Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort.

OBJECTIVES: The impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Cross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012-2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index. RESULTS: In women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score. CONCLUSIONS: Lifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

Impact of asthma on working life: an analysis of the French CONSTANCES cohort.

OBJECTIVES: Asthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset. METHODS: Using cross-sectional data collected at inclusion in the French CONSTANCES cohort in 2013-2014, we studied the links between each career path indicator (number of job periods, total duration of employment, numbers of part-time jobs and work interruptions due to unemployment or health issues, employment status at inclusion) on the one hand, and current asthma and asthma symptom score in the last 12 months on the other hand, as reported by the participants. Multivariate analyses were performed separately for men and women using logistic and negative binomial regression models adjusted for age, smoking status, body mass index and educational level. RESULTS: When the asthma symptom score was used, significant associations were observed with all of the career path indicators studied: a high symptom score was associated with a shorter total duration of employment as well as a greater number of job periods, part-time jobs and work interruptions due to unemployment or health issues. These associations were of similar magnitude in men and women. When current asthma was used, the associations were more pronounced in women for some career path indicators. CONCLUSION: The career path of asthmatic adults is more often unfavourable than that of those without asthma. Efforts should be made to support people with asthma in the workplace, in order to maintain employment and facilitate the return to work.

Underdiagnosis of obstructive lung disease: findings from the French CONSTANCES cohort.

BACKGROUND: The burden of undiagnosed obstructive lung disease (OLD) (mainly asthma and chronic obstructive pulmonary disease) is not fully established, and targets for corrective action are yet to be identified. We assessed the underdiagnosis of OLD and its determinants in France. METHODS: CONSTANCES is a French population-based cohort of adults aged 18-69 years at inception. We analysed data collected at inclusion in 2013-2014. Undiagnosed OLD was defined as spirometry-confirmed airflow limitation (FEV1/FVC < lower limit of normal) without prior diagnosis of asthma, chronic obstructive pulmonary disease, or bronchiectasis. Multivariate analysis was performed with weighted robust Poisson regression models to estimate the adjusted prevalence ratios (aPR) of undiagnosed OLD. RESULTS: Spirometry results were available for 19,398 participants. The prevalence of airflow limitation was 4.6%. Overall, 64.4% of adults with airflow limitation did not report a previous diagnosis of OLD. Individuals with high cumulative tobacco consumption (≥ 10 pack-years) (aPR: 1.72 [1.28-2.32]), without respiratory symptoms (aPR: 1.51 [1.28-1.78]), and with preserved lung function (aPR: 1.21 [1.04-1.41] for a 10-point increase in FEV1% predicted) had a higher risk of being undiagnosed. Half of symptomatic individuals with airflow limitation (45% of those with moderate to severe airflow limitation) were undiagnosed with OLD. CONCLUSION: Underdiagnosis of OLD is very common among French adults, even in patients with respiratory symptoms. Efforts should be made in France to raise awareness about OLD in the general population, improve the detection of respiratory symptoms, and increase the use of spirometry among primary care professionals.

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

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

An extensive epidemiological investigation of a kidney cancer cluster in a chemical plant: what have we learned?

OBJECTIVES: In 2003, a cluster of renal cell carcinoma (RCC) cases was reported among men working at a French chemical plant using a proprietary process to produce vitamin A. The 10 index cases yielded a standardised incidence ratio of 13.1 for 1994-2002. Nine of these 10 cases were diagnosed by a plant-specific abdominal ultrasonography screening programme that targeted exposure to an intermediate chemical, 4-chloro-1,1-dimethoxy-3-methyl-2-butene, commonly named 'chloracetal C5', suspected as the cause by some experts. Epidemiological investigations sought to examine the relations between occupational exposures and RCC. METHODS: A retrospective cohort mortality study and a nested case--control study were conducted. The cohort study included all workers who had been employed at the plant for at least 6 months between 1960 and 2003. The case--control study included an extensive search within the region for other kidney cancer cases among the cohort members. Industrial hygienists assessed occupational exposure. RESULTS: From 1968 to 2006, no significant excess mortality was observed for all causes of death or for all cancers. We found excess mortality for kidney cancer only among women. The nested case--control study showed a dose--response relation for cumulative exposure to chloracetal C5: the OR rose from 2.5 in the low-exposure category to 10.5 in the high-exposure group. Adjustment for screening attenuated this relation. CONCLUSIONS: The results of the case--control study were consistent with the positive results of in vivo genotoxic tests and suggest that chloracetal C5 can have a causal role in RCC.

Occupational Exposures to Organic Solvents and Asthma Symptoms in the CONSTANCES Cohort.

Solvents are used in many workplaces and may be airway irritants but few studies have examined their association with asthma. We studied this question in CONSTANCES (cohort of 'CONSulTANts des Centres d'Examens de Santé'), a large French cohort. Current asthma and asthma symptom scores were defined by participant-reported respiratory symptoms, asthma medication or attacks, and the sum of 5 symptoms, in the past 12 months, respectively. Lifetime exposures to 5 organic solvents, paints and inks were assessed by questionnaire and a population-based Job-Exposure Matrix (JEM). Cross-sectional associations between exposures and outcomes were evaluated by gender using logistic and negative binomial regressions adjusted for age, smoking habits and body mass index. Analyses included 115,757 adults (54% women, mean age 47 years, 9% current asthma). Self-reported exposure to ≥1 solvent was significantly associated with current asthma in men and women, whereas using the JEM, a significant association was observed only in women. Significant associations between exposures to ≥1 solvent and asthma symptom score were observed for both self-report (mean score ratio, 95%CI, women: 1.36, 1.31-1.42; men: 1.34, 1.30-1.40) and JEM (women: 1.10, 1.07-1.15; men: 1.14, 1.09-1.18). Exposure to specific solvents was significantly associated with higher asthma symptom score. Occupational exposure to solvents should be systematically sought when caring for asthma.

Occupational exposure to polycyclic aromatic hydrocarbons influenced neither the frequency nor the spectrum of FGFR3 mutations in bladder urothelial carcinoma.

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) is associated with an increased risk of urothelial carcinoma (UC). FGFR3 is found mutated in about 70% of Ta tumors, which represent the major group at diagnosis. The influence of PAH on FGFR3 mutations and whether it is related to the emergence or shaping of these mutations is not yet known. We investigated the influence of occupational PAH on the frequency and spectrum of FGFR3 mutations. We included on 170 primary urothelial tumors from five hospitals from France. Patients (median age, 64 yr) were interviewed to gather data on occupational exposure to PAH, revealing 104 non- and possibly PAH exposed patients, 66 probably and definitely exposed patients. Tumors were classified as follows: 75 pTa, 52 pT1, and 43 > or =pT2. Tumor grades were as follows: 6 low malignant potential neoplasms (LMPN) and 41 low-grade and 123 high-grade carcinomas. The SnaPshot method was used to screen for the following FGFR3 mutations: R248C, S249C, G372C, Y375C, A393E, K652E, K652Q, K652M, and K652T. Occupational PAH exposure was not associated with a particular stage or grade of tumors. Thirty-nine percent of the tumors harbored FGFR3 mutations. After adjustment for smoking, occupational exposure to PAH did not influence the frequency [OR, 1.10; 95% CI, 0.78-1.52], or spectrum of FGFR3 mutations. Occupational exposure to PAH influenced neither the frequency nor the spectrum of FGFR3 mutations and there was no direct relationship between these mutations and this occupational hazard.

Attributable risk in men in two French case-control studies on mesothelioma and asbestos.

Pleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR(p)) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR(p) men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR(p) difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR(p) could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR(p) values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection.

Qualitative and Semiquantitative Assessment of Exposure to Engineered Nanomaterials within the French EpiNano Program: Inter- and Intramethod Reliability Study.

The relatively recent development of industries working with nanomaterials has created challenges for exposure assessment. In this article, we propose a relatively simple approach to assessing nanomaterial exposures for the purposes of epidemiological studies of workers in these industries. This method consists of an onsite industrial hygiene visit of facilities carried out individually and a description of workstations where nano-objects and their agglomerates and aggregates (NOAA) are present using a standardized tool, the Onsite technical logbook. To assess its reliability, we implemented this approach for assessing exposure to NOAA in workplaces at seven workstations which synthesize and functionalize carbon nanotubes. The prediction of exposure to NOAA using this method exhibited substantial agreement with that of the reference method, the latter being based on an onsite group visit, an expert's report and exposure measurements (Cohen kappa = 0.70, sensitivity = 0.88, specificity = 0.92). Intramethod comparison of results for exposure prediction showed moderate agreement between the three evaluators (two program team evaluators and one external evaluator) (weighted Fleiss kappa = 0.60, P = 0.003). Interevaluator reliability of the semiquantitative exposure characterization results was excellent between the two evaluators from the program team (Spearman rho = 0.93, P = 0.03) and fair when these two evaluators' results were compared with the external evaluator's results. The project was undertaken within the framework of the French epidemiological surveillance program EpiNano. This study allowed a first reliability assessment of the EpiNano method. However, to further validate this method a comparison with robust quantitative exposure measurement data is necessary.

Asbestos exposure and radiological abnormalities among maintenance and custodian workers in buildings with friable asbestos-containing materials.

OBJECTIVES: Few studies have been carried out to evaluate the respiratory effects of asbestos exposure of custodian and maintenance workers. METHODS: By a multicentre cross-sectional study, 277 custodian and maintenance employees working in buildings with friable asbestos-containing materials and 87 unexposed subjects were studied for radiological abnormalities by use of the International Labour Office (ILO) classification of radiographs of pneumoconiosis, in relation to parameters of asbestos exposure. RESULTS: The cumulative asbestos exposure index was generally low (fewer than 5 fibres/ml x years in 82.3% of exposed workers). On multivariate analysis, pleural thickening was significantly related to latency since onset of exposure to asbestos in exposed workers, after adjustment for age, body mass index and tobacco smoking. CONCLUSIONS: Asbestos exposure of custodian and maintenance employees in buildings with friable asbestos-containing materials might be associated with an excess of pleural thickening on chest X-rays.

Asbestos-related pleural diseases: dimensional criteria are not appropriate to differentiate diffuse pleural thickening from pleural plaques.

BACKGROUND: In the literature, the criteria used to define pleural plaques (PP) and diffuse pleural thickening (DPT) are very heterogeneous and often imprecise. A multicenter restropective study was conducted to assess the relevance of two radiographic definitions of DPT. METHODS: The study population consisted of 287 subjects with asbestos-related pleural thickening. Two definitions were used to characterize DPT on postero-anterior chest radiographs: definition 1: pleural thickening associated with obliteration of the costophrenic angle; definition 2: pleural thickening at least 5 mm wide, extending for more than one quarter of the chest wall. Prevalence of respiratory symptoms and pulmonary function tests were compared in the DPT and PP groups resulting from the two definitions of DPT. RESULTS: According to definition 1, 34 patients (11.8%) were classified in the DPT group. Prevalence of chronic sputum, dyspnea, and chest pain was significantly higher in this group than in the PP group. FEV(1), FVC, and TLC were significantly lower. The differences persisted after adjustment for confounding factors. According to definition 2,102 patients (36.6%) were classified in the DPT group. DPT and PP groups did not differ in terms of prevalence of respiratory symptoms, or pulmonary function tests. Agreement between readers was significantly better when using definition 1. CONCLUSIONS: Obliteration of costophrenic angle is a much more reliable sign than dimensional criteria to characterize DPT.