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The pathology of coal workers' pneumoconiosis (CWP) and its most severe form-progressive massive fibrosis (PMF)-in US coal miners has changed in recent years. Severe disease is occurring in younger miners and has been linked to an increase in silica dust exposure. To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. This study is a retrospective expert classification of lung tissue from 85 historical and contemporary coal miners with PMF. Significant pathologic features were scored by using a standardized instrument with consensus achieved for major findings, including newly defined categories of PMF as coal-type, mixed-type, and silica-type. Pathologic features associated with silica dust exposure, including silica-type PMF, mineral dust alveolar proteinosis (MDAP), and immature (early stage) silicotic nodules, were increased in contemporary miners. Detailed descriptions of the pathology of contemporary CWP with illustrative figures are provided. Silica-related pathologies are more common in contemporary miners. Severe forms of CWP can be detected by subtyping PMF lesions (if present) or by identification of mature and immature silicotic nodules, coal mine dust-related alveolar proteinosis, and severe inflammation in coal miners' lungs. Silica-type PMF cases showed significantly higher levels of MDAP than either mixed- or coal-type PMF (P < .001). High profusion of birefringent silica/silicate particles was observed more frequently in cases with immature (early stage) silicotic nodules (P = .04). Severe inflammation was also significantly increased in contemporary miners (P = .03). Our findings underscore the urgent need to revise current exposure limits and monitoring of respirable crystalline silica in US coal mines.

BackgroundThe development of organ fibrosis after injury requires activation of transforming growth factor β1 which regulates the transcription of profibrotic genes. The systemic administration of a proteasomal inhibitor has been reported to prevent the development of fibrosis in the liver, kidney and bone marrow. It is hypothesised that proteasomal inhibition would prevent lung and skin fibrosis after injury by inhibiting TGF-β1-mediated transcription.MethodsBortezomib, a small molecule proteasome inhibitor in widespread clinical use, was administered to mice beginning 7 days after the intratracheal or intradermal administration of bleomycin and lung and skin fibrosis was measured after 21 or 40 days, respectively. To examine the mechanism of this protection, bortezomib was administered to primary normal lung fibroblasts and primary lung and skin fibroblasts obtained from patients with idiopathic pulmonary fibrosis and scleroderma, respectively.ResultsBortezomib promoted normal repair and prevented lung and skin fibrosis when administered beginning 7 days after the initiation of bleomycin. In primary human lung fibroblasts from normal individuals and patients with idiopathic pulmonary fibrosis and in skin fibroblasts from a patient with scleroderma, bortezomib inhibited TGF-β1-mediated target gene expression by inhibiting transcription induced by activated Smads. An increase in the abundance and activity of the nuclear hormone receptor PPARγ, a repressor of Smad-mediated transcription, contributed to this response.ConclusionsProteasomal inhibition prevents lung and skin fibrosis after injury in part by increasing the abundance and activity of PPARγ. Proteasomal inhibition may offer a novel therapeutic alternative in patients with dysregulated tissue repair and fibrosis.

ObjectivesTo investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry.MethodsWith ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher’s exact tests and logistic regression.ResultsAmong 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity.ConclusionsFindings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

ObjectivesThe natural history of coal workers’ pneumoconiosis (CWP) after cessation of exposure remains poorly understood.MethodsWe characterised the development of and progression to radiographic progressive massive fibrosis (PMF) among former US coal miners who applied for US federal benefits at least two times between 1 January 2000 and 31 December 2013. International Labour Office classifications of chest radiographs (CXRs) were used to determine initial and subsequent disease severity. Multivariable logistic regression models were used to identify major predictors of disease progression.ResultsA total of 3351 former miners applying for benefits without evidence of PMF at the time of their initial evaluation had subsequent CXRs. On average, these miners were 59.7 years of age and had 22 years of coal mine employment. At the time of their first CXR, 46.7% of miners had evidence of simple CWP. At the time of their last CXR, 111 miners (3.3%) had radiographic evidence of PMF. Nearly half of all miners who progressed to PMF did so in 5 years or less. Main predictors of progression included younger age and severity of simple CWP at the time of initial CXR.ConclusionsThis study provides further evidence that radiographic CWP may develop and/or progress absent further exposure, even among miners with no evidence of radiographic pneumoconiosis after leaving the industry. Former miners should undergo regular medical surveillance because of the risk for disease progression.

ObjectivesPrevious radiologic and histopathologic studies suggest respirable crystalline silica (RCS) overexposure has been driving the resurgence of pneumoconiosis among contemporary US coal miners, with a higher prevalence of severe disease in Central Appalachia. We sought to better understand RCS exposure among US underground coal miners.MethodsWe analysed RCS levels, as measured by respirable quartz, from coal mine dust compliance data from 1982 to 2021.ResultsWe analysed 322 919 respirable quartz samples from 5064 US underground coal mines. Mean mine-level respirable quartz percentage and mass concentrations were consistently higher for Central Appalachian mines than the rest of the USA. Mean mine-level respirable quartz mass concentrations decreased significantly over time, from 0.116 mg/m3 in 1982 to as low as 0.017 mg/m3 for Central Appalachian mines, and from 0.089 mg/m3 in 1983 to 0.015 mg/m3 in 2020 for the rest of the USA. Smaller mine size, location in Central Appalachia, lack of mine safety committee and thinner coal seams were predictive of higher respirable quartz mass concentrations.ConclusionsThese data substantially support the association between RCS overexposure and the resurgence of coal workers’ pneumoconiosis in the USA, particularly in smaller mines in Central Appalachia.

IntroductionPrevious studies suggest respirable crystalline silica (RCS) is an important driver of resurgent pneumoconiosis among US coal miners. Although greater attention has been focused on dust exposures in underground coal miners, surface miners are also at risk of severe disease. This study explores RCS exposure in this population.MethodsWe analysed 91 950 respirable quartz samples from 4127 US surface coal mines from 1982 to 2023. We calculated the geometric mean of respirable quartz concentration for each mine-year combination. Then, for each calendar year, we averaged the geometric means across all mines. We used generalised estimating equation models with a natural logarithm link function and Poisson distribution to evaluate the marginal effects of mine characteristic variables on the mass concentration of respirable quartz based on individual dust sample results.ResultsDrillers and bulldozer operators had annual mean respirable quartz exposures as high as 0.58 and 0.32 mg/m3, respectively, while other occupations combined had exposure of 0.08 mg/m3. The mean mine-level respirable quartz mass concentrations decreased substantially over time for all three occupation groups. Drillers or bulldozer operators, mine location in Central Appalachia and lack of a mine safety committee were predictive of higher respirable quartz mass concentrations.ConclusionsThese data demonstrate exceptionally high RCS overexposures among certain groups of surface coal miners, particularly drillers and bulldozer operators in the 1980s and 1990s. Despite recent improvement in RCS levels, these data underscore the importance of continued medical surveillance of current and former surface coal miners.

ObjectivesSpirometry is the primary lung function test utilised for medical surveillance and disability examination for coal mine dust lung disease. However, spirometry likely underestimates physiologic impairment. We sought to characterise abnormalities of single-breath diffusing capacity for carbon monoxide (DLCO) among a population of former coal miners.MethodsData from 3115 former coal miners evaluated at a West Virginia black lung clinic between 2006 and 2015 were retrospectively analysed to study the association between diffusion impairment (abnormally low DLCO), resting spirometry and the presence and severity of coal workers’ pneumoconiosis on chest radiography. We developed ordinary least squares linear regression models to evaluate factors associated with per cent predicted DLCO (DLCOpp).ResultsDiffusion impairment was identified in 20.2% of subjects. Ten per cent of all miners with normal spirometry had diffusion impairment including 7.4% of never smokers. The prevalence of diffusion impairment increased with worsening radiographic category of pneumoconiosis. Mean DLCOpp decreased with increasing small opacity profusion subcategory in miners without progressive massive fibrosis. Linear regression analysis also showed significant decreases in DLCOpp with increasing small opacity profusion and presence of large opacities.ConclusionsDiffusion impairment is common among former coal miners, including among never smokers, miners without radiographic pneumoconiosis and miners with normal spirometry. These findings demonstrate the value of including DLCO testing in disability examinations of former coal miners and an important role for its use in medical surveillance of working miners to detect early chronic lung disease.

Military deployment to Southwest Asia and Afghanistan is linked to complex hazardous airborne exposures, but ascertaining the contributions of specific environmental toxicants in causing or contributing to deployment-related distal lung diseases (DDLD) remains challenging. We applied a quantitative microscopy for particulate matter (QM-PM) technique to measure the in situ burden of pigmented and birefringent lung particulates in 24 veterans with DDLD, 10 smokers with respiratory bronchiolitis (RB), and 10 healthy controls. Veterans were more likely to be male (88%) and were significantly younger than RB and healthy controls (mean age 41 vs. 47 vs. 53 years, respectively). Adjusting for age, the anthracotic pigment fraction in lung tissue from DDLD was similar to RB (1.69% vs. 1.37%, P  = 0.72), and was significantly greater than healthy controls (0.52%, P  = 0.02). Pigment fraction in veterans was significantly associated with higher reported burn pit smoke exposure ( P  = 0.02), but not sandstorms or diesel exhaust. Birefringent dust density, indicating retained silica/silicates, was significantly increased in RB (28.89/mm 2 , P  < 0.01) compared to DDLD and healthy control groups (8.93 and 9.44/mm 2 ). Findings suggest that lung deposition of anthracotic dust from burn pit smoke exposure in previously deployed post-9/11 military veterans may be important in the pathogenesis of DDLD.

There has been a resurgence of progressive massive fibrosis (PMF) in the United States, particularly among central Appalachian miners. We characterized the proportion of PMF among former U.S. coal miners applying for Federal Black Lung Program benefits, 1970-2016. Data from the U.S. Department of Labor were used to characterize trends in proportion of PMF cases, defined as an approved black lung claim with a determination of PMF, among all miners who filed for federal benefits between January 1, 1970, and December 31, 2016. Joinpoint, logistic, and linear regression models were used to identify changes in the proportion of claimants with PMF over time. There were 4,679 unique PMF cases among claimants for federal black lung benefits between 1970 and 2016, with 2,474 miners determined to have PMF since 1996. The number of PMF cases among Federal Black Lung Program claimants fell from 404 (0.5% of claimants) in 1978 to a low of 18 cases (0.6%) in 1988, and then increased to 353 cases (8.3%) in 2014. The proportion of federal black lung benefits claimants with PMF has been increasing since 1978 (0.06% annual percent change [APC]; 95% confidence interval [CI], 0.05-0.07%; P < 0.0001), and began increasing at a significantly increased rate after 1996 (0.26% APC; 95% CI, 0.25-0.28%; P < 0.0001). Most miners with PMF (84%) last mined in West Virginia, Kentucky, Pennsylvania, or Virginia. Since 1970, the proportion of claimants with PMF has increased significantly among miners who last worked in Kentucky (16.6% APC; 95% CI, 16.5-16.7%), Pennsylvania (4.7% APC; 95% CI, 4.6-4.8%), Tennessee (16.1% APC; 95% CI, 15.7-16.4%), West Virginia (16.8% APC; 95% CI, 16.6-16.9%), and most sharply among miners last working in Virginia (31.5% APC; 95% CI, 31.2-31.7%), where in 2009, more than 17% of claimants received a PMF determination. The proportion of PMF determinations for the rest of the United States has not exceeded 4%. There has been a resurgence of PMF, particularly in central Appalachian miners. The resurgence of this preventable disease points to the need for improved primary and secondary prevention of dust-related lung disease in U.S. coal miners.