Threshold Regression Models Adapted to Case-Control Studies, and the Risk of Lung Cancer Due to Occupational Exposure to Asbestos in France

Asbestos has been known for many years as a powerful carcinogen. Our purpose is quantify the relationship between an occupational exposure to asbestos and an increase of the risk of lung cancer. Furthermore, we wish to tackle the very delicate question of the evaluation, in subjects suffering from a lung cancer, of how much the amount of exposure to asbestos explains the occurrence of the cancer. For this purpose, we rely on a recent French case-control study. We build a large collection of threshold regression models, data-adaptively select a better model in it by multi-fold likelihood-based cross-validation, then fit the resulting better model by maximum likelihood. A necessary preliminary step to eliminate the bias due to the case-control sampling design is made possible because the probability distribution of being a case can be computed beforehand based on an independent study. The implications of the fitted model in terms of a notion of maximum number of years of life guaranteed free of lung cancer are discussed

Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity.

International audienceThe fibrogenicity and carcinogenicity of asbestos fibers are dependent on several fiber parameters including fiber dimensions. Based on the WHO (World Health Organization) definition, the current regulations focalise on long asbestos fibers (LAF) (Length: L ≥ 5 μm, Diameter: D  3). However air samples contain short asbestos fibers (SAF) (L < 5 μm). In a recent study we found that several air samples collected in buildings with asbestos containing materials (ACM) were composed only of SAF, sometimes in a concentration of ≥10 fibers.L-1. This exhaustive review focuses on available information from peer-review publications on the size-dependent pathogenetic effects of asbestos fibers reported in experimental in vivo and in vitro studies. In the literature, the findings that SAF are less pathogenic than LAF are based on experiments where a cut-off of 5 μm was generally made to differentiate short from long asbestos fibers. Nevertheless, the value of 5 μm as the limit for length is not based on scientific evidence, but is a limit for comparative analyses. From this review, it is clear that the pathogenicity of SAF cannot be completely ruled out, especially in high exposure situations. Therefore, the presence of SAF in air samples appears as an indicator of the degradation of ACM and inclusion of their systematic search should be considered in the regulation. Measurement of these fibers in air samples will then make it possible to identify pollution and anticipate health risk

Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

International audienceABSTRACT: BACKGROUND: Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. METHODS: On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 mug) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1beta (IL-1beta), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry. RESULTS: TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1beta and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema. CONCLUSIONS: TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages

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 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

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

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

CT scan screening is associated with increased distress among subjects of the APExS

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the psychological consequences of HRCT scan screening in retired asbestos-exposed workers.</p> <p>Methods</p> <p>A HRCT-scan screening program for asbestos-related diseases was carried out in four regions of France. At baseline (T1), subjects filled in self-administered occupational questionnaires. In two of the regions, subjects also received a validated psychological scale, namely the psychological consequences questionnaire (PCQ). The physician was required to provide the subject with the results of the HRCT scan at a final visit. A second assessment of psychological consequences was performed 6 months after the HRCT-scan examination (T2). PCQ scores were compared quantitatively (t-test, general linear model) and qualitatively (chi²-test, logistic regression) to screening results. Multivariate analyses were adjusted for gender, age, smoking, asbestos exposure and counseling.</p> <p>Results</p> <p>Among the 832 subjects included in this psychological impact study, HRCT-scan screening was associated with a significant increase of the psychological score 6 months after the examination relative to baseline values (8.31 to 10.08, p < 0.0001, t-test). This increase concerned patients with an abnormal HRCT-scan result, regardless of the abnormalities, but also patients with normal HRCT-scans after adjustment for age, gender, smoking status, asbestos exposure and counseling visit. The greatest increase was observed for pleural plaques (+3.60; 95%CI [+2.15;+5.06]), which are benign lesions. Detection of isolated pulmonary nodules was also associated with a less marked but nevertheless significant increase of distress (+1.88; 95%CI [+0.34;+3.42]). However, analyses based on logistic regressions only showed a close to significant increase of the proportion of subjects with abnormal PCQ scores at T2 for patients with asbestosis (OR = 1.92; 95%CI [0.97-3.81]) or with two or more diseases (OR = 2.04; 95%CI [0.95-4.37]).</p> <p>Conclusion</p> <p>This study suggests that HRCT-scan screening may be associated with increased distress in asbestos-exposed subjects. If confirmed, these results may have consequences for HRCT-scan screening recommendations.</p

Contribution de deux tests immunopharmacologiques dans l'exploration d'allergies respiratoires professionnelles

Une étude rétrospective a été conduite chez 169 patients explorés entre 1995 et 2007 dans un Service de Pneumologie et de Pathologie Professionnelle d Ile de France, pour suspicion d asthme professionnel et/ou de rhinite professionnelle. Cinq allergènes ou familles d allergènes ont été évalués : les ammoniums quaternaires, les amines aliphatiques, le latex, le glutaraldéhyde et les persulfates. Le test de référence utilisé était une probabilité clinique d asthme professionnel ou de rhinite professionnelle, liée à un allergène professionnel précis, déterminée par 2 experts en pathologie professionnelle, de manière rétrospective, d après l ensemble des informations cliniques et paracliniques des dossiers des patients. Dans notre étude les résultats des tests de transformation lymphoblastique (TTL) et des tests d histaminolibération (THL), vis-à-vis de ces 5 allergènes montrent des performances contrastées en fonction des allergènes. Dans l ensemble, la sensibilité retrouvée est faible (inférieure à 50%). La spécificité est élevée pour plusieurs allergènes ou familles d allergènes : les ammoniums quaternaires, les amines aliphatiques et le latex. Concernant le glutaraldéhyde et les persulfates, les tests sont peu performants. Pour les amines aliphatiques le THL offre une spécificité de 100%, ainsi qu une valeur prédictive positive de 100% dans cette série, mais la sensibilité est faible (44%). Si le TTL apparaît peu utile dans cette étude, le THL aide à affirmer le diagnostic d allergie respiratoire professionnelle à certaines amines aliphatiques lorsqu il est positif. Il apparaît important de poursuivre les efforts de mise au point de tests biologiques aidant à l exploration étiologique des allergies respiratoires professionnelles.A retrospective study was conducted among 169 patients referred to a Chest and Occupational Diseases Department in Paris area between 1995 and 2007, for a suspicion of occupational asthma and/or occupational rhinitis. Five allergens or families of allergens have been investigated: latex, glutaraldehyde, persulfates, quaternary ammoniums and aliphatic amines. The reference test was a clinical probability of occupational asthma or occupational rhinitis, due to a specific occupational allergen retrospectively established by two experts in occupational disease, according to available clinic and paraclinic informations of patient records. In our study, the results of lymphocyte transformation tests (LTT) and histamine release tests (HRT) towards these five allergens havecontrasting performances. When all allergens are considered, the average sensibility is quite small (less than 50%). Nevertheless, tht specificity is quite high for several allergens or allergen families: quaternary ammoniums, latex and aliphatic amines. Regarding glutaraldehyde and persulfates, tests are inefficient. For aliphatic amines, the HRT enables a specificity equal to 100%, and a positive predictive value of 100% in this sample of patients while the sensibility is low (44%). If the LTT is not very useful in this study, the HRT enables to conclude on the occupational allergy diagnosis due to aliphatic amines when it is positive. At the end of our study, it seems crucial to carry on efforts to build or improve biologic tests to help the diagnosis of respiratory occupational allergy.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF