Progressive Massive Fibrosis Research Articles

Integrating routine blood biomarkers and artificial intelligence for supporting diagnosis of silicosis in engineered stone workers.

Engineered stone silicosis (ESS), primarily caused by inhaling respirable crystalline silica, poses a significant occupational health risk globally. ESS has no effective treatment and presents a rapid progression from simple silicosis (SS) to progressive massive fibrosis (PMF), with respiratory failure and death. Despite the use of diagnostic methods like chest x-rays and high-resolution computed tomography, early detection of silicosis remains challenging. Since routine blood tests have shown promise in detecting inflammatory markers associated with the disease, this study aims to assess whether routine blood biomarkers, coupled with machine learning techniques, can effectively differentiate between healthy individuals, subjects with SS, and PMF. To this end, 107 men diagnosed with silicosis, ex-workers in the engineered stone (ES) sector, and 22 healthy male volunteers as controls not exposed to ES dust were recruited. Twenty-one primary biochemical markers derived from peripheral blood extraction were obtained retrospectively from clinical hospital records. Relief-F features selection technique was applied, and the resulting subset of 11 biomarkers was used to build five machine learning models, demonstrating high performance with sensitivities and specificities in the best case greater than 82% and 89%, respectively. The percentage of lymphocytes, the angiotensin-converting enzyme, and lactate dehydrogenase indexes were revealed, among others, as blood biomarkers with significant cumulative importance for the machine learning models. Our study reveals that these biomarkers could detect a chronic inflammatory status and potentially serve as a supportive tool for the diagnosis, monitoring, and early detection of the progression of silicosis.

In Situ Lung Dust Analysis by Automated Field Emission Scanning Electron Microscopy With Energy Dispersive X-ray Spectroscopy: A Method for Assessing Inorganic Particles in Lung Tissue From Coal Miners.

Overexposure to respirable coal mine dust can cause severe lung disease including progressive massive fibrosis (PMF). Field emission scanning electron microscopy with energy dispersive x-ray spectroscopy (FESEM-EDS) has been used for in situ lung dust particle analysis for evaluation of disease etiology. Automating such work can reduce time, costs, and user bias. To develop and test an automated FESEM-EDS method for in situ analysis of inorganic particles in coal miner lung tissue. We programmed an automated FESEM-EDS procedure to collect particle size and elemental data, using lung tissue from 10 underground coal miners with PMF and 4 control cases. A statistical clustering approach was used to establish classification criteria based on particle chemistry. Data were correlated to PMF/non-PMF areas of the tissue, using corresponding brightfield microscopy images. Results for each miner case were compared with a separate corresponding analysis of particles recovered following tissue digestion. In situ analysis of miner tissues showed higher particle number densities than controls and densities were generally higher in PMF than non-PMF areas. Particle counts were typically dominated by aluminum silicates with varying percentages of silica. Compared to digestion results for the miner tissues, in situ results indicated lower density of particles (number per tissue volume), larger size, and a lower ratio of silica to total silicates-probably due to frequent particle clustering in situ. Automated FESEM-EDS analysis of lung dust is feasible in situ and could be applied to a larger set of mineral dust-exposed lung tissues to investigate specific histologic features of PMF and other dust-related occupational diseases.

Women in Coal Mining-Radiographic Findings of Women Participants in the Coal Workers' Health Surveillance Program 1970-2022.

Objective: To describe the work experience and respiratory health of women coal miners in the United States using Coal Workers' Health Surveillance Program (CWHSP) data. Methods: Analysis included CWHSP participants with self-reported sex of female between January 1, 1970, and December 31, 2022, and examined radiographic surveillance, demographics, and job history. National Institute for Occupational Safety and Health-certified physicians classified chest radiographs. Results: Among 8,182 women participants, most worked <10 years and a majority reported working in non-dusty jobs. Among 3,392 with ≥1 year of coal mining tenure, 18 (0.5%) had evidence of pneumoconiosis, with no cases of progressive massive fibrosis. Conclusion: Women coal miners participating in the CWSHP had short mining careers and low pneumoconiosis prevalence. Few worked in the most dusty jobs, indicating limited exposure to coal mine dust. This underscores the need to explore women's roles in mining, and for improved gender-specific employment reporting. Such changes can enhance health and work conditions for women in male-dominated industries.

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

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation.

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.

Influence of Mesh Design and Surface Treatments on Particle Transport and Fate in a Vibration-Enhanced Flooded Bed Dust Scrubber

Respirable coal mine dust (RCMD) is one of the biggest occupational health hazards for underground coal miners. Dusty mining environments can cause long-term health problems, including pneumoconiosis and progressive massive fibrosis. The Mine Safety and Health Administration (MSHA) has recently revised regulations promoting enhanced dust mitigation technologies, which have sparked renewed interest in the development of dust mitigation technologies. The flooded bed dust scrubber (FBS) is one of the most widely used technologies; however, it is limited by technical challenges, the most notable being the potential to clog. Recent studies have shown that applying vibration to filter mesh can improve the overall efficiency of the scrubber and that the system can be readily integrated to existing continuous mining equipment using an energy harvesting approach. In this follow-up study, the impact of mesh design and surface modification on system efficiency was examined using different vibrating liquid-coated stainless-steel mesh panels in a laboratory-scale FBS. Based on the two-way interaction data from a multi-factor experimental design, the results show that the performance of the system can be optimized by using hydrophilic 20- or 30-layer filters and by excitation frequencies between 67 and 134 Hz. This laboratory study suggests that a 20-layer mesh screen with hydrophilic surface applications and optimized vibration parameters can perform similar to that of a 30-layer static mesh, which is typically used in industrial units.

Erasmus syndrome: A rare case report

Erasmus syndrome is a rare clinical entity in which systemic sclerosis develops following exposure to silica with or without development of silicosis. There are very few cases reported in literature from India. Here we report a case of Erasmus syndrome in a 52 years male who is a stone crusher by occupation for last 22 years presented with dry cough, low grade irregular fever, progressive shortness of breath, slowly progressive sclerodactyly and features suggestive of Raynaud’s phenomenon. Radiological evaluations revealed multiple subpleural and centrilobular nodules in bilateral upper, lower lobes and right middle lobe, conglomerated nodular opacities (progressive massive fibrosis- PMF). There was pleural thickening and calcification, bronchial dilatation and fibrosis, calcified right hilar and mediastinal lymphadenopathy. Serological markers like Anti Scl-70 antibody came out to be positive (3+) Based on clinical features diagnosis of systemic sclerosis was made. Based on exposure history and radiology silicosis was diagnosed. Association of silicosis and systemic sclerosis establishes the diagnosis of Erasmus syndrome. Treatment was started with Prednisone, cyclophosphamide and Nifedipine. Strict avoidance to cold and regular follow-up was advised.

Progressive Massive Fibrosis Identified at Federally Funded Black Lung Clinics in the US

This study of US Black Lung Clinics (established to treat coal miners) reports the prevalence of progressive massive fibrosis identified through June 2023.

Silicosis Among Immigrant Engineered Stone (Quartz) Countertop Fabrication Workers in California

Key Points Question What are the characteristics of patients in California with silicosis from occupational exposure to dust from engineered stone (quartz), a popular material that is high in silica content and that is used to fabricate countertops? Findings In this case series of 52 patients, the median age was 45 years at diagnosis, and nearly all were Latino immigrant men. Diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died. Meaning In California, silicosis associated with occupational exposure to dust from engineered stone primarily occurred among young Latino immigrant men; many patients presented with severe disease, and some cases were fatal.

Silicosis Complicated by Progressive Massive Fibrosis

Silicosis Complicated by Progressive Massive Fibrosis

Erasmus Syndrome: A Rare Case Report of Systemic Sclerosis with Silicosis and Progressive Massive Fibrosis

Erasmus Syndrome is a rare disorder that is characterized by the development of systemic sclerosis after significantly prolonged exposure to silica with or without silicosis. Systemic Sclerosis is a multisystem autoimmune disease with vascular changes, inflammation, and diffuse tissue fibrosis. We report a case of Erasmus syndrome in a 45-year-old male who worked in the marble industry. The patient presented with difficulty in breathing, skin tightening, joint pain, Raynaud’s phenomenon, microstomia, and progressive massive fibrosis. Keywords: Erasmus Syndrome, Systemic Sclerosis, Silicosis, Progressive Massive Fibrosis

Tetrandrine slows the radiographic progression of progressive massive fibrosis in pneumoconiosis: a retrospective cohort study

ObjectiveThis study aims to explore the clinical effect of Tetrandrine (Tet) on progressive massive fibrosis (PMF) of pneumoconiosis.MethodsThis retrospective study collected 344 pneumoconiosis patients with PMF, and 127 were eligible for the final analysis, including 57 patients in the Tet group and 70 patients in the control group. The progress of imaging and lung function were compared between the two groups.ResultsAfter 13 months (median) of treatment, the size of PMF was smaller in the Tet group than that in the control group (1526 vs. 2306, p=0.001), and the size was stable in the Tet group (1568 vs. 1526, p= 0.381), while progressed significantly in the control group (2055 vs. 2306, p=0.000). The small nodule profusion and emphysema were also milder than that in the control group (6.0 vs. 7.5, p=0.046 and 8.0 vs. 12, p=0.016 respectively). Pulmonary ventilation function parameters FVC and FEV1 improved in the Tet group (3222 vs. 3301, p=0.021; 2202 vs. 2259, p=0.025 respectively) and decreased in the control group (3272 vs. 3185, p= 0.00; 2094 vs. 1981, p=0.00 respectively). FEV1/FVC was also significantly higher in the Tet group than that in the control group (68.45vs. 60.74, p=0.001). However, similar result was failed to observed for DLco%, which showed a significant decrease in both groups.ConclusionTet has shown great potential in the treatment of PMF by slowing the progression of pulmonary fibrosis and the decline of lung function.

Silicosis Among Immigrant Engineered Stone (Quartz) Countertop Fabrication Workers in California

Silicosis associated with inhalation of respirable crystalline silica among engineered stone countertop fabrication workers is an emerging health concern. To describe clinical, socioeconomic, and occupational characteristics of patients diagnosed with silicosis associated with engineered stone in California. This case series included reported cases of silicosis associated with fabrication of engineered stone countertops, as identified by statewide surveillance by the California Department of Public Health (2019-2022). Data analysis was performed from October 2022 to March 2023. Patient interviews and medical record abstractions were used to assess occupational exposure to respirable crystalline silica, including duration of work tenure and preventive measures undertaken. Demographics, clinical characteristics, health care utilization, and clinical outcomes were obtained, including vital status, hypoxia, and lung transplant. This case series identified 52 male patients meeting inclusion criteria; median (IQR) age was 45 (40-49) years, and 51 were Latino immigrants. Ten (19%) were uninsured, and 20 (39%) had restricted-scope Medi-Cal; 25 (48%) presented initially to an emergency department. A delay in diagnosis occurred in 30 (58%) patients, most commonly due to alternative initial diagnoses of bacterial pneumonia (9 [30%]) or tuberculosis (8 [27%]). At diagnosis, 20 (38%) patients had advanced disease (progressive massive fibrosis) with severely or very severely reduced forced expiratory volume in 1 second in 8 (18%) and 5 (11%), respectively. Of the cases, 10 (19%) were fatal; median (IQR) age at death was 46 (38-51) years, and 6 patients (12%) were alive with chronic resting hypoxia. Eleven were referred for lung transplant: 3 underwent transplant with 1 fatality; 7 were declined transplant, with 6 fatalities; and 1 died prior to listing. Median (IQR) work tenure was 15 (10-20) years; 23 (45%) reported use of water suppression for dust mitigation, and 25 (48%) continued to fabricate stone after being diagnosed with silicosis. In this case series performed in California, silicosis associated with occupational exposure to dust from engineered stone primarily occurred among young Latino immigrant men. Many patients presented with severe disease, and some cases were fatal.

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

BackgroundPneumoconiosis 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...

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

Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. 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. 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. 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). 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.

The dependence of particle size on cell toxicity for modern mining dust

Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180–3000 nm) compared to rock (495–2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p < 0.05). Fine particle fraction, approximately 200 nm for coal and 500 nm for rock particles, explicitly induced stronger inflammatory reactions than their coarser counterparts. Future work will study additional toxicity endpoints to further elucidate the molecular mechanism causing pulmonary toxicity and determine a dose–response curve.

Plasma Cytokine Profiling Reveals Differences between Silicotic Patients with Simple Silicosis and Those with Progressive Massive Fibrosis Caused by Engineered Stone.

Engineered stone silicosis has become an occupational epidemic disease that progresses rapidly to progressive massive fibrosis with respiratory failure and death, and there is no effective treatment. Silica deposition in the lung triggers a series of inflammatory reactions with the participation of multiple cytokines and cellular mediators whose role in the development and progression of the disease is largely unknown. We hypothesized that differences in plasma cytokine levels exist between patients diagnosed with simple silicosis (SS) and patients diagnosed with progressive massive fibrosis (PMF). Plasma samples from 91 ES silicosis patients, diagnosed and classified by chest radiography and/or high-resolution computed tomography with SS (n = 53) and PMF (n = 38), were assayed by multiplex assays for levels of 34 cytokines. Additionally, a healthy volunteer control group (n = 22) was included. Plasma levels of a high number of cytokines were significantly higher in subjects with silicosis than in healthy control subjects. Moreover, the levels of IL-1RA, IL-8, IL-10, IL-16, IL-18, TNF-α, MIP-1α, G-CSF and VEGF were significantly elevated in PMF compared to SS patients. This study shows that plasma cytokine levels differ between healthy people and silicosis patients, and some of them are also significantly elevated in patients with PMF compared with patients with SS, which could indicate their involvement in the severity of the disease, be considered as biomarkers and could be explored as future therapeutic targets for the disease.

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

ObjectivesCoal 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...

A Case of Lung Cancer Developing in the Background of Progressive Massive Fibrosis

A Case of Lung Cancer Developing in the Background of Progressive Massive Fibrosis

Lipid dysregulation associated with progression of silica-induced pulmonary fibrosis.

Silicosis is an irreversible, progressive, fibrotic lung disease caused by long-term exposure to dust-containing silica particles at the workplace. Despite the precautions enforced, the rising incidence of silicosis continues to occur globally, particularly in developing countries. A better understanding of the disease progression and potential metabolic reprogramming of silicosis is warranted. The low- or high-dose silica-induced pulmonary fibrosis in mice was constructed to mimic chronic or accelerated silicosis. Silica-induced mice lung fibrosis was analyzed by histology, lung function, and computed tomography scans. Non-targeted metabolomics of the lung tissues was conducted by ultra-high-performance liquid chromatography-mass spectrometry to show the temporal metabolic trajectory. The low-dose silica-induced silicosis characterized inflammation for up to 42 days, with the onset of cellular silicon nodules. Conversely, the high-dose silica-induced silicosis characterized inflammation for up to 14 days, after which the disease developed rapidly, with a large volume of collagen deposition, presenting progressive massive fibrosis. Both low- and high silica-induced fibrosis had aberrant lipid metabolism. Combined with the RNA-Seq data, this multiomics study demonstrated alterations in the enzymes involved in sphingolipid metabolism. Time-dependent metabolic reprogramming revealing abnormal glycerophospholipid metabolism was intimately associated with the process of inflammation, whereas sphingolipid metabolism was crucial during lung fibrosis. These findings suggest that lipid dysregulation, especially sphingolipid metabolism, was involved in the process of silicosis.