Thin seams and small mines are associated with higher exposures to respirable crystalline silica in US underground coal mines.

OBJECTIVES: Previous 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. METHODS: We analysed RCS levels, as measured by respirable quartz, from coal mine dust compliance data from 1982 to 2021. RESULTS: We 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. CONCLUSIONS: These 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.

Measuring lung diffusing capacity: an opportunity for improved medical surveillance and disability evaluation of coal miners.

OBJECTIVES: Spirometry 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. METHODS: Data 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). RESULTS: Diffusion 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. CONCLUSIONS: Diffusion 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.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Poor adherence to dust, noise and safety regulations predict injury rates in underground coal mines.

BACKGROUND: While safety in US coal mining has improved over the past two decades, general occupational health research shows that risk of injury varies across individual worksites and is influenced by worksite safety cultures and practices. METHODS: In this longitudinal study, we evaluated whether mine-level characteristics reflecting poor adherence to health and safety regulations in underground coal mines are associated with higher acute injury rates. We aggregated Mine Safety and Health Administration (MSHA) data by year for each underground coal mine for the period 2000-2019. Data included part-50 injuries, mine characteristics, employment and production, dust sampling, noise sampling, and violations. Multivariable hierarchical generalised estimating equations (GEE) models were developed. RESULTS: Based on the final GEE model, despite an average annual decline in injury rates by 5.5%, the following indicators of inadequate adherence to health and safety regulations were associated with increased average annual injury rates: +2.9% for each 10% increase in dust samples exceeding the permissible exposure limit; +0.6% for each 10% increase of permitted 90 dBA 8-hour noise exposure dose; +2.0% for every 10 substantial-significant MSHA violations in a year; +1.8% for each rescue/recovery procedure violation; +2.6% for each safeguard violation. If a fatality occurred in a mine, injury rates increased by 11.9% in the same year, but declined by 10.4% in the following year. The presence of safety committees was associated with a 14.5% decline in injury rates. DISCUSSION: In US underground coal mines, injury rates are associated with poor adherence to dust, noise and safety regulations.

Increased odds of mortality from non-malignant respiratory disease and lung cancer are highest among US coal miners born after 1939.

OBJECTIVES: Coal miners suffer increased mortality from non-malignant respiratory diseases (NMRD), including pneumoconioses and chronic obstructive pulmonary disease, compared with the US population. We characterised mortality trends from NMRD, lung cancer and ischaemic heart disease (IHD) using data from the Federal Black Lung Program, National Coal Workers' Health Surveillance Program and the National Death Index. METHODS: We compared mortality ORs (MORs) for NMRD, lung cancer and IHD in former US coal miners to US white males. MORs were computed for the study period 1979-2017 by birth cohort (<1920, 1920-1929, 1930-1939, ≥1940), with a subanalysis restricted to Central Appalachia. RESULTS: The study population totalled 235 550 deceased miners, aged >45 years. Odds of death from NMRD and lung cancer across all miner birth cohorts averaged twice those of US males. In Central Appalachia, MORs significantly increased across birth cohorts. There was an eightfold increase in odds of death from NMRD among miners born after 1940 (MORBC≥1940 8.25; 95% CI 7.67 to 8.87). Miners with progressive massive fibrosis (PMF) were younger at death than those without PMF (74 vs 78 years; p<0.0001). We observed a pattern of reduced MORs from IHD in coal miners compared with national and regional counterparts. CONCLUSION: US coal miners have excess mortality from NMRD and lung cancer compared with total US and Appalachian populations. Mortality is highest in the most recent birth cohorts, perhaps reflecting increased rates of severe pneumoconiosis.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

Global Trends in Occupational Lung Disease.

Lung diseases caused by workplace exposure are too often mis- or underdiagnosed due in part to nonexistent or inadequate health surveillance programs for workers. Many of these diseases are indistinguishable from those that occur in the general population and are not recognized as being caused at least in part by occupational exposures. More than 10% of all lung diseases are estimated to result from workplace exposures. This study reviews recent estimates of the burden of the most important occupational lung diseases using data published by United Nations specialized agencies as well as the Global Burden of Disease studies. We focus on occupational chronic respiratory disease of which chronic obstructive lung disease and asthma are the most significant. Among occupational cancers, lung cancer is the most common, and is associated with more than 10 important workplace carcinogens. Classic occupational interstitial lung diseases such as asbestosis, silicosis, and coal workers' pneumoconiosis still comprise a substantial burden of disease in modern industrial societies, while other occupational causes of pulmonary fibrosis and granulomatous inflammation are frequently misclassified as idiopathic. Occupational respiratory infections gained prominence during the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, eclipsing influenza and tuberculosis and other less common workplace infectious agents. The most significant risks are workplace exposures to particulate matter, gases, and fumes as well as occupational carcinogens and asthmagens. We present data on the burden of disease measured by deaths attributable to occupational respiratory disease as well as disability-adjusted years of life lost. Where available, prevalence and incidence data are also presented. These diseases are unique in that they are theoretically 100% preventable if appropriate exposure controls and workplace medical surveillance are implemented. This remains a continuing challenge globally and requires steadfast commitment on the part of government, industry, organized labor, and the medical profession.

Coal mine dust lung disease in miners killed in the Upper Big Branch disaster: a review of lung pathology and contemporary respirable dust levels in underground US coal mines.

OBJECTIVES: In 2010, 29 coal miners died due to an explosion at the Upper Big Branch (UBB) mine in West Virginia, USA. Autopsy examinations of 24 individuals with evaluable lung tissue identified 17 considered to have coal workers' pneumoconiosis (CWP). The objectives of this study were to characterise histopathological findings of lung tissue from a sample of UBB fatalities and better understand the respirable dust concentrations experienced by these miners at UBB relative to other US coal mines. METHODS: Occupational pulmonary pathologists evaluated lung tissue specimens from UBB fatalities for the presence of features of pneumoconiosis. Respirable dust and quartz samples submitted for regulatory compliance from all US underground coal mines prior to the disaster were analysed. RESULTS: Families of seven UBB fatalities provided consent for the study. Histopathologic evidence of CWP was found in all seven cases. For the USA, central Appalachia and UBB, compliance dust samples showed the geometric mean for respirable dust was 0.468, 0.420 and 0.518 mg/m3, respectively, and respirable quartz concentrations were 0.030, 0.038 and 0.061 mg/m3. After adjusting for quartz concentrations, UBB exceeded the US permissible exposure limit (PEL) for respirable dust in 28% of samples. CONCLUSIONS: Although higher than average respirable dust and quartz levels were observed at UBB, over 200 US underground coal mines had higher dust concentrations than UBB and over 100 exceeded the PEL more frequently. Together with lung histopathological findings among UBB fatalities, these data suggest exposures leading to CWP in the USA are more prevalent than previously understood.

Prevalence and severity of abnormal lung function among US former coal miners with and without radiographic coal workers' pneumoconiosis.

OBJECTIVES: Examination of lung function abnormalities among coal miners has historically focused on actively working miners. This likely underestimates the true burden of chronic respiratory disease. The objective of this study was to characterise patterns and severity of lung function impairment among a population of former coal miners. METHODS: Cross-sectional data from 2568 former coal miners evaluated at eight US Black Lung clinics in a 12-month period were retrospectively analysed for patterns of prebronchodilator spirometric abnormality and severity of lung function impairment. Spirometry data from a subset of former miners with chest radiographs were analysed based on the presence and severity of coal workers' pneumoconiosis (CWP). RESULTS: Abnormal spirometry was identified in 56.6% of subjects. The age-standardised prevalence of airflow obstruction among miners aged ≥45 years was 18.9% overall and 12.2% among never smokers. Among 1624 subjects who underwent chest radiography, the prevalence and severity of abnormal spirometry increased with worsening radiographic category for pneumoconiosis. Of never-smoking former miners without radiographic CWP, 39.0% had abnormal spirometry; 25.1% had abnormally low forced expiratory volume in 1 s (FEV1), and 17.1% had moderate to severe FEV1 impairment. CONCLUSIONS: Abnormal spirometry is common among former coal miners. While ever-smoking former miners had higher rates of airflow obstruction, never-smoking former miners also demonstrated clinically significant airflow obstruction, including those without radiographic pneumoconiosis. These findings demonstrate the importance of recognising physiological as well as imaging manifestations of coal mine dust lung diseases in former miners.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To 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. METHODS: With 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. RESULTS: Among 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. CONCLUSIONS: Findings 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.

Current global perspectives on silicosis-Convergence of old and newly emergent hazards.

Silicosis not a disease of the past. It is an irreversible, fibrotic lung disease specifically caused by exposure to respirable crystalline silica (RCS) dust. Over 20,000 incident cases of silicosis were identified in 2017 and millions of workers continue to be exposed to RCS. Identified case numbers are however a substantial underestimation due to deficiencies in reporting systems and occupational respiratory health surveillance programmes in many countries. Insecure workers, immigrants and workers in small businesses are at particular risk of more intense RCS exposure. Much of the focus of research and prevention activities has been on the mining sector. Hazardous RCS exposure however occurs in a wide range of occupational setting which receive less attention, in particular the construction industry. Recent outbreaks of silicosis associated with the fabrication of domestic kitchen benchtops from high-silica content artificial stone have been particularly notable because of the young age of affected workers, short duration of RCS exposure and often rapid disease progression. Developments in nanotechnology and hydraulic fracking provide further examples of how rapid changes in technology and industrial processes require governments to maintain constant vigilance to identify and control potential sources of RCS exposure. Despite countries around the world dealing with similar issues related to RCS exposure, there is an absence of sustained global public health response including lack of consensus of an occupational exposure limit that would provide protection to workers. Although there are complex challenges, global elimination of silicosis must remain the goal.

Early radiographic pneumoconiosis is associated with impaired exercise gas exchange among coal miners with normal resting spirometry.

RATIONALE: We sought to determine if radiographic pneumoconiosis predicts abnormal gas exchange during exercise in coal mine workers with preserved resting lung function. METHODS: We analyzed data from former coal miners seen between 2006 and 2014 in a single clinic specializing in black lung evaluations. We limited the analysis to those with normal resting spirometry and an A-a gradient at peak exercise ≥10 mmHg. We used multivariable logistic regression to estimate predictors of A-a gradient widened to >150% of the reference value. We focused on chest radiographs consistent with pneumoconiosis, taking into account higher silica exposure mining activities and years underground, and adjusting for cigarette smoking, obesity, and coronary artery disease. RESULTS: Of 5507 miners, we analyzed data for 742 subjects with normal spirometry and all key clinical variables available, of whom 372 (50.1%) had radiographic evidence of pneumoconiosis. All but 21 had small opacity profusion of less than 2/1. The median A-a gradient at peak exercise was 108% of reference value (interquartile range, 81%-141%). In the multivariable analysis, radiographic pneumoconiosis was associated with increased odds of widened A-a gradient (odds ratio [OR], 2.47; 95% confidence interval [CI], 1.7-3.7). Limited to 660 subjects with normal diffusing capacity for carbon monoxide, the odds were similarly increased (OR, 3.20; 95% CI, 1.5-3.6). DISCUSSION: Among coal miners with preserved resting lung function, radiographic evidence of early pneumoconiosis more than doubled the odds of abnormal exercise physiology. Impairment in pneumoconiosis occurs in early disease and may only be evident on exercise testing.

Progression of coal workers' pneumoconiosis absent further exposure.

OBJECTIVES: The natural history of coal workers' pneumoconiosis (CWP) after cessation of exposure remains poorly understood. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: This 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.

Lung disease and coal mining: what pulmonologists need to know.

PURPOSE OF REVIEW: Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. RECENT FINDINGS: Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. SUMMARY: A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Characterizing Lung Particulates Using Quantitative Microscopy in Coal Miners With Severe Pneumoconiosis.

CONTEXT.­: Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. OBJECTIVE.­: To explore polarized light microscopy coupled with image-processing software, termed quantitative microscopy-particulate matter (QM-PM), as a tool to characterize in situ dust in lung tissue of US coal miners with progressive massive fibrosis. DESIGN.­: We developed a standardized protocol using microscopy images to characterize the in situ burden of birefringent crystalline silica/silicate particles (mineral density) and carbonaceous particles (pigment fraction). Mineral density and pigment fraction were compared with pathologists' qualitative assessments and SEM/EDS analyses. Particle features were compared between historical (born before 1930) and contemporary coal miners, who likely had different exposures following changes in mining technology. RESULTS.­: Lung tissue samples from 85 coal miners (62 historical and 23 contemporary) and 10 healthy controls were analyzed using QM-PM. Mineral density and pigment fraction measurements with QM-PM were comparable to consensus pathologists' scoring and SEM/EDS analyses. Contemporary miners had greater mineral density than historical miners (186 456 versus 63 727/mm3; P = .02) and controls (4542/mm3), consistent with higher amounts of silica/silicate dust. Contemporary and historical miners had similar particle sizes (median area, 1.00 versus 1.14 µm2; P = .46) and birefringence under polarized light (median grayscale brightness: 80.9 versus 87.6; P = .29). CONCLUSIONS.­: QM-PM reliably characterizes in situ silica/silicate and carbonaceous particles in a reproducible, automated, accessible, and time/cost/labor-efficient manner, and shows promise as a tool for understanding occupational lung pathology and targeting exposure controls.

Pathologic Findings in Severe Coal Workers' Pneumoconiosis in Contemporary US Coal Miners.

CONTEXT.­: 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. OBJECTIVE.­: To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. DESIGN.­: 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. RESULTS.­: 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. CONCLUSIONS.­: 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.

Mining Tenure and Job Duties Differ Among Contemporary and Historic Underground Coal Miners With Progressive Massive Fibrosis.

OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners ( n = 33) had significantly shorter mean total (30.4 years vs 37.1 years, P = 0.0006) and underground (28.8 years vs 35.8 years, P = 0.001) mining tenure compared with historic miners ( n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs 15.8%, P = 0.03) and contemporary miners (58.1% vs 15.2%, P < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention.

Proteasomal inhibition after injury prevents fibrosis by modulating TGF-ß(1) signalling.

BACKGROUND: The development of organ fibrosis after injury requires activation of transforming growth factor ß(1) 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-ß(1)-mediated transcription. METHODS: Bortezomib, 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. RESULTS: Bortezomib 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-ß(1)-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. CONCLUSIONS: Proteasomal 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.