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.

Assessment of lung hyperinflation in occupational chronic obstructive pulmonary disease: a multicentric cross-sectional study.

Occupational exposure is associated with elevated morbidity and lower quality of life in patients with chronic obstructive pulmonary disease (COPD). Static hyperinflation is an independent risk factor for all-cause mortality in COPD and for COPD exacerbation. In a multicentre, cross-sectional study (BPROFETIO), we sought to analyse the relationship between static hyperinflation and occupational exposure in patients with COPD with or without occupational exposure. MATERIAL AND METHODS: An overall 'whole working life' cumulative exposure index was calculated for occupational patients with COPD. Spirometry indices and lung volumes were measured according to the 2005 American Thoracic Society/European Respiratory Society guidelines. RESULTS: After adjustment for age, sex, height, body mass index, smoking and coexposure, the analysis for each occupational hazard showed a higher risk for hyperinflation and FEV1 decline or progression of COPD or GOLD stage for patients with COPD exposed to non-metallic inorganic dusts. CONCLUSION: Occupational exposures should be more investigated in clinical practice and studies as they contribute to the COPD heterogeneity and are associated for some with the development of a static hyperinflation; a condition that is known to have a negative impact on quality of life and survival.

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.

Educational interventions to integrate surgical staff within medical units during the COVID-19 pandemic: EDUCOVID survey.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support. OBJECTIVE: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale. DESIGN: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France. RESULTS: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% (n = 3) and 22% (n = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively. CONCLUSIONS: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

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.

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.

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review.

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

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

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

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

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

Development of a Questionnaire for the Search for Occupational Causes in Patients with Non-Hodgkin Lymphoma: The RHELYPRO Study.

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

Household transmission and incidence of positive SARS-CoV-2 RT-PCR in symptomatic healthcare workers, clinical course and outcome: a French hospital experience.

OBJECTIVES: Although healthcare workers (HCWs) have been particularly affected by SARS-CoV-2, detailed data remain scarce. In this study, we investigated infection rates, clinical characteristics, occupational exposure and household transmission among all symptomatic HCWs screened by SARS-CoV-2 RT-PCR between 17 March (French lockdown) and 20 April. METHODS: SARS-CoV-2 RT-PCR was proposed to symptomatic (new cough or dyspnoea) HCWs at Creteil Hospital in one of the Parisian suburbs most severely affected by COVID-19. Data on occupational profile, living situation and household, together with self-isolation and mask use at home were collected, as well as the number of cases in the household. RESULTS: The incidence rate of symptomatic SARS-CoV-2 was estimated to be 5% (110/2188). A total of 110 (35%) of the 314 HCWs tested positive and 9 (8%) were hospitalised. On multivariate analysis, factors independently associated with positive RT-PCR were occupational profile with direct patient facing (OR 3.1, 95% CI 1.1 to 8.8), p<0.03), and presence of anosmia (OR 5.7, 95% CI 3.1 to 10.6), p<0.0001). Being a current smoker was associated with negative RT-PCR (OR 0.3, 95% CI 0.1 to 0.7), p=0.005). Transmission from HCWs to household members was reported in 9 (14%) cases, and 2 deaths occurred. Overall, self-isolation was possible in 52% of cases, but only 31% of HCWs were able to wear a mask at home. CONCLUSION: This is the first study to report infection rates among HCWs during the peak of the SARS-CoV-2 epidemic in France and the lockdown period, highlighting the risk related to occupational profile and household transmission.

Characterization of chronic obstructive pulmonary disease in dairy farmers.

BACKGROUND: Although farming is often considered a risk factor for COPD, data regarding the burden and characteristics of COPD in dairy farmers are sparse and conflicting. OBJECTIVES: To characterize COPD in dairy farmers. METHODS: 4788 subjects entered two parallel COPD screening programs, one in agricultural workers and one in general practice from 2011 to 2015. Subjects with COPD were invited to participate in the characterization phase of the study. Those who accepted were included in two subgroups: dairy farmers with COPD (DF-COPD) (n = 101) and non-farmers with COPD (NF-COPD) (n = 85). Patients with COPD were frequency-matched with subjects with normal spirometry for age, sex and tobacco smoking (pack-years and status) (DF-controls n = 98, NF-controls n = 89). All subjects from these four groups underwent lung function and exercise testing, questionnaires and blood analysis. RESULTS: The frequency of COPD in dairy farmers was 8.0% using the GOLD criterion and 6.2% using the lower limit of normal criterion and was similar in non-farming subjects (7.3% and 5.2%, respectively) although dairy farmers had lower tobacco consumption (screening phase). DF-COPD had better pulmonary function, exercise capacity and quality of life, fewer symptoms and comorbidities than NF-COPD, and higher levels of some Th2 biomarkers (MCP-2, periostin) (characterization phase). In farmers, COPD was not related to occupational exposure factors, supporting the role of host factors. CONCLUSION: COPD secondary to organic dust exposure (dairy farming) appears less severe and associated with fewer comorbidities than COPD secondary to tobacco smoking.

In Patients with Mild-to-Moderate COPD, Tobacco Smoking, and Not COPD, Is Associated with a Higher Risk of Cardiovascular Comorbidity.

Background: Comorbidities including cardiovascular diseases are very common in chronic obstructive pulmonary disease (COPD) secondary to tobacco smoking and contribute to the overall severity of the disease. In non-smoking COPD, which accounts for about 25% of COPD cases worldwide, current knowledge on the frequency and determinants of comorbidities remains scarce. The aims of the current study were to assess the frequency of major comorbidities and to evaluate their determinants in a group of non-selected patients with mild-to-moderate COPD who were exposed to organic dust (dairy farmers), to tobacco smoking, or to both, and in controls without COPD who were exposed to organic dust (dairy farmers), or to tobacco smoking, or to both, or who were without exposure. Patients and Methods: A total of 4665 subjects (2323 dairy farmers and 2342 non-farmers) including 355 patients with COPD and 4310 controls with normal spirometry were recruited through a large COPD screening program. Self-reported physician-diagnosed diseases with plausible links to COPD were recorded in this cross-sectional study. Results: Whatever the exposure, cardiovascular comorbidities were not more frequent in patients with COPD than their counterparts without airflow limitation. A higher risk of major cardiovascular comorbidities was associated with tobacco smoking and a lower risk was associated with exposure to organic dusts. Conclusion: Tobacco smoking (but not COPD) is associated with higher frequency of cardiovascular comorbidities. By contrast, being a dairy farmer exposed to organic dusts is associated with a lower frequency of the same comorbidities. This reinforces the crucial need for controlling established cardiovascular risk factors even in patients with mild-to-moderate COPD.

Cardiovascular Risk in COPD: Deciphering the Contribution of Tobacco Smoking.

BACKGROUND: The observation that COPD is an independent risk factor for cardiovascular disease (CVDs) comes from comparisons between smokers with COPD and smokers without COPD. The mechanisms that explain increased risk of CVD in patients with COPD are still unclear. OBJECTIVES: The goal of this study was to assess systemic arterial stiffness (a predictor of CVD mortality) and to evaluate its determinants in a group of patients with mild to moderate COPD secondary to organic dust exposure, tobacco smoking, or both. METHODS: Systemic arterial stiffness was assessed by using aortic pulse wave velocity (aPWV). Measurements were made in 142 patients with COPD and 155 healthy control subjects matched for age, sex, BMI, and tobacco smoking, exposed to tobacco smoking (n = 56/70 for COPD/control subjects, respectively), organic dusts (n = 44/48), or both (n = 42/37). RESULTS: aPWV was higher in COPD than in healthy controls in subjects exposed to tobacco smoking and to both organic dusts and tobacco smoking. By contrast, among never smokers exposed to organic dusts, patients with COPD and matched control subjects had similar aPWV. Multivariate analysis of the 142 patients with COPD (exposed to tobacco smoking and/or to organic dusts) showed that tobacco smoking was associated with high aPWV. Moreover, soluble suppression of tumorigenicity 2, a marker of major cardiovascular events, was correlated with aPWV in these patients. CONCLUSIONS: Analysis of an unselected group of patients with COPD with different causes suggests that: (1) COPD by itself is not sufficient to explain increased aPWV; and (2) tobacco smoking is a risk factor for elevated aPWV in COPD.

Is atopy a risk indicator of chronic obstructive pulmonary disease in dairy farmers?

Allergic mechanisms related to environmental and occupational exposure have been suggested to contribute to the development of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To investigate the relationships between atopy markers, persistent airflow limitation (PAL) and occupational exposure in dairy farmers. METHODS: Clinical and biological (total IgE and 21 allergen specific IgE) markers of atopy were assessed in 101 dairy farmers with PAL (DF-PAL), 85 non-farmers with PAL (NF-PAL) (both groups were prospectively included from a screening program performed between 2011 and 2015), and matched controls, i.e. 98 farmers without PAL (DF-controls) and 89 non-farming subjects without PAL (NF-controls). Occupational exposure in farmers was estimated using a validated questionnaire. RESULTS: Prevalence of allergy history was significantly higher in DF-PAL and in NF-PAL than in controls. Polysensitization, and sensitization to seasonal and food allergens were more frequent in DF-PAL than in DF-controls, respectively: 13.8% vs 1% (adjusted odds ratio (aOR): 17.5 (2.2-134), 11.9% vs 3.1% (aOR: 4.4 (1.2-7.2) and 16.8% vs 4.1% (aOR: 5.2 (1.7-7.2)). The prevalence of atopy markers was similar between NF-PAL patients and NF-controls. CONCLUSIONS: PAL in farmers is associated with a high rate of markers of atopy, supporting atopy as a risk indicator. Clinical trial registered with ClinicalTrials.gov (NCT02540408).

Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

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

Respiratory effects of trichloroethylene.

Trichloroethylene (TCE) is a chlorinated solvent that has been used widely around the world in the twentieth century for metal degreasing and dry cleaning. Although TCE displays general toxicity and is classified as a human carcinogen, the association between TCE exposure and respiratory disorders are conflicting. In this review we aimed to systematically evaluate the current evidence for the respiratory effects of TCE exposure and the implications for the practicing clinician. There is limited evidence of an increased risk of lung cancer associated with TCE exposure based on animal and human data. However, the effect of other chlorinated solvents and mixed solvent exposure should be further investigated. Limited data are available to support an association between TCE exposure and respiratory tract disorders such as asthma, chronic bronchitis, or rhinitis. The most consistent data is the association of TCE with autoimmune and vascular diseases such as systemic sclerosis and pulmonary veno-occlusive disease. Although recent data are reassuring regarding the absence of an increased lung cancer risk with TCE exposure, clinicians should be aware of other potential respiratory effects of TCE. In particular, occupational exposure to TCE has been linked to less common conditions such as systemic sclerosis and pulmonary veno-occlusive disease.