Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

Prevalence and Incidence of Multiple Sclerosis in the City of Biancavilla.

BACKGROUND: It is common that the epidemiology of multiple sclerosis (MS) varies with geography and ethnicity. Recent studies show a continuous growth of incidence and prevalence in Sicily, despite the controversial "latitude gradient theory." OBJECTIVES: The aim of our study is to ascertain incidence and prevalence rates of MS in the city of Biancavilla, Sicily, Southern Italy. METHOD: Case ascertainment approach and a clinical database collecting data of MS cases to Biancavilla, according to McDonald 2011 and Thompson 2018 criteria, from 1992 to 2018, have been used to the study. We further collected information regarding the familiarity of patients with Mesothelioma, highly incident in this geographic area. RESULTS: The results showed an increase of the mean annual incidence for the period 2012-2018 (16.8/100,000) compared to 1992-1996 (4.5/100,000), and a standardized incidence ratio of 1.41 (95% CI 0.74-2.45). On December 31, 2018, 70 patients suffering from definite MS and living in Biancavilla yielded a crude prevalence of 292.3 per 100,000 (198.2/100,000 for men; 380.7/100,000 for women) with a standardized morbidity ratio of 2.3 (95% CI 1.8-2.9). CONCLUSIONS: Our data confirmed Biancavilla is an area at high risk for MS, ascribable to increased survival, improved ascertainment, or maybe related to a genetic or environmental risk. At the time, any relation with mesothelioma was excluded.

Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report.

BACKGROUND: The immunohistochemical expression of aquaporin-1 (AQP1) in asbestos-related malignant pleural mesothelioma (MPM) is emerging as a useful prognostic indicator of improved survival. A significantly increased incidence of MPM in a small town in southern Italy was ascribed to exposure to fluoro-edenite (FE), a naturally occurring asbestos fiber. We investigated the immunohistochemical expression of AQP1 in patients affected by FE-related MPM; taking into consideration its suggested independent prognostic role, its possible correlation with clinicopathological parameters and patient outcome was also evaluated. METHODS: Ten patients were selected for this study, as neoplastic tissue blocks, clinical and follow-up data were available. The immunohistochemical overexpression of AQP1 was defined as ≥50% of tumor cells showing membranous staining. RESULTS: Six cases showed AQP1 expression in ≥50% of tumor cells; in this group, a significant association of AQP1 overexpression with an increased median overall survival (OS) of 26.3 months was observed. By contrast, four patients exhibited an AQP1 score of <50% of stained cells, with a shorter median OS of 8.9 months. CONCLUSIONS: The present study represents further confirmation of the hypothesized prognostic role of AQP1, which seems a reliable prognostic indicator.

Analysis of fibulin-3 after exposure to asbestos-like fibers.

A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.

Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.

Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in exposed group; whereas, 12 lung parenchymal involvement were registered in unexposed subjects. The RR for PPs is 6,74 CI 95% (4,47-9,58) p<0,0001 in the exposed population. These findings, suggested the urge to extend the screening on the possible involvement of the respiratory tract to all Biancavilla's population, particularly in those aged more than 30. Besides, it seems essential to start indoor monitoring Biancavilla's municipality.

Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite.

A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8-41µm in length and 0.4-1.39µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance.

FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study.

FBLN-3 has recently been proposed as a biomarker for malignant mesothelioma. A significantly increased standardized mortality rate from malignant mesothelioma has been reported in Biancavilla, Italy. Its cause has been identified in environmental exposure to fluoro-edenite. The aim of this study was to seek a correlation between plasma FBLN-3 concentration and pleural plaques in subjects exposed to fluoro-edenite and in a nonexposed control group. Pleural plaques was never detected in the control group, whereas it was found in 52% of exposed subjects. Median FBLN-3 concentrations were 12.96 and 5.29 ng/ml in the exposed and the control group, respectively (p < 0.001). FBLN-3 plasma levels exhibited a high predictive value for the presence of pleural plaques.

Detection of pleural plaques in workers exposed to inhalation of natural fluoro-edenite fibres.

Fluoro-edenite is a natural mineral species initially isolated in Biancavilla, Sicily. The fibres are similar in size and morphology to certain amphibolic asbestos fibres, the inhalation of which may cause chronic inflammation and cancer. Occupational asbestos exposure is known to be associated with pleural and lung diseases, including pleural plaques. The aim of this study was to report the pleural and lung parenchymal lesions detected by high-resolution computed tomography (HRCT) in a group of construction workers exposed to fluoro-edenite. Information regarding life habits and occupational history was collected from 43 workers enrolled into the study. The participants underwent physical examination, blood analysis, search for uncoated fibres and ferruginous bodies in the sputum, pulmonary function tests, including diffusion capacity for carbon monoxide (TLCO), and HRCT chest imaging. A general descriptive outcome analysis was also conducted; a prevalence ratio (PR) with 95% confidence interval and a two-tailed test P-value were calculated for pleural plaques using log-binomial regression, measuring plaque size and thickness, and cumulative exposure index (CEI). The mean values of the functional respiratory tests were within the normal range for all participants. A restrictive ventilatory defect was identified in two (5%) subjects and an obstructive ventilatory defect in three (7%) subjects. TLCO was reduced in two additional participants. Fibres were detected in 19 (44%) of subjects. Pleural involvement was documented in 39 (91%) workers, of whom 31 (72%) had bilateral plaques. Calcifications were detected in 25 (58%) of these participants. PR indicated a progressive increase in the risk of developing pleural lesions with rising CEI, i.e. length of exposure. The present findings demonstrate for the first time the presence of pleural plaques in the lungs of subjects exposed to fluoro-edenite fibres, and not to asbestos, through residing in Biancavilla and through their occupation.