Ischemic stroke subtypes: risk factors, treatments, and 1-month prognosis - The Lille, France Stroke Registry.

OBJECTIVES: First, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes' etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality. MATERIALS AND METHODS: All ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model. RESULTS: 1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription. CONCLUSIONS: While atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke.

Association between residential air pollution exposure and cardiovascular risk factors in adults living in northern France.

Air pollution is associated with elevated cardiovascular mortality and an increase in cardiovascular risk factors. However, the literature data on associations between air pollution and cardiovascular risk factors are contradictory. To explore the relationship between residential exposure to atmospheric pollutants and cardiovascular risk factors (lipid biomarker and blood pressure levels). We studied a sample of 2339 adult participants in the ELISABET study from the Dunkirk and Lille urban areas of France. The mean annual exposure to atmospheric pollutants (PM10, NO2 and SO2) at the home address was estimated via an air dispersion model. The associations were probed in multivariate linear regression models. The mean NO2 level was 26.05 µg/m3 in Lille and 19.96 µg/m3 in Dunkirk. The mean PM10 level was 27.02 µg/m3 in Lille and 26.53 µg/m3 in Dunkirk. We detected a significant association between exposure to air pollutants and the high-density lipoprotein (HDL) (which is a protective factor against cardiovascular diseases) level: for a 2 µg/m3 increment in PM10, the HDL level decreased by 1.72% (p = 0.0037). None of the associations with other lipid variables or with blood pressure were significant. We didn't find evidence significant associations for most of the risk factors but, long-term exposure of adults to moderate levels of ambient air pollution was associated with a decrement in HDL.

The impact of occupational exposure to crystalline silica dust on respiratory function (airway obstruction and FEF25-75) in the French general population.

INTRODUCTION: Although several studies have studied the relationship between occupational exposure to crystalline silica dust and respiratory mortality, few have examined the relationship with impairments in respiratory function and the exposure threshold triggering spirometric monitoring in exposed workers. The objective of the present study was to evaluate the impact of exposure to crystalline silica dust on respiratory function. METHODS: We included 1428 male participants (aged 40 to 65) recruited from the French general population, at random from electoral rolls, in the cross-sectional ELISABET study and for whom data on forced expiratory flow-volume curve indices z-scores (calculated using the Global Lung Function Initiative 2012 equations) and exposure (via a questionnaire) were available. A cumulative exposure index (CEI) for crystalline silica dust (CEIsilica, expressed in mg.m-3.year) was calculated using the Matgéné occupational exposure matrix. RESULTS: 293 of the 1428 participants (20.52%) reported exposure to silica dust. We found that the adjusted z-scores for the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio decreased significantly as CEIsilica increased. After adjustment, the adjusted z-scores for FEV1/FVC (ß: -0.426 (95% confidence interval (CI): -0.792, -0.060) per 1 mg m-3.year increment) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) (ß: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEIsilica ≥1 mg m-3.year than in non-exposed participants. The likelihoods of having airway obstruction (odds ratio (OR): 3.056 (95% CI: 1.107, 7.626)) or having an impaired FEF25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEIsilica ≥1 mg m-3.year. CONCLUSION: Our results emphasize the importance of spirometry-based monitoring in workers exposed to more than 1 mg m-3.year of crystalline silica dust, in order to identify small airway obstruction or airway obstruction as early as possible.

Residential exposure to outdoor air pollution and adult lung function, with focus on small airway obstruction.

Although a growing body of evidence suggests that chronic exposure to outdoor air pollution is linked to a decline in lung function, data on flow at low lung volumes that may be more specific of small airway obstruction are still scarce. We aimed to study the associations between residential exposure to air pollution and lung function, with specific focus on small airways obstruction. We assessed 2995 French participants (aged between 40 and 65) in the ELISABET cross-sectional survey. Residential exposures to nitrogen dioxide (NO2), particulate matter with a diameter <10 µm (PM10) and sulphur dioxide (SO2) were assessed. The spirometric parameters were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) and at 75% of FVC (FEF75). Coefficients in linear regression models were expressed as the z-score [95% confidence interval] for an increment of 5 µg/m3 in NO2 and 2 µg/m3 in PM10 and SO2. NO2 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.05]), FVC (-0.06 [-0.11;-0.02]), FEV1/FVC (-0.07 [-0.11;-0.03]), FEF25-75 (-0.09 [-0.14;-0.05]) and FEF75 (-0.08 [-0.12;-0.04]). PM10 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.04]), FVC (-0.06 [-0.11;-0.01]), FEV1/FVC (-0.06 [‒0.11;-0.01]), FEF25-75 (-0.08 [-0.13;-0.03]) and FEF75 (-0.08 [-0.12;-0.04]). SO2 was associated with significantly lower values of FEV1 (-0.09 [-0.16;-0.02]), FEV1/FVC (-0.07 [-0.13;-0.01]), FEF25-75 (-0.09 [-0.15;-0.02]) and FEF75 (-0.08 [-0.14;-0.03]) but not FVC (-0.05 [-0.11; 0.009]). Even though spatial variations in pollutant levels were low, residential exposure to outdoor air pollution was associated with lower lung function, including lower FEF25-75 and FEF75 suggesting small airway obstruction.

The association between blood cadmium and glycated haemoglobin among never-, former, and current smokers: A cross-sectional study in France.

INTRODUCTION: The association between cadmium levels in the body and diabetes has been extensively studied, with sometimes contrasting results. Smoking is the primary non-occupational source of cadmium, and constitutes a risk factor for diabetes. One can therefore hypothesize that the putative association with cadmium is actually explained by tobacco. To fully control for this confounding factor, we studied the relationship between blood cadmium and glycated haemoglobin (HbA1c) levels separately in never-, former and current smokers. METHODS: We studied a sample of 2749 middle-aged adults from the cross-sectional ELISABET survey in and around the cities of Lille and Dunkirk; none had chronic kidney disease or a history of haematological disorders, and none were taking antidiabetic medication. The blood cadmium level-HbA1c associations in never-, former and current smokers were studied in separate multivariate models. The covariables included age, sex, city, educational level, tobacco consumption (or passive smoking, for the never-smokers), body mass index, estimated glomerular filtration rate, and (to take account of the within-batch effect) the cadmium batch number. RESULTS: In the multivariate analysis, a significant association between cadmium and HbA1c levels was found in all three smoking status subgroups. A 0.1 µg/L increment in blood cadmium was associated with an HbA1c increase [95% confidence interval] of 0.016% [0.003; 0.029] among never-smokers, 0.024% [0.010; 0.037] among former smokers, and 0.020% [0.012; 0.029] among current smokers. CONCLUSIONS: The observation of a significant association between the blood cadmium concentration and HbA1c levels in a group of never-smokers strengthens the hypothesis whereby diabetes is associated with cadmium per se and not solely with tobacco use. The small effect size observed in our population of never smokers with low levels of exposure to cadmium suggested that the risk attributable to this metal is not high. However, the impact of exposure to high cadmium levels (such as occupational exposure) on the risk of diabetes might be of concern.

Sources of household air pollution: The association with lung function and respiratory symptoms in middle-aged adult.

INTRODUCTION: The objective of the present study was to investigate the relationship between sources of household air pollution, respiratory symptoms and lung function. METHODS: 3039 adults aged from 40 to 65 participated in the 2011-2013 ELISABET cross-sectional survey in northern France. Lung function was measured using spirometry. During a structured interview, respiratory symptoms, household fuels, exposure to moulds, and use of ventilation were recorded on a questionnaire. RESULTS: The self-reported presence of mould in at least two rooms (not including the bathroom and the kitchen) was associated with a 2.5% lower predicted forced expiratory volume in 1 s (95% confidence interval, -4.7 to -0.29; p-trend <0.05) and a higher risk of wheezing (p-trend < 0.001). Visible condensation was associated with wheezing (p < .05) and chronic cough (p < .05). There were no significant associations with the type of household fuel or inadequate ventilation/aeration. Similar results were found when the analyses were restricted to participants without known respiratory disease. CONCLUSION: Our results suggest that the presence of mould (known to be associated with more severe asthma symptoms) could also have an impact on respiratory symptoms and lung function in the general population and in populations without known respiratory disease.

Cancer in Elderly Onset Inflammatory Bowel Disease: A Population-Based Study.

OBJECTIVES: Cancer may be a complication of inflammatory bowel disease (IBD) or its treatment. In elderly onset IBD patients the risk of malignancy is of particular concern. We studied this risk in a population-based cohort of elderly onset IBD patients. METHODS: In a French population-based cohort, we identified 844 patients aged >60 years at IBD diagnosis from 1988 to 2006, including 370 Crohn's disease (CD) and 474 ulcerative colitis (UC). We compared incidence of cancer among IBD patients with that observed in the French Network of population-based Cancer Registries (FRANCIM). Confidence interval (CI) was estimated assuming a Poisson-specific law for rare events. Results were expressed using the standardized incidence ratios (SIRs) and their CI 95%. RESULTS: Median age at IBD diagnosis was 70 (65-76) years in CD and 69 (64-74) in UC. Median follow-up was 6 (2-11) years for both diseases with a number of person-years of 5,598. Among the 844 elderly onset IBD cases, 98 (11.6%; 42 CD and 56 UC) developed a cancer after IBD diagnosis (67 men and 31 women) corresponding to an overall SIR of 0.97 (0.80-1.18). These cancers occurred at a median age of 77 years (71-80) and 75 years (71-81) in patients with CD and UC, respectively. Median time between IBD diagnosis and cancers was 78 months (40-121). There was no significant increased risk of colorectal cancer in IBD (SIR=1.03 (0.62-1.70), CD (SIR=1.20 (0.57-2.52) nor in UC (SIR=0.91 (0.45-1.82) without significant protective role of 5-aminosalicylic acid (hazard ratio (HR)=0.7 (0.2-2.6)). No significant risk for other intestinal cancers was found, especially for small bowel carcinoma. An increased risk of malignant lymphoproliferative disorders was found in all IBD and in CD: SIR=2.49 (1.25-4.99) and SIR=3.09 (1.16-8.23), respectively. An increased risk of myeloproliferative disorders was found in all IBD (SIR=2.18 (1.09-4.35)). Thiopurines exposure, using a time-dependant Cox model, was not found as associated with an increased risk to develop cancer, HR=0.90 (0.48-1.68). CONCLUSIONS: There is no increased risk for developing intestinal cancer among patients with elderly onset IBD in this population-based cohort. There are increased risks of developing lymphoproliferative and myeloproliferative disorders in all IBD. Thiopurines exposure was not found as associated with an increased risk to lymphoproliferative disorders. These data reinforce the difference between elderly onset IBD as compared with patients with younger age at IBD onset.

Vaccination and Risk for Developing Inflammatory Bowel Disease: A Meta-Analysis of Case-Control and Cohort Studies.

BACKGROUND & AIMS: Environmental factors may play a key role in the pathogenesis of inflammatory bowel disease (IBD). Whether vaccination is associated causally with IBD is controversial. We performed a meta-analysis of case-control and cohort studies on the association between vaccination and the risk for IBD. METHODS: Studies and abstracts investigating the relationship between vaccination and subsequent risk for developing IBD were reviewed. Childhood or adult immunizations with any vaccine type, at any dose, and with any vaccine schedule were used as inclusion criteria. RESULTS: Eleven studies were included in the systematic review and meta-analysis: 8 case-control studies and 3 cohort studies. Studied vaccines were bacille Calmette-Guérin), vaccines against diphtheria, tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and the combined measles, mumps, and rubella vaccine. Only a few details about vaccine type or route of administration were found in studies. Overall, there was no association between childhood immunization and risk for developing IBD: bacille Calmette-Guérin, relative risk (RR) of 1.04 (95% confidence interval [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27 (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI, 0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC) found an association between the poliomyelitis vaccine and risk for developing CD (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32). CONCLUSIONS: Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD. The association between the poliomyelitis vaccine and the risk for CD or UC should be analyzed with caution because of study heterogeneity.

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.

UNLABELLED: Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. METHODS: In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC). RESULTS: Median age at diagnosis was similar for CD (70 years (IQR: 65-76)) and UC (69 years (64-74)). Median follow-up was 6 years (2-11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. CONCLUSIONS: Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis.

OBJECTIVE: Pulmonary hypertension (PH) is a frequent and life-limiting complication of systemic sclerosis (SSc). However, data on survival rates and their evolution over time, as well as prognostic factors in SSc complicated by PH, are still conflicting. The aim of this study was to conduct a systematic review and meta-analysis of cohort studies to assess pooled survival and prognostic factors for survival in patients with SSc-associated PH. METHODS: For this systematic review and meta-analysis, we searched the Medline and EMBase databases (January 1960 to January 2012). All cohort studies in which survival and/or prognostic factors for SSc-associated PH were reported were included in the analysis. We calculated the pooled survival rates and analyzed their evolution over time and identified prognostic factors for survival. RESULTS: Twenty-two studies were included, representing a total of 2,244 patients with SSc-associated PH. The pooled 1-, 2-, and 3-year survival rates were 81% (95% confidence interval [95% CI] 79-84%), 64% (95% CI 59-69%), and 52% (95% CI 47-58%), respectively. Meta-regression did not reveal a significant change in survival over time, while baseline hemodynamic measures of PH severity were significantly correlated with survival. In patients with SSc complicated by pulmonary arterial hypertension (PAH), age, male sex, diffusing capacity for carbon monoxide (DLCO), pericardial effusion, and the parameters classically associated with the severity of idiopathic PAH, including the 6-minute walk distance, mean pulmonary artery pressure, cardiac index, and right atrial pressure, were significant prognostic factors. DLCO and pericardial effusion were the only prognostic factors in patients with interstitial lung disease-related PH. CONCLUSION: Our meta-analysis revealed a poor pooled 3-year survival rate of 52% in patients with SSc-associated PH. Baseline hemodynamic measures of PAH severity, but not the period of time during which patients were included in the studies, correlated significantly with survival in patients with SSc-associated PAH. All of the prognostic factors typically observed in idiopathic PAH, including the 6-minute walk distance and right atrial pressure, were also prognostic factors in SSc-associated PAH.

[Epidemiology, risk factors and factors associated with disabling course in inflammatory bowel disease]. / Epidémiologie, facteurs de risque et facteurs aggravants des maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases (IBD) are not rare and would affect near of 5 million of patients in the world (including 2.5 in North America and 2.5 in Europe with at least 200,000 in France). These are chronic relapsing disorders affecting young patients (peak of incidence in patients aged from 20 to 30 years), particularly the young females (sex ratio F/M: 1.3). Their cause is unknown and there is no curative treatment. Although many research studies have isolated more than 160 genes whose variants are associated with these diseases, the weight of genetics remains low in their occurrence. Significant time and space variations in incidence of IBD have been reported. Firstly, an increase of IBD incidence has been reported overtime worldwide. Secondly, a space variation in IBD incidence has been noted with a dramatic increase in emerging countries. Even within a same geographical area through a prospective population-based dataset since 27 years (EPIMAD Registry), a spatial heterogeneity of incidence has been reported, suggesting the important role of the environment in the occurrence of these diseases. Smoking and appendectomy are the only environmental factors clearly involved in the development and progression of IBD and cannot explain spatial and temporal heterogeneity in the IBD observed incidence worldwide. New multidisciplinary basic and epidemiological studies are needed to identify the factors involved in the onset of IBD.

The French Experience with a Population-Based Esophageal Atresia Registry (RENATO).

This paper presented a national register for esophageal atresia (EA) started in January 2008. We report our experience about the conception of this database and its coordination. Data management and data quality are also detailed. In 2023, more than 2,500 patients with EA are included. Prevalence of EA in France was calculated at 1.8/10,000 live birth. Main clinical results are listed with scientific publications issued directly from the register.

Air pollution and kidney cancer risk: a systematic review and meta-analysis.

BACKGROUND: Although several risk factors of kidney cancer have already been well-addressed, many remain underappreciated, such as chronic exposure to air pollution. This systematic review and meta-analysis aims to assess the association between air pollutant exposure and the risk of kidney cancer. METHODS: With an exhaustive search equation including keywords related to air pollution and kidney cancer on EMBASE, PubMed, Web of science, Cochrane Library and CINAHL database, we identified all relevant articles published before March 23rd, 2023 (Prospero registration number: CRD42020187956). Using random-effects meta-analysis, we present pooled hazard ratios (with their respective 95% confidence interval) associated with a 10 µg/m3 increase in each pollutant level. Heterogeneity was quantified by the I2 statistic. Risks of methodological and publication bias were also both assessed using appropriate tools. RESULTS: Of the 1919 records identified, our review included 19 articles (13 cohort, 5 registry-based and 1 case-control studies), of which 9 were suitable for the meta-analysis. We found a significantly increased risk of kidney cancer incidence for a 10 µg/m3 elevation of both particulate matter of less than 10 µm (PM10) (HR = 1.29 [1.10; 1.51], I2 = 0%, p = 0.002) and nitrogen dioxide (NO2) (HR = 1.10 [1.03; 1.18], I2 = 20%, p = 0.004). Secondary analyses also suggest an increased risk of kidney cancer-related morbidity-mortality associated with PM10 exposure. CONCLUSIONS: Overall, our findings suggest a potential association between exposure to increased levels of PM10 and NO2 and the risk of kidney cancer. These results should nonetheless be interpreted with caution due to the limited number of included studies and their significant risk of methodological bias.

Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.

OBJECTIVES: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort. METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719). FINDINGS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]). INTERPRETATION: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.

Occupational exposure to crystalline silica in a sample of the French general population.

OBJECTIVE: To describe the proportions of subjects exposed to crystalline silica and the sectors of activity concerned between 1965 and 2010 in a sample of the general French population. METHODS: We included 2942 participants aged 40 to 65 years, recruited at random from electoral rolls, from the French general population in the cross-sectional ELISABET study between 2011 and 2013. The proportions of subjects exposed to crystalline silica and their sectors of activity were determined on the basis of their career history and the use of the Matgéné job-exposure matrix. RESULTS: In the total sample, occupational exposure to crystalline silica was found for 291 subjects (9.9%) between 1965 and 2010, with a predominance of men (20.2% of exposed subjects among men (282 out of 1394) versus 0.6% among women (9 out of 1548)). The highest proportion of participants exposed to crystalline silica was reached in 1980 with 6.1% and then decreases to 4.4% in 2010. Among men, the most frequently exposed sectors of activity were manufacture of basic metals (41.5% of exposed men (117 out of 282)), specialised construction activities (23.1% of exposed men (65 out of 282)) and construction of buildings (14.2% of exposed men (40 out of 282)). CONCLUSIONS: Although the proportion of workers exposed to crystalline silica has been decreasing since the 1980s, it is still significant at least until 2010, particularly in the construction sector, and further research is needed to improve the monitoring of workers who are or have been exposed to crystalline silica.

Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study.

OBJECTIVES: Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. METHODS: All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. RESULTS: A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). CONCLUSIONS: In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

The relationship between residential exposure to atmospheric pollution and circulating miRNA in adults living in an urban area in northern France.

INTRODUCTION: MicroRNAs are epigenetic regulatory factors capable of silencing the expression of target genes and might mediate the effects of air pollution on health. The objective of the present population-based study was to investigate the association between microRNA expression and long-term, residential exposure to atmospheric PM10 and NO2. METHOD: We included 998 non-smoking adult participants from the cross-sectional ELISABET survey (2010-2014) in the Lille urban area of France. The mean residential annual pollution levels were estimated with an atmospheric dispersion modelling system. Ten microRNAs were selected on the basis of the literature data, together with two housekeeping microRNAs (miR-93-5p and miR-191-5p) and were quantified with RT-qPCRs. Multivariate linear regression models were used to study the association between microRNAs and air pollution. The threshold for statistical significance (after correction for the FDR) was set to p < 0.1. RESULTS: The mean annual exposure between 2011 and the year of inclusion was 26.4 ± 2.0 µg/m3 for PM10 and 24.7 ± 5.1 µg/m3 for NO2. Each 2 µg/m3 increment in PM10 exposure was associated with an 8.6% increment (95%CI [3.1; 14.3]; pFDR = 0.019) in miR-451a expression. A 5 µg/m3 increment in NO2 exposure was associated with a 5.3% increment ([0.7; 10]; pFDR = 0.056) in miR451a expression, a 3.6% decrement (95%CI [-6.1; -1.1]; pFDR = 0.052) in miR-223-3p expression, a 3.8% decrement (95%CI[-6.8; -0.7]; pFDR = 0.079) in miR-28-3p expression, a 4.3% decrement (95%CI [-7.7; -0.8]; pFDR = 0.055) in miR-146a-5p expression, and a 4.0% decrement (95% CI[-7.4; -0.4]; pFDR = 0.059) in miR-23a-5p expression. The difference between the two housekeeping microRNAs miR-93-5p and miR-191-5p was also associated with PM10 and NO2 exposure. CONCLUSION: Our results suggest that circulating miRNAs are potentially valuable biomarkers of the effects of air pollution.

Short-term and residential exposure to air pollution: Associations with inflammatory biomarker levels in adults living in northern France.

INTRODUCTION: Air pollution has an impact on health, and low-grade inflammation might be one of the underlying mechanisms. The objective of the present study of adults from northern France was to assess the associations between short-term and residential exposure to air pollution and levels of various inflammatory biomarkers. METHODS: The cross-sectional Enquête Littoral Souffle Air Biologie Environnement (ELISABET) study was conducted from 2011 to 2013 in the Lille and Dunkirk urban areas of northern France. Here, we evaluated the associations between PM10, NO2 and O3 exposure (on the day of the blood sample collection and on the day before, and the mean annual residential level) and levels of the inflammatory biomarkers high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, IL-22, and tumor necrosis factor α. RESULTS: We assessed 3074 participants for the association with hsCRP and a subsample of 982 non-smokers from Lille for the association with plasma cytokine levels. A 10 µg/m3 increment in PM10 and NO2 levels on the day of sample collection and on the day before was associated with a higher hsCRP concentration (3.43% [0.68; 6.25] and 1.75% [-1.96; 5.61], respectively, whereas a 10 µg/m3 increment in O3 was associated with lower hsCRP concentration (-1.2% [-3.95; 1.64]). The associations between mean annual exposure and the hsCRP level were not significant. Likewise, the associations between exposure and plasma cytokine levels were not statistically significant. CONCLUSION: Short-term exposure to air pollution was associated with higher serum hsCRP levels in adult residents of two urban areas in northern France. Our results suggest that along with other factors, low-grade inflammation might explain the harmful effects of air pollution on health.

Effects of occupational and educational changes on obesity trends in France: the results of the MONICA-France survey 1986-2006.

OBJECTIVE: In the past decade, the obesity prevalence in France steadily increased. In the meantime the occupational and educational status of the population improved. This study examined the impact of these changes on obesity trends in France. METHODS: In the MONICA-France surveys in 1986, 1996 and 2006, 5423 men and 5271 women (35-64 yr old) were randomly recruited from electoral rolls in three areas of France (northern, eastern and south-western). We used a logistic regression to assess the association between obesity and time and occupational/educational categories and their interactions and a counterfactual analysis to assess the contributions of occupational and educational changes to obesity trends. RESULTS: Between 1986 and 2006, the prevalence of obesity rose from 15.0% to 18.4% (p < 0.004) in men and remained stable between 15.9% and 17.2% (p = 0.72) in women. Obesity increased in all occupational categories only in men (men: p = 0.0005; women: p < 0.22) and all educational categories in both genders (p < 0.0001). The estimated contributions of occupational (educational) changes to obesity trends were -0.3% (-2.8%) in men and -1.9% (-4.6%) in women. CONCLUSION: The improvement in the French population's occupational status and educational level between 1986 and 2006 tended to reduce the impact of secular trends on the obesity prevalence.