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.

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.

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.

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.

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.

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.

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

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

Cost-Effectiveness of an Organized Lung Cancer Screening Program for Asbestos-Exposed Subjects.

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

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

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

Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis?

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.

Does asbestos exposure cause airway obstruction, in the absence of confirmed asbestosis?

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.

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

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

Exposure to pesticides in open-field farming in France.

OBJECTIVES: Identification of parameters associated with measured pesticide exposure of farmers in open-field farming in France. METHODS: Open-field volunteer farmers were monitored during 1 day use of the herbicide isoproturon on wheat and/or barley during the winters 2001 (n = 9) or 2002 (n = 38) under usual conditions of work. The whole-body method was used to assess potential dermal exposure using coveralls and cotton gloves. Mixing-loading and application tasks were assessed separately with 12 different body areas (hands, arms, forearms, legs, chest, back and thighs) measured for each task (mixing-loading and application separately). RESULTS: Daily potential dermal exposure to isoproturon ranged from 2.0 to 567.8 mg (median = 57.8 mg) in 47 farmers. Exposure during mixing-loading tasks accounted for 13.9-98.1% of the total exposure (median = 74.8%). For mixing-loading, hands and forearms were the most contaminated body areas accounting for an average of 64 and 14%, respectively. For application, hands were also the most contaminated part of the body, accounting for an average of 57%, and thighs, forearms and chest or back were in the same range as one another, 3-10%. No correlations were observed between potential dermal exposure and area sprayed, duration of spraying or size of the farm. However, a significant relationship was observed between exposure and the type of spraying equipment, with a rear-mounted sprayer leading to a higher exposure level than trailer sprayers. Technical problems, particularly the unplugging of nozzles, and the numbers mixing-loading or application tasks performed were also significantly related with higher levels of exposure. CONCLUSIONS: The main results obtained in this study on a large number of observation days are as follows: (i) the mixing-loading step was the most contaminated task in open field accounting for two-thirds of the total daily exposure, (ii) no positive correlation was noted with classically used pesticide-related parameters: farm area, area sprayed and duration of application and (iii) relevant parameters were the type of spraying equipment, the type and number of tasks and technical problems or cases of overflowing.

Factors associated with cancer distress in the Asbestos Post-Exposure Survey (APEXS).

OBJECTIVES: CT-scan screening programs for lung cancer detection have been proposed in high-risk subjects, and more recently in former asbestos-exposed subjects. However, to date no data are available on psychological impact of such programs. The aim of this study is to examine the risk factors of psychological distress at baseline of a CT-scan screening program among asbestos-exposed subjects. METHODS: The Asbestos Post-Exposure Survey (APEXS) was carried out in France between October 2003 and December 2005 in order to screen asbestos-related diseases by CT-scan. Volunteers underwent self-administered questionnaires including an asbestos exposure assessment and, for a large sub-sample, a validated psychological distress scale. Non-exposed subjects were used as reference group. RESULTS: At baseline, a significant higher level of distress was observed in exposed subjects (n = 3,122) relative to the reference group (n = 486) after adjustment on age, sex, and tobacco status. This distress is associated independently with the self-perception of (i) intensity of asbestos exposure and (ii) the risk of current or future disease related to the asbestos exposure. The perception of the cancer risk related to asbestos seems to play a fundamental role in this psychological distress. CONCLUSION: In this study, asbestos-exposed subjects experienced a higher significant cancer distress than previously described in literature. These findings may be of potential public health importance. First, the impact of such occupational exposures on quality of life of patients who suffer from cancer related to these exposures has to be appraised. Secondly, the assessment of psychological impact of CT-scan screening programs among asbestos-exposed subjects is also required.

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

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

Phenotypes of lung cancer and statistical interactions between tobacco smoking and occupational exposure to asbestos and crystalline silica from a large case-only study: The CaProMat study.

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.

Occupational Asbestos Exposure and Incidence of Colon and Rectal Cancers in French Men: The Asbestos-Related Diseases Cohort (ARDCo-Nut).

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.

Factors associated with early-stage pulmonary fibrosis as determined by high-resolution computed tomography among persons occupationally exposed to asbestos.

OBJECTIVES: Asbestosis remains difficult to diagnose, particularly in its early stages. The aim of this study was to determine criteria for independently associated features of pulmonary fibrosis in high-resolution computed tomograms among persons occupationally exposed to asbestos. METHODS: Retired persons with documented occupational asbestos exposure and no known asbestos-related diseases were assessed for occupational, clinical, functional respiratory, and chest X-ray criteria. In addition, they all underwent high-resolution computed tomography (HRCT) in the prone position. RESULTS: Altogether 51 (7.2%) of the 706 enrolled participants had features of pulmonary fibrosis consistent with asbestosis in the HRCT. Among those with small irregular opacities of <1/0 according to the 1980 International Labour Office Classification (ILO-C) in their X-rays, 5% had asbestosis in the HRCT. In a multivariate analysis, only age [odds ratio (OR) per year 1.08, 95% confidence interval (95% CI) 1.02-1.14], cumulative-exposure index (CEI) for asbestos (OR 6.4, 95% CI 1.5-28.4 for a CEI of > or =100 fibers/ml x years), and the presence of small irregular X-ray opacities of > or =1/0 ILO-C (OR 3.0, 95% CI 1.6-6.0) were independently associated with HRCT asbestosis. No combinations of these criteria simultaneously yielded high sensitivity and specificity for the diagnosis of early-stage HRCT asbestosis. Moreover, only 2% of the persons with a CEI of <25 fibers/ml x years had HRCT asbestosis, the finding confirming the low incidence of asbestosis for such low exposure, as previously reported on the basis of X-ray data. CONCLUSIONS: Additional research is needed to better identify the persons most likely to benefit from HRCT screening for asbestosis.

Pleural plaques and the risk of pleural mesothelioma.

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.