out of the 6906 employees screened, 3102 identified respiratory symptoms and completed the medical questionnaire and performed spirometry. Overall, 374 were identified as current asthmatics, including 271 (72.5%) with allergic rhinitis. Among current asthmatics with current allergic rhinitis (n = 95), 68.8% had partially controlled asthma or uncontrolled asthma, including 51.6% who received insufficient anti-asthmatic treatment. Partly or no control asthma was not associated with current rhinitis (OR = 1.4; 95% CI: 0.8-2.7). Current asthmatics with current or previous allergic rhinitis had a significantly lower risk of emergency department visits than current asthmatics without allergic rhinitis (respectively 11.6, 17.1 and 29.1%; P = 0.002). CONCLUSIONS: Most current asthmatics both with and without allergic rhinitis had uncontrolled asthma, with inappropriate treatment. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace.

EV@LUTIL: An open access database on occupational exposures to asbestos and man-made mineral fibres.

OBJECTIVES: The aim of Evalutil is to document occupational exposure to asbestos and man-made mineral fibers. METHODS: These databases provide grouped descriptive and metrological data from observed situations of occupational exposure, collected through the analysis of scientific articles and technical reports by industrial hygienists. RESULTS: Over 5,000 measurements were collected. We describe the occupations, economic activities, fiber-containing products, and operations on them that have been documented most often. Graphical measurement syntheses of these data show that the situations presented for asbestos and RCF, except mineral wools, report fiber concentrations mainly above historical occupational exposure limits. CONCLUSION: Free access to these data in French and in English on the Internet (https://ssl2.isped.u-bordeaux2.fr/eva_003/) helps public health and prevention professionals to identify and characterize occupational exposures to fibers. Extended recently to nanoscale particles, Evalutil continues to contribute to the improvement of knowledge about exposure to inhaled particles and the health risks associated with them.

French firefighter mortality: analysis over a 30-year period.

OBJECTIVE: To explore mortality of French professional male firefighters. METHODS: Standardized mortality ratios (SMR) were calculated for 10,829 professional male firefighters employed in 1979 and compared with the French male population between 1979-2008. Firefighters were identified from 89 French administrative departments (93% of population). RESULTS: One thousand six hundred forty two deaths were identified, representing significantly lower all-cause mortality than in the general population (SMR = 0.81; 95%CI: 0.77-0.85). SMR increased with age and was not different from 1 for firefighters >70 years. No significant excess of mortality was observed for any specific cause, but a greater number of deaths than expected were found for various digestive neoplasms (rectum/anus, pancreas, buccal-pharynx, stomach, liver, and larynx). CONCLUSION: We observed lower all and leading-cause mortality likely due to the healthy worker effect in this cohort, with diseases of the respiratory system considerably lower (SMR = 0.57). Non-significant excesses for digestive neoplasms are notable, but should not be over-interpreted at this stage.

Co-exposure to refractory ceramic fibres and asbestos and risk of pleural mesothelioma.

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.

Inter-reader agreement in HRCT detection of pleural plaques and asbestosis in participants with previous occupational exposure to asbestos.

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.