Vermiculite Mine Research Articles

Asbestos-induced autoantibodies across Libby demographics

Asbestos-induced autoantibodies across Libby demographics Aiden Niblett, Jean Pfau, and Kinta Serve focus on asbestos-induced autoantibodies across different demographics in Libby. They emphasize the importance of understanding the impact of asbestos. Asbestos is a naturally occurring fibrous silicate mineral that has been used in construction due to its tensile strength and heat resistance. However, its small size and rigid shape allow it to enter deep into the respiratory tract upon inhalation, and exposures have been linked to serious lung diseases like pulmonary fibrosis and cancers. (1) The town of Libby, Montana, has a history of asbestos exposure due to a local vermiculite mine that operated from 1920-1990. Vermiculite mined from Libby and sold in products such as Zonolite Attic Insulation was found to be contaminated with Libby Amphibole (LA) asbestos, a unique mix of tremolite, winchite, and richterite fibers that is associated with severe lung diseases. (2)

Resíduo de mineração associado com bioinoculantes e esterco bovino na nutrição mineral e crescimento do milho

ABSTRACT Vermiculite mining residues, although of low solubility, contain nutrients such as calcium, magnesium, and potassium at concentrations that allow their agricultural use. Beneficial bacteria can increase the solubility of this waste and its efficiency. The objective of the present study was to evaluate the influence of bio-inoculation of vermiculite residue, associated with cattle manure, on the release of nutrients and initial growth of maize. A completely randomized design was performed in a greenhouse with seven treatments and four replications. The treatments were: T1 - soil without fertilization; T2 - soil fertilized with soluble sources of nutrients (conventional fertilization); T3 - application of vermiculite residue (VR); T4 - VR enriched with cattle manure (CM); T5 - VR + CM with Bacillus subtilis; T6 - VR + CM + B. amyloliquefaciens, and T7 - VR + CM +B. subtilis + B. amyloliquefaciens). Regardless of the use of cattle manure or beneficial microorganisms, vermiculite mining waste increased the availability of Ca and K in the soil, but was not able to match the soluble sources of nutrients. Mining waste associated with cattle manure and beneficial microorganisms (B. subtilis and B. amyloliquefaciens) increased microbial activity and enhanced the release of available calcium for maize. VR increased the growth and the dry mass production of maize compared to the non-fertilized soil, but was consistently inferior to conventional fertilizer.

Vermiculite Mining Waste Enriched with Elemental Sulfur as a Chemical Conditioner for Alkaline Saline Soils

ABSTRACT About 60 to 80% of the material extracted in vermiculite mining consists of unused waste, composed of minerals containing plant nutrients that can chemically improve the soil. The objective was to evaluate the potential of vermiculite mining residue associated with elemental sulfur in the chemical attributes of two alkaline saline soils. Two experiments were carried out in a completely randomized design in a 6 × 2 factorial scheme with four replications. In the first experiment, six doses of vermiculite waste enriched with 5% (50 g kg−1) elemental sulfur (0, 10, 20, 30, 40 and 50 t ha−1), and two alkaline soils (sodic soil and other non-sodic) were tested. In the second experiment, six doses of elemental sulfur (0; 0.25; 0.50; 0.75; 1.0; 1.25 g dm−3) and two soils (sodic soil and other non-sodic) were tested. At 30 and 105 days after soil incubation, the hydrogenionic potential (pH) values, electrical conductivity, concentrations of available sulfate (SO4 −2), phosphorus (P), and exchangeable calcium (Ca2+), potassium (K+) and sodium (Na+) were determined. The vermiculite waste associated with elemental sulfur can be used as an alternative source of K+ and contribute to reduce the pH of the alkaline soil and adding Ca2+ and SO4 −2 to the soil. However, in soils with poor drainage, this compound should be used with caution due to the risk of soil sodification. Elemental sulfur only, reduced the pH and increased the levels of Ca2+ and SO4 −2 in both studied soils and reduced levels of Na+ in sodic soil after 105 days of incubation.

INDUSTRIAL MINERALS OF NORTH EUROPEAN RUSSIA

The importance of North European Russia’s industrial minerals for the country’s mineral raw materials economy is shown with regard for the fact that a large part of the territory is in the Arctic Zone. The history of the study and use of mineral resources in northern parts of the Old Russian state, from the start of large-scale mica and salt production and pearl harvesting to the industrial appraisal and mining of muscovite, phlogopite, vermiculite, feldspar and baddeleyite deposits, and the launching of the large-scale production of apatitnepheline, diamond, salt, barite, shungite and other commercial minerals. It is stressed that the structure of continental North European Russia has been forming through a long geological evolution from 3.5 Ga to the present day. Geologically, it is composed of the East European Platform basement (Fennoscandian Shield) consisting of Precambrian rocks subsiding gently under the sedimentary cover of the Russian Plate, the Timan-Pechora Platform with a Riphean basement, and the Timan-Pechora Platform lying farther eastwards. The mineral genesis of the Precambrian and the Phanerozoic provinces displays a contrasting pattern. The industrial mineral deposits and largescale occurrences of North European Russia, differing in genesis and age, are reviewed and a sketch map of their distribution is supplemented. North Russia’s mineral potential could be enlarged by the prospecting, appraisal and mining of some new localities.

Analysis of autoantibody profiles in two asbestiform fiber exposure cohorts

ABSTRACT An increased risk for Systemic Autoimmune Diseases (SAID) was reported in the population of Libby, Montana, where extensive exposure to asbestiform amphiboles occurred through mining and use of asbestiform fiber-laden vermiculite. High frequencies of antinuclear autoantibodies (ANA) were detected in individuals and mice exposed to Libby Asbestiform Amphiboles (LAA). Among the 6603 individuals who have undergone health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), the frequencies of rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and systemic sclerosis are significantly higher than expected prevalence in the United States. While these data support the hypothesis that LAA can trigger autoimmune responses, evidence suggests that chrysotile asbestos does not. Serological testing was therefore performed in subjects exposed to LAA or predominantly chrysotile (New York steamfitters) using multiplexed array technologies. Analyses were performed in order to determine a) autoantibody profiles in each cohort, and b) whether the two populations could be distinguished through predictive modeling. Analysis using perMANOVA testing confirmed a significant difference between autoantibody profiles suggesting differential pathways leading to autoantibody formation. ANA were more frequent in the LAA cohort. Specific autoantibodies more highly expressed with LAA-exposure were to histone, ribosomal P protein, Sm/Ribonucleoproteins, and Jo-1 (histidyl tRNA synthetase). Myositis autoantibodies more highly expressed in the LAA cohort were Jo-1, PM100, NXP2, and Mi2a. Predictive modeling demonstrated that anti-histone antibodies were most predictive for LAA exposure, and anti-Sm was predictive for the steamfitters’ exposure. This emphasizes the need to consider fiber types when evaluating risk of SAID with asbestos exposure.

Measuring EMPs in the lung what can be measured in the lung: Asbestiform minerals and cleavage fragments

Asbestos mineral fibers have been associated with the development of a variety of diseases in humans and experimental animals, including asbestosis, lung cancer, and mesothelioma. Asbestos includes several mineral types divided into two mineral groups, serpentine and amphibole forms. Chrysotile is the serpentine mineral classified as asbestos, whereas the amphiboles include amosite, crocidolite, tremolite, actinolite and anthophyllite.There are a number of mineral fibers that occur with asbestiform morphology and that have been associated with various asbestos-induced diseases. These include the Libby amphiboles (associated with a vermiculite mine northwest of Libby, MT), erionite (in Turkey and North America), fluoro-edenite (in Sicily), and perhaps balangeroite (in Italy). In addition, each of the asbestos minerals occurs in a non-fibrous form, and these may occur as cleavage fragments that satisfy the definition for a fiber, i.e., particles with an aspect ratio of at least 3:1 and roughly parallel sides. Cleavage fragments of non-asbestiform minerals have not been associated with asbestos-induced diseases nor are these minerals regulated by the Occupational Safety and Health Administration.Finally, there are a number of other mineral species which can occur in human lung samples that satisfy the definition for a fiber as given above. These similarly have not been associated with asbestos-induced diseases. All of these various minerals satisfying the definition for a fiber can be referred to as elongated mineral particles (EMP). It is the purpose of this presentation to discuss the role of scanning electron microscopy (SEM) equipped with an energy dispersive x-ray analyzer (EDXA) in the detection and classification of EMP in human lung samples.

Case series: rheumatological manifestations attributed to exposure to Libby Asbestiform Amphiboles

ABSTRACTAn increased risk for Systemic Autoimmune Diseases (SAID) has been reported in Libby, Montana, where extensive exposures to fibrous amphiboles occurred due to mining and use of asbestos-laden vermiculite. In addition, positive antinuclear autoantibody tests are associated with exposure to Libby Asbestiform Amphiboles (LAA) in both humans and mice. Among 6603 subjects who underwent health screening at the Center for Asbestos Related Diseases (CARD, Libby MT), 13.8% were diagnosed with an autoimmune disease, with prevalence values for the most common SAID being significantly higher than expected in the United States. Among the CARD screening population, serological and clinical profiles are diverse, representing symptoms and autoantibodies reflective of systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis, and other rheumatic syndromes, including undifferentiated connective tissue disease (UCTD). Based upon screening of medical records by physicians with rheumatology expertise, the evolving nature of rheumatological disease in these patients is often atypical, with mixed diagnostic criteria and with a 1:1 male-to-female ratio. Through the Libby Epidemiology Research Program, cases were identified that illustrate clinical autoimmune outcomes with LAA exposure. Our goal was to better characterize SAID in Libby, MT in order to improve recognition of autoimmune outcomes associated with this exposure. In view of recent discoveries of widespread exposure to fibrous minerals in several areas of the U.S. and globally, it is critical to evaluate rheumatologic manifestations in other cohorts so that screening, surveillance, and diagnostic procedures are able to detect and recognize potential autoimmune outcomes of asbestos exposure.Abbreviations: ANA, antinuclear autoantibody; ARD, Asbestos-Related Diseases; ATSDR, Agency for Toxic Substances & Disease Registry; CARD, Center for Asbestos Related Diseases; CCP, Cyclic citrullinated peptide antibody; CREST, limited cutaneous form of scleroderma; CT, computed tomography; DIP, Distal Interphalangeal Joint; DLCO, Diffusing Capacity of the Lung for CO2; DMARD, Disease Modifying Anti-Rheumatic Drugs; ENA, Extractable Nuclear Antigen antibodies; FVC, Forced Vital Capacity; LAA, Libby Asbestiform Amphiboles; LERP, Libby Epidemiology Research Program; MCP, Metacarpal Phalangeal Joint; PIP, Proximal Interphalangeal Joint; PIP, rheumatoid arthritis; RV, Residual Volume; SAID, Systemic autoimmune diseases; SLE, systemic lupus erythematosus; SSc, Systemic Sclerosis; TLC, Total Lung Capacity

Six Years of Asbestos Health Screening Results in Libby, Montana

SESSION TITLE: Environmental and Occupational Health SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Libby, Montana in 2009 became the first and only EPA-declared public health emergency which led to Affordable Care Act (ACA) funding for free asbestos health screening. Libby was the site of a vermiculite mine that operated between 1919 and 1990. The vermiculite was contaminated with fibers called Libby amphibole (LA) asbestos. The Center for Asbestos Related Disease (CARD) has been conducting screening under the ACA since July 2011. Results from these free asbestos health screenings will be presented. METHODS: Free screenings include exposure history, health history, respiratory symptoms, and tobacco use history, a spirometry and PA CXR, and a medical provider visit. In many instances, a chest CT without contrast for confirmation of asbestos related abnormalities is also ordered. Smoking cessation and fecal occult blood testing are also offered. Eligibility for screening requires individuals to have lived, worked or played in the Libby, MT area for at least 6 months at least 10 years prior to being screened to target those with sufficient exposure and latency. Once asbestos related abnormalities are identified on CT, individuals are considered diagnosed and no longer eligible for screening. CXRs are sent for B reading and CT scans are sent to be read by thoracic radiologists with expertise in identification of asbestos related abnormalities. RESULTS: 4,466 B reads were returned and asbestos related abnormalities were identified on 431 of them (9.7%). 3,192 radiologist’s CT reads were returned and asbestos related abnormalities were identified on 1,204 of them (37.7%). Based on positive CT reads, 27% of screenings were considered positive for ARPD. Of the 27% (1,204 of 4,466), 441 had abnormal spirometry, 273 were current smokers, and 974 reported respiratory symptoms such as chronic cough and dyspnea on exertion. In addition 10 lung masses were identified in the screening population. The vast majority of individuals who underwent screening reported no occupational exposed to LA. CONCLUSIONS: Ongoing screening in Libby, MT along with EPA cleanup of the Libby asbestos superfund site has been ongoing since 2000 and continues today. Identification of asbestos related abnormalities in this population continues with 27% of the screenings resulting in identification of asbestos related abnormalities in last 6 years. Most reported exposures are nonoccupational in this population. CLINICAL IMPLICATIONS: LA exposure may be occurring nationwide due to attic insulation in millions of homes. DISCLOSURE: The following authors have nothing to disclose: Tracy McNew, Charles Black No Product/Research Disclosure Information

Asbestiform and non-asbestiform morphologies in a talc and vermiculite mine from the province of Córdoba (Argentina): a case study

In this work, a talc and vermiculite mine from the province of Cordoba (Argentina) was investigated with special emphasis on the occurrence of asbestiform and non-asbestiform phases. The meta-ultramafic rock was studied by a multimethodological approach, complementing field studies with petrographic-mineralogical, compositional and morphological analyses. Samples were examined by stereomicroscopy, polarizing light microscopy, SEM–EDS, XRD, DSC-TGA and FTIR. Complementary, compositional and textural analyses were performed with FE-SEM–EDS and EPMA. Talc-rich veins with a laminar and fibrous appearance were at first recognized. However, the fibrous morphology observed both in the field and by microscopy is due to an apparent habit because of the sample orientation. To avoid erroneous interpretations, studies by secondary electron images (SEM) are fundamental to carrying out this type of analysis. Tremolite was identified in different zones of the outcrop; however, only ~40% of the crystals located in the vermiculite zone have dimensions to be considered as asbestiform fibres in the range of respirable particles. In these types of complex deposits affected by superimposed metamorphic, igneous and deformational events, multimethodological approaches are necessary to develop models of occurrence of asbestiform morphologies that may be applicable to other with similar characteristics.

The Effects of Pleural Plaques on Longitudinal Lung Function in Vermiculite Miners of Libby, Montana

BackgroundThis study was conducted to assess associations of pleural plaques (PP) and longitudinal lung function in vermiculite miners of Libby, Montana who are occupationally exposed to asbestos. High-resolution computed tomography (HRCT) was used to identify asbestos-related findings in former Libby vermiculite miners. We investigated annual lung function decline in miners with PP only and compared them to miners with normal HRCT findings. Materials and MethodsHRCTs from 128 miners were categorized into the following 4 diagnostic groups: (1) normal computed tomography scan (n = 9); (2) PP only (n = 72); (3) PP and interstitial fibrosis (n = 26) and (4) additional HRCT abnormalities (n = 21) such as rounded atelectasis, diffuse pleural thickening, pleural effusions or pulmonary nodules or tumor >1cm in diameter. Random intercept and slope linear mixed-effect regression models identified differences in lung function decline between miners with asbestos-associated outcomes and those with normal HRCT. Models were adjusted for follow-up time, body mass index, smoking status, latent exposure period and employment years. Interactions for smoking status with age and smoking status with pleural plaque severity were examined. ResultsMiners with PP only did not have an accelerated decline in lung function between 40 and 80 years. Miners with PP and additional HRCT abnormalities displayed significantly accelerated declines in forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide (P = 0.05 and P < 0.01, respectively). Plaque severity did not affect lung function decline. However, smokers with extensive plaques displayed accelerated loss in diffusing capacity of the lungs for carbon monoxide and forced expiratory volume in 1 second when compared to nonsmoking miners with mild plaque formation. ConclusionsPP alone did not significantly affect lung function decline in vermiculite miners of Libby, Montana.

Libby: the long legacy of a public health disaster

Libby: the long legacy of a public health disaster

Mortality from asbestos-associated disease in Libby, Montana 1979\u20132011

Research on asbestos exposure in Libby, MT, has focused on occupational exposure in vermiculite mining and processing, but less attention has been paid to asbestos-related mortality among community members without vermiculite mining occupational history. Our study reports on asbestos-related mortality in Libby over 33 years (1979–2011) while controlling for occupational exposure. We calculated sex-specific 33-year standardized mortality ratios (SMRs) for Libby residents who died from 1979 to 2011 with an asbestos-related cause of death. Decedent address at time of death was geocoded to confirm inclusion in the Libby County Division. We controlled for past W.R. Grace employment by including and then removing them from the SMR analysis. Six hundred and ninety-four decedents were identified as having at least one asbestos-related cause of death and residing in our study area boundary. Statistically significant (P<0.05) 33-year SMRs, both before and after controlling for W.R. Grace employment, were found for: male and female non-malignant respiratory diseases, female COPD, and asbestosis for both sexes combined. Eighty-five men and two women were matched to employment records. We observed elevated asbestos-related mortality rates among males and females. SMR results for asbestosis were high for both sexes, even after controlling for past W.R. Grace employment. These results suggest that the general population may be experiencing asbestos-related effects, not just former vermiculite workers. Additional research is needed to determine whether SMRs remain elevated after controlling for secondary exposure, such as living with vermiculite workers.

Where Occupation and Environment Overlap: US Forest Service Worker Exposure to Libby Amphibole Fibers

The National Institute for Occupational Safety and Health (NIOSH) conducted an evaluation of exposures to asbestiform amphibole, known as Libby Amphibole (LA), to personnel from the US Department of Agriculture-Forest Service (USFS) working in the Kootenai National Forest near a former vermiculite mine close to Libby, Montana. LA is associated with vermiculite that was obtained from this mine; mining and processing over many years have resulted in the spread of LA into the surrounding Kootenai Forest where it has been found in tree bark, soil, and forest floor litter. As a result of this and other contamination, Libby and surrounding areas have been designated a “Superfund” site by the US Environmental Protection Agency (EPA). This article describes the application of EPA methods for assessing cancer risks to NIOSH sampling results. Phase-contrast microscopy for airborne asbestos fiber evaluation was found to be less useful than transmission electron microscopy in the presence of interfering organic (plant) fibers. NIOSH Method 7402 was extended by examination of larger areas of the filter, but fiber counts remained low. There are differences between counting rules in NIOSH 7402 and the ISO method used by EPA but these are minor in the context of the uncertainty in concentration estimates from the low counts. Estimates for cancer risk are generally compatible with those previously estimated by the EPA. However, there are limitations to extrapolating these findings of low risk throughout the entire area and to tasks that were not evaluated.

Diagnóstico espaço-temporal das áreas impactadas pela MPL - Mineração Pedra Lavrada (Santa Luzia-PB), na extração de vermiculita

A mineração é um dos setores básicos da economia, contribuindo de forma decisiva para o desenvolvimento do país, desde que seja operada com responsabilidade social e ambiental. O presente estudo tem como objetivo diagnosticar o espaço-temporal da área degradada pela extração de Vermiculita, e propor adequar a atividade no PRAD apresentado pela empresa. O trabalho foi desenvolvido com o apoio da Empresa MPL - Mineração Pedra Lavrada Ltda, localizada no Município de Santa Luzia-PB, na Região do Seridó Ocidental Paraibano, e com os resultados sido coletados em outubro de 2014. Para a realização do estudo avaliou-se a área nos seguintes aspectos: a época em que a área foi impactada e o tipo de impacto causado. Após estes estudos, foi feita a quantificação da área alterada pela atividade minerária, para posteriormente propor a recomposição do passivo gerado, utilizando as técnicas de geoprocessamento e sensoriamento remoto para chegar aos resultados finais.

Pleural Plaques and Their Effect on Lung Function in Libby Vermiculite Miners

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Multiple pathway asbestos exposure assessment for a Superfund community.

Libby, MT, USA, was the home to workers at a historical vermiculite mining facility and served as the processing and distribution center for this industrial product that was contaminated with amphibole asbestos. Several pathways of environmental asbestos exposure to the general population have been identified. The local clinic and health screening program collects data from participants on past occupational and environmental exposures to vermiculite and asbestos. Health studies among this population have demonstrated associations between amphibole exposure and health outcomes, but critical questions regarding the nature and level of exposure associated with specific outcomes remain unanswered. The objective of this study was to develop a comprehensive exposure assessment approach that integrates information on individuals' contact frequency with multiple exposure pathways. For 3031 participants, we describe cumulative exposure metrics for environmental exposures, occupational exposures, and residents' contact with carry-home asbestos from household workers. As expected, cumulative exposures for all three occupational categories were higher among men compared with women, and cumulative exposures for household contact and environmental pathways were higher among women. The comprehensive exposure assessment strategies will advance health studies and risk assessment approaches in this population with a complex history of both occupational and environmental asbestos exposure.

In vitro determinants of asbestos fiber toxicity: effect on the relative toxicity of Libby amphibole in primary human airway epithelial cells

BackgroundAn abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples.MethodsPrimary human airway epithelial cells (HAEC) were exposed to two different LA samples as well as standard amphibole reference samples. Analysis of the samples included a complete particle size distribution analysis, calculation of surface area by electron microscopy and by gas adsorption and quantification of surface-conjugated iron and hydroxyl radical production by the fibers. Interleukin-8 mRNA levels were quantified by qRT-PCR to measure relative pro-inflammatory response induced in HAEC in response to amphibole fiber exposure. The relative contribution of key physicochemical determinants on the observed pro-inflammatory response were also evaluated.ResultsThe RTI amosite reference sample contained the longest fibers and demonstrated the greatest potency at increasing IL-8 transcript levels when evaluated on an equal mass basis. The two LA samples and the UICC amosite reference sample consisted of similar particle numbers per milligram as well as similar particle size distributions and induced comparable levels of IL-8 mRNA. A strong correlation was observed between the elongated particle (aspect ratio ≥3:1) dose metrics of length and external surface area. Expression of the IL-8 data with respect to either of these metrics eliminated the differential response between the RTI amosite sample and the other samples that was observed when HAEC were exposed on an equal mass basis.ConclusionsOn an equal mass basis, LA is as potent as the UICC amosite reference sample at inducing a pro-inflammatory response in HAEC but is less potent than the RTI amosite sample. The results of this study show that the particle length and particle surface area are highly correlated metrics that contribute significantly to the toxicological potential of these amphibole samples with respect to the inflammogenic response induced in airway epithelial cells.

Asbestos-associated mesothelial cell autoantibodies promote collagen deposition in vitro

Fibrosis, characterized by excessive collagen protein deposition, is a progressive disease that can fatally inhibit organ function. Prolonged exposure to pathogens or environmental toxicants such as asbestos can lead to chronic inflammatory responses associated with fibrosis. Significant exposure to amphibole asbestos has been reported in and around Libby, Montana due to local mining of asbestos-contaminated vermiculite. These exposures have been implicated in a unique disease etiology characterized predominantly by pleural disorders, including fibrosis. We recently reported the discovery of mesothelial cell autoantibodies (MCAAs) in the sera of Libby residents and demonstrated a positive and significant correlation with pleural disease; however, a mechanistic link was not determined. Here we demonstrate that MCAAs induce pleural mesothelial cells to produce a collagen matrix but do not affect production of the pro-inflammatory cytokine tumor growth factor-β. While autoantibodies commonly induce a pro-fibrotic state by inducing epithelial–mesenchymal transition (EMT) of target cells, we found no evidence supporting EMT in cells exposed to MCAA positive human sera. Although implicated in other models of pulmonary fibrosis, activity of the protein SPARC (secreted protein, acidic and rich in cysteine) did not affect MCAA-induced collagen deposition. However, matrix formation was dependent on matrix metalloproteinase (MMP) activity, and we noted increased expression of MMP-8 and -9 in supernatants of mesothelial cells incubated with MCAA positive sera compared to control. These data suggest a mechanism by which MCAA binding leads to increased collagen deposition through altering MMP expression and provides an important mechanistic link between MCAAs and asbestos-related, autoimmune-induced pleural fibrosis.

Aspects of exposure measurement error in epidemiologic cohort analyses using the Libby amphibole asbestos worker cohort. Influence of changes in exposure assess

Background: The extent of employees’ work history covered by measured exposures has been shown, using meta-analysis, to be an important predictor of summary effect measures for lung cancer mortality risk associated with asbestos exposure. We studied lung cancers associated with exposures at the asbestos-contaminated vermiculite mine in Libby, Montana, a major supplier of vermiculite demand during the 20th century. The cohort of workers includes those hired after 1935 with mortality follow-up through 2006. The associated job exposure matrix is based on measured fiber exposures from 1968-1982. Prior to 1968, exposures were largely estimated based on extrapolation of job-specific exposures in the late 1960’s backwards in time to 1935 with an expert consideration of changes in workplace processes over time. Aims: To evaluate the influence of exposure measurement error on lung cancer potency estimates. Methods: We estimated the effect of occupational exposures on lung cancer mortality using the time-varying Cox regression model for different cohorts depending on worker’s dates of hire in order to gauge the impact of potential exposure measurement error over time. Supplemental analyses assessed the inclusion of the percentage of work-history covered by measured exposure as a time-varying covariate. Results: Compared to previous published analyses based on the cohort of workers hired after 1935, when exposures assignments from the job exposure matrix were based on measured exposures only 47% of the time, our analyses based on higher quality exposure data from workers hired after 1959, when occupational exposures were predominantly based on measured exposures (85%), yielded an effect size as much as 3.6 times higher. Conclusions: Future occupational cohort analyses should continue to refine retrospective exposure assessment methods and explore new methods to control for changes in the quality of exposure estimates over time. Disclaimer: This abstract does not necessarily reflect EPA policy.

Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA ( p = 0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects ( p = 0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.