Enhancing Diagnostic Capabilities for Occupational Lung Diseases Using LIBS Imaging on Biopsy Tissue.

Laser-induced breakdown spectroscopy (LIBS) imaging continues to gain strength as an influential bioanalytical technique, showing intriguing potential in the field of clinical analysis. This is because hyperspectral LIBS imaging allows for rapid, comprehensive elemental analysis, covering elements from major to trace levels consistently year after year. In this study, we estimated the potential of a multivariate spectral data treatment approach based on a so-called convex envelope method to detect exotic elements (whether they are minor or in trace amounts) in biopsy tissues of patients with occupational exposure-related diseases. More precisely, we have developed an approach called Interesting Features Finder (IFF), which initially allowed us to identify unexpected elements without any preconceptions, considering only the set of spectra contained in a LIBS hyperspectral data cube. This task is, in fact, almost impossible with conventional chemometric tools, as it entails identifying a few exotic spectra among several hundred thousand others. Once this detection was performed, a second approach based on correlation was used to locate their distribution in the biopsies. Through this unique data analysis pipeline to processing massive LIBS spectroscopic data, it was possible to detect and locate exotic elements such as tin and rhodium in a patient's tissue section, ultimately leading to a possible reclassification of their lung condition as an occupational disease. This review will thus demonstrate the potential of this new diagnostic tool based on LIBS imaging in addressing the shortcomings of approaches developed thus far. The proposed data processing approach naturally transcends this specific framework and can be leveraged across various domains of analytical chemistry, where the detection of rare events is concealed within extensive data sets.

Agricultural activities and risk of Alzheimer's disease: the TRACTOR project, a nationwide retrospective cohort study.

Data regarding Alzheimer's disease (AD) occurrence in farming populations is lacking. This study aimed to investigate whether, among the entire French farm manager (FM) workforce, certain agricultural activities are more strongly associated with AD than others, using nationwide data from the TRACTOR (Tracking and monitoring occupational risks in agriculture) project. Administrative health insurance data (digital electronic health/medical records and insurance claims) for the entire French agricultural workforce, over the period 2002-2016, on the entire mainland France were used to estimate the risk of AD for 26 agricultural activities with Cox proportional hazards model. For each analysis (one for each activity), the exposed group included all FMs that performed the activity of interest (e.g. crop farming), while the reference group included all FMs who did not carry out the activity of interest (e.g. FMs that never farmed crops between 2002 and 2016). There were 5067 cases among 1,036,069 FMs who worked at least one year between 2002 and 2016. Analyses showed higher risks of AD for crop farming (hazard ratio (HR) = 3.72 [3.47-3.98]), viticulture (HR = 1.29 [1.18-1.42]), and fruit arboriculture (HR = 1.36 [1.15-1.62]). By contrast, lower risks of AD were found for several animal farming types, in particular for poultry and rabbit farming (HR = 0.29 [0.20-0.44]), ovine and caprine farming (HR = 0.50 [0.41-0.61]), mixed dairy and cow farming (HR = 0.46 [0.37-0.57]), dairy farming (HR = 0.67 [0.61-0.73]), and pig farming (HR = 0.30 [0.18-0.52]). This study shed some light on the association between a wide range of agricultural activities and AD in the entire French FMs population.

Farming activity and risk of treated thyroid disorders: Insights from the TRACTOR project, a nationwide cohort study.

BACKGROUND: Epidemiological data regarding thyroid diseases are lacking, in particular for occupationally exposed populations. OBJECTIVES: To compare the risk of hypothyroidism and hyperthyroidism between farming activities within the complete population of French farm managers (FMs). METHODS: Digital health data from retrospective administrative databases, including insurance claims and electronic health/medical records, was employed. This cohort data spanned the entirety of French farm managers (FMs) who had undertaken work at least once from 2002 to 2016. Survival analysis with the time to initial medication reimbursement as timescale was used to examine the association (hazard ratio, HR) between 26 specific farming activities and both treated hypothyroidism and hyperthyroidism. A distinct model was developed for each farming activity, comparing FMs who had never engaged in the specific farming activity between 2002 and 2016 with those who had. All analyses were adjusted for potential confounders (e.g., age), and sensitivity analyses were conducted. RESULTS: Among 1088561 FMs (mean age 46.6 [SD 14.1]; 31% females), there were 31834 hypothyroidism cases (75% females) and 620 hyperthyroidism cases (67% females), respectively. The highest risks were observed for cattle activities for both hyperthyroidism (HR ranging from 1.75 to 2.42) and hypothyroidism (HR ranging from 1.41 to 1.44). For hypothyroidism, higher risks were also observed for several animal farming activities (pig, poultry, and rabbit), as well as fruit arboriculture (HR = 1.22 [1.14-1.31]). The lowest risks were observed for activities involving horses. Sex differences in the risk of hypothyroidism were observed for eight activities, with the risk being higher for males (HR = 1.09 [1.01-1.20]) than females in viticulture (HR = 0.97 [0.93-1.00]). The risk of hyperthyroidism was two times higher for male dairy farmers than females. DISCUSSION: Our findings offer a comprehensive overview of thyroid disease risks within the FM community. Thyroid ailments might not stem from a single cause but likely arise from the combined effects of various causal agents and triggering factors (agricultural exposome). Further investigation into distinct farming activities-especially those involving cattle-is essential to pinpoint potential risk factors that could enhance thyroid disease monitoring in agriculture.

Agricultural activities and risk of central nervous system tumors among French farm managers: Results from the TRACTOR project.

The etiology of central nervous system (CNS) tumors is complex and involves many suspected risk factors. Scientific evidence remains insufficient, in particular in the agricultural field. The goal of our study was to investigate associations between agricultural activities and CNS tumors in the entire French farm manager workforce using data from the TRACTOR project. The TRACTOR project hold a large administrative health database covering the entire French agricultural workforce, over the period 2002-2016, on the whole French metropolitan territory. Associations were estimated for 26 activities and CNS tumors using Cox proportional hazards model, with time to first CNS tumor insurance declaration as the underlying timescale, adjusting for sex, age and geographical area. There were 1017 cases among 1 036 069 farm managers, including 317 meningiomas and 479 gliomas. Associations varied with tumor types, sex and types of crop and animal farming. Analyses showed several increased risks of CNS tumors, in particular for animal farming. The main increases in risk were observed for meningioma in mixed dairy and cow farming (hazard ratio [HR] = 1.75, 95% confidence interval [CI]: 1.09-2.81) and glioma in pig farming (HR = 2.28, 95% CI: 1.37-3.80). Our study brings new insights on the association of a wide range of agricultural activities and CNS tumor and subtype-specific risks in farm managers. Although these findings need to be corroborated in further studies and should be interpreted cautiously, they could have implications for enhancing CNS tumor surveillance in agriculture.

Spatio-temporal clustering of amyotrophic lateral sclerosis in France: A population-based study.

OBJECTIVE: To assess spatial aggregates of amyotrophic lateral sclerosis (ALS) incident cases, using a solid geo-epidemiological statistical method, in France. METHODS: This population-based study (2003-2011) investigated 47.1 million person-years of follow-up (PYFU). Case ascertainment of incident ALS cases was based on multiple sources (ALS referral centers, hospital centres and health insurance data). Neurologists confirmed all ALS diagnoses. Exhaustiveness was estimated through capture-recapture. Aggregates were investigated in four steps: (a) geographical modelling (standardized incidence ratio (SIR) calculation), (b) analysis of the spatial distribution of incidence (Phothoff-Winttinghill's test, Global Moran's Index, Kulldorf's spatial scan statistic, Local Moran's Index), (c) classification of the level of certainty of spatial aggregates (i.e. definite cluster; probable over-incidence area; possible over-incidence area) and (d) evaluation of the robustness of the results. RESULTS: The standardized incidence of ALS was 2.46/100,000 PYFU (95% CI 2.31-2.63, European population as reference) based on 1199 incident cases. We identified 13 areas of spatial aggregates: one cluster (stable in robustness analysis), five probable over-incidence areas (2 stable in robustness analysis) and seven possible over-incidence areas (including 4 stable areas in robustness analysis). A cluster was identified in the Rhône-Alpes region: 100 observed vs 54.07 expected cases for 2,411,514 PYFU, SIR: 1.85 (95% CI 1.50-2.25). CONCLUSION: We report here one of the largest investigations of incidence and spatial aggregation of ALS ever performed in a western country. Using a solid methodology framework for case ascertainment and cluster analysis, we identified 13 areas that warrant further investigation.

Characterization of foreign materials in paraffin-embedded pathological specimens using in situ multi-elemental imaging with laser spectroscopy.

Pathologists typically encounter many disparate exogenous materials in clinical specimens during their routine histopathological examinations, especially within the skin, lymph nodes, and lungs. These foreign substances may be free extracellular deposits or induce several clinical abnormalities or histopathological patterns. However, pathologists almost never investigate or report the chemical nature of exogenous metals in clinical specimens due to a lack of convenient and available technologies. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) technology is evaluated for in situ multi-elemental tissue imaging. The improved procedures allow visualization of the presence of chemical elements contained within paraffin-embedded specimens of medical interest with elemental images that are stackable with conventional histology images. We selected relevant medical situations for which the associated pathology reports were limited to the presence of lymphohistiocytic and inflammatory cells containing granules (a granuloma and a pseudolymphoma) or to lymph nodes or skin tissues containing pigments or foreign substances. Exogenous elements such as aluminum, titanium, copper, and tungsten were identified and localized within the tissues. The all-optical LIBS elemental imaging instrument that we developed is fully compatible with conventional optical microscopy used for pathology analysis. When combined with routine histopathological analysis, LIBS is a versatile technology that might help pathologists establish or confirm diagnoses for a wide range of medical applications, particularly when the nature of external agents present in tissues needs to be investigated.

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.

Urinary elimination kinetics of 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene of workers in a prebake aluminum electrode production plant: Evaluation of diuresis correction methods for routine biological monitoring.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous carcinogenic pollutants emitted in complex mixtures in the ambient air and contribute to the incidence of human cancers. Taking into account all absorption routes, biomonitoring is more relevant than atmospheric measurements to health risk assessment, but knowledge about how to use biomarkers is essential. In this work, urinary elimination kinetic of 1-hydroxypyrene (1-OHP) and 3-hydroxybenzo(a)pyrene (3-OHBaP) were studied in six electrometallurgy workers after PAHs exposure. Spot samples were collected on pre- and post-shift of the last workday then the whole urinations were separately sampled during the weekend. Non-linear mixed effects models were built to study inter- and intra-individual variability of both urinary metabolites toxicokinetic and investigate diuresis correction ways. Comparison of models confirmed the diuresis correction requirement to perform urinary biomonitoring of pyrene and BaP exposure. Urinary creatinine was found as a better way than specific gravity to normalize urinary concentrations of 1-OHP and as a good compromise for 3-OHBaP. Maximum observed levels were 1.0 µmol/mol creatinine and 0.8nmol/mol creatinine for 1-OHP and 3-OHBaP, respectively. Urinary 1-OHP concentrations on post-shift were higher than pre-shift for each subject, while 3-OHBaP levels were steady or decreased, and maximum urinary excretion rates of 3-OHBaP was delayed compared to 1-OHP. These results were consistent with the sampling time previously proposed for 3-OHBaP analysis, the next morning after exposure. Apparent urinary half-life of 1-OHP and 3-OHBaP ranged from 12.0h to 18.2h and from 4.8h to 49.5h, respectively. Finally, inter-individual variability of 1-OHP half-life seemed linked with the cutaneous absorption extent during exposure, while calculation of 3-OHBaP half-life required the awareness of individual urinary background level. The toxicokinetic modeling described here is an efficient tool which could be used to describe elimination kinetic and determine diuresis correction way for any other urinary biomarkers of chemicals or metals exposure.

Geographic dimensions of a health network dedicated to occupational and work related diseases.

BACKGROUND: Although introduced nearly 40 years ago, Geographic Information Systems (GISs) have never been used to study Occupational Health information regarding the different types, scale or sources of data. The geographic distribution of occupational diseases and underlying work activities were always analyzed independently. Our aim was to consider the French Network of Occupational Disease (OD) clinics, namely the "French National OD Surveillance and Prevention Network" (rnv3p) as a spatial object in order to describe its catchment. METHODS: We mapped rnv3p observations at the workplace level. We initially analyzed rnv3p capture with reference to its own data, then to the underlying workforce (INSEE "Employment Areas"), and finally compared its capture of one emblematic occupational disease (mesothelioma) to an external dataset provided by a surveillance system thought to be exhaustive (PNSM). RESULTS: While the whole country is covered by the network, the density of observations decreases with increase in the distance from the 31 OD clinics (located within the main French cities). Taking into account the underlying workforce, we show that the probability to capture and investigation of OD (assessed by rates of OD per 10,000 workers) also presents large discrepancies between OD clinics. This capture rate might also show differences according to the disease, as exemplified by mesothelioma. CONCLUSION: The geographic approach to this network, enhanced by the possibilities provided by the GIS tool, allow a better understanding of the coverage of this network at a national level, as well as the visualization of capture rates for all OD clinics. Highlighting geographic and thematic shading zones bring new perspectives to the analysis of occupational health data, and should improve occupational health vigilance and surveillance.

Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012.

OBJECTIVES: The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. METHODS: OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of 'centres', requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. RESULTS: Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. CONCLUSIONS: This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods.

Occupational exposure to polycyclic aromatic hydrocarbons: relations between atmospheric mixtures, urinary metabolites and sampling times.

PURPOSE: Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by either air monitoring or biomonitoring using urinary 1-hydroxypyrene (1-OHP) or 3-hydroxybenzo(a)pyrene (3-OHBaP). The aim of this study was to understand the links between atmospheric PAHs and urinary metabolites, in order to improve the biomonitoring strategy for assessing carcinogenic risk. METHODS: Personal air sampling for pyrene and BaP measurements, and urines for 1-OHP and 3-OHBaP analyses of seven workers from electrode production plant were collected every day of the working week. RESULTS: High variability of atmospheric levels between activities and between days was observed, especially for gaseous pyrene. No correlation was found between urinary metabolites: 1-OHP maximum levels occurred for "electrode extrusion" activity; those of 3-OHBaP occurred for "raw materials dispatcher." Sixty percentage of 3-OHBaP maximum levels were observed in urines collected at the beginning of shift the last workday. Those of 1-OHP occurred at different sampling times, depending on the gaseous pyrene levels (not stopped by P3 respirators). Dermal absorption of PAHs was confirmed by significant effect of particulate pyrene on 1-OHP in the samples collected the morning of the following day (p < 0.02, n = 25). CONCLUSIONS: Lack of correlation between metabolites concentrations emphasizes the non-relevance of 1-OHP, from a non-carcinogenic gaseous and particulate compound, and the great interest of 3-OHBaP, from carcinogenic BaP. Its slower urinary elimination prevents the risk of exposure underestimation, and urinary analysis should be performed at the beginning of shift the end of working week, especially in case of high exposure variability.

LOW-BACK PAIN DISORDERS AS OCCUPATIONAL DISEASES IN THE CZECH REPUBLIC AND 22 EUROPEAN COUNTRIES: COMPARISON OF NATIONAL SYSTEMS, RELATED DIAGNOSES AND EVALUATION CRITERIA.

AIM: Low-back pain diseases (LBPD) belong to the most frequent diagnoses determined by general practitioners, and constitute one of the most common reasons for sick leave and permanent disability pension in the Czech Republic and other European countries. Epidemiological studies have shown a statistically significant association between LBPD and certain types of occupational burden. However, in the Czech Republic, LBPD caused by overload and/or whole-body vibrations have not yet been included in the list of occupational diseases. The aim of this study was to collect and compare the systems, criteria and diagnoses used to recognize LBPD as occupational diseases in other European countries. METHODS: A questionnaire focused on LBPD was distributed and answered by specialists in occupational diseases in European countries. It included items concerning LBPD in the national list of occupational diseases, and work-related and diagnostic criteria that need to be fulfilled for recognizing LBPD as occupational diseases and possible awarding compensations to the patients. RESULTS: In 13 countries out of the 23 countries studied, LBPD caused by overload can be recognized as occupational, providing that the diagnosis is sufficiently proven and exposure criteria and/or listed occupation are met and duration of exposure is confirmed (Belgium, Denmark, France, Germany, Hungary, Italy, Lithuania, Macedonia, Netherlands, Romania, Slovakia, Sweden, and Switzerland). LBPD due to vibrations can be also recognized as occupational in 14 countries. In 8 countries LBPD are not accepted as occupational unless they are caused by an injury at work. Specific criteria to evaluate occupational exposure of patients with LBPD were set in Belgium, Denmark, France, Germany, Lithuania, Macedonia, Netherlands, and Slovakia. In other countries, the evaluation is done at an individual basis. CONCLUSIONS: In practice, the assessment of occupational overload and its contribution to the development of LBPD as well as its inclusion in the compensation system are important for several reasons. Firstly, it may be considered essentially preventable. Secondly, cases with a significant contribution of occupational aetiology may be viewed as occupational diseases for which compensation may be claimed, as it is the case in many European countries. Importantly, inclusion of LBPD in the list of occupational diseases or another system of compensation may be viewed as a preventive measure as it increases the visibility of this problem not only for the workers, but especially for the employers.

Farming activities and risk of inflammatory bowel disease: a French nationwide population-based cohort study.

BACKGROUND AND AIMS: Epidemiological data regarding inflammatory bowel disease (IBD) are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager (FM) workforce, certain agricultural activities are more strongly associated with IBD than others. METHODS: Nationwide population-based insurance claims and electronic health records from all FMs that worked at least once over the period 2002-2016 were used (n=1088561, 69% males). The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC), measured as hazard ratios (HRs), after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying timescale. A model was generated for every activity and disease, utilizing a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016. RESULTS: There were 1752 IBD cases, with 704 CD (40.2%) and 1048 UC (59.8%) cases, respectively. Elevated HRs were observed for fruit arboriculture (HR from 1.17 to 1.52) and dairy farming (HR from 1.22 to 1.46) for all IBD, in crop farming for CD only (HR=1.26 [95CI%: 1.06-1.49]), and in shellfish farming (HR from 2.12 to 2.51) for both CD and IBD. CONCLUSIONS: Further research regarding specific farming activities and exposures likely to modify the microbiota (e.g., pesticides, pathogens) is required to identify potential occupational risk factors (agricultural exposome) for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues.

Occupational asthma and occupational rhinitis: the united airways disease model revisited.

OBJECTIVES: Whereas accumulating evidence indicates close associations between rhinitis and asthma, little is known about the relationships between occupational rhinitis (OR) and occupational asthma (OA). This study analyses the prevalence of OR associated with OA, globally and according to the various causal agents, and investigates the temporal relationships between these two conditions. METHODS: Data on incident cases of OA (2008-2010) were collected through the French national occupational disease surveillance and prevention network, using a standardised form including information on occupation, causal agents, presence of OR, and respective dates of occurrence of rhinitis and asthma. RESULTS: Among the 596 reported OA cases with latency period, 555 could be attributed to identified agents: high molecular weight (HMW) agents (n=174); low molecular weight (LMW) agents (n=381). Overall, OR was associated with OA in 324 (58.4%) cases. The frequency of association was significantly higher for HMW agents than for LMW agents (72.2% vs 51.5%, p<0.001). OR occurred before OA significantly more frequently for HMW agents than for LMW agents (p<0.01). CONCLUSIONS: These results show that OR is frequently associated with OA, especially when HMW agents are involved. They are consistent with the hypothesis that OR, in conjunction with OA, is more likely to be caused by sensitisers that cause disease via IgE-mediated mechanisms and suggest that symptoms of OR should be taken into account in the medical surveillance of workers exposed to HMW agents.

Agricultural activities and risk of treatment for depressive disorders among the entire French agricultural workforce: the TRACTOR project, a nationwide retrospective cohort study.

Background: Although depression is a major issue among farming population, to date, there have been few studies on specific agricultural activities. We aimed to investigate whether, among the entire French farm manager (FM) workforce, certain agricultural activities are more strongly associated with depression than others. Methods: This nationwide retrospective cohort study used data from an administrative health database available to the TRACTOR project. This database pertains to the entire French agricultural workforce (overseas workers not included). Data were analyzed from January 2021 to December 2022. All FMs that worked at least once over the period 2002-2016 were included. The outcome measure was the association between 26 agricultural activities and the risk of depression measured as hazard ratios (HRs) after adjusting for age, sex, and pre-existing medical comorbidities. The time to first depression insurance declaration, or first antidepressant prescription claim was used as the underlying timescale. For each activity, the reference/control group included all FMs that never performed the considered activity between 2002 and 2016, while the exposed group included FMs that performed the considered activity at least once from 2002 to 2016. Four sensitivity analyses were conducted to test hypotheses, and to address potential sources of bias. Findings: There were 84,507 (7.76%; 28.2 cases per 1000 person-years) depression cases among 1,088,561 FMs (mean age 46.6 [SD 14.1]). Compared to other activities, dairy farming (HR = 1.37, 95% confidence interval: 1.32-1.42), cow farming (HR = 1.53 [1.47-1.59]), poultry and rabbit farming (HR = 1.37 [1.27-1.50]), and mixed farming (HR = 1.30 [1.24-1.36]) were more strongly associated with depression. Sex differences were observed, with most of the time, risks higher for females than for males. Interpretation: Agricultural activities at risk of depression among the entire French agricultural workforce were identified. These findings do represent a crucial first step on the road to implement effective preventive measures against depression to determine where additional resources should be allocated to screen for depression, along with intervention. Funding: MIAI@Grenoble Alpes, and Mutualité Sociale Agricole.

Does prenatal exposure to multiple airborne and tap-water pollutants increase neonatal thyroid-stimulating hormone concentrations? Data from the Picardy region, France.

OBJECTIVE: Systematic screening for congenital hypothyroidism by heel-stick sampling has revealed unexpected heterogeneity in the geographic distribution of newborn thyroid-stimulating hormone concentrations in Picardy, France. We explored a possible relationship with environmental pollutants. METHODS: Zip code geolocation data from mothers of newborns without congenital hypothyroidism born in 2021 were linked to ecological data for a set of airborne (particulate matter with a diameter of 2.5 µm or less [PM2.5] or 10 µm or less [PM10]) and tap-water (nitrate and perchlorate ions and atrazine) pollutants. Statistical associations between mean exposure levels during the third trimester of pregnancy and Thyroid-stimulating hormone (TSH) concentrations in 6249 newborns (51 % male) were investigated using linear regression models. RESULTS: Median neonatal TSH concentration (interquartile range, IQR) was 1.7 (1-2.8) mIU/L. An increase of one IQR in prenatal exposure to perchlorate ions (3.6 µg/L), nitrate ions (19.2 mg/L), PM2.5 (3.7 µg/m3) and PM10 (3.4 µg/m3), were associated with increases in TSH concentrations of 2.30 % (95 % CI: 0.95-3.66), 5.84 % (95 % CI: 2.81-8.87), 13.44 % (95 % CI: 9.65-17.28) and 6.26 % (95 % CI: 3.01-9.56), respectively. CONCLUSIONS: Prenatal exposure to perchlorate and nitrate ions in tap water and to airborne PM over the third trimester of pregnancy was significantly associated with increased neonatal TSH concentrations.

Work-related asthma in France: recent trends for the period 2001-2009.

OBJECTIVE: Knowledge on the time-course (trends) of work-related asthma (WRA) remains sparse. The aim of this study was to describe WRA trends in terms of industrial activities and the main causal agents in France over the period 2001-2009. METHOD: Data were collected from the French national network of occupational health surveillance and prevention (Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)). Several statistical models (non-parametric test, zero-inflated negative binomial, logistic regression and time-series models) were used and compared with assess trends. RESULTS: Over the study period, 2914 WRA cases were included in the network. A significant decrease was observed overall and for some agents such as isocyanates (p = 0.007), aldehydes (p = 0.01) and latex (p = 0.01). Conversely, a significant increase was observed for cases related to exposure to quaternary ammonium compounds (p = 0.003). The health and social sector demonstrated both a growing number of cases related to the use of quaternary ammonium compounds and a decrease of cases related to aldehyde and latex exposure. CONCLUSIONS: WRA declined in France over the study period. The only significant increase concerned WRA related to exposure to quaternary ammonium compounds. Zero-inflated negative binomial and logistic regression models appear to describe adequately these data.

Cancer incidence in a chlorochemical plant in Isère, France: an occupational cohort study, 1979-2002.

BACKGROUND: A major French chlorine chemical plant (chlor-alkali process with diaphragm cell and manufacturing of organochlorine chemicals) has used or produced known or suspected carcinogenic compounds. METHODS: A cohort study, based on the plant occupational health service and the regional cancer registry, analyzed the standardized incidence ratios of malignant tumors for the period 1979-2002. Individual exposures were estimated from workers' occupational histories in a dual division of jobs into 9 sectors and 115 workshops with known exposures. RESULTS: Men (2,742) were followed, corresponding to 52,794 person-years. Primary tumors (304) were observed for 290 expected cases, a non-significant 5% excess. A significant excess was found of pleural mesothelioma and bladder cancer in employees hired before 1964. CONCLUSION: Excesses of mesothelioma and bladder cancer were found, whereas there was no excess of hematopoietic cancers despite high benzene and dioxin exposures. Surprisingly, mesothelioma cases did not include workers who were the most exposed to asbestos.