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.

Vitamin D3 reverses immune tolerance and enhances the cytotoxicity of effector T cells in coal pneumoconiosis.

Coal worker's pneumoconiosis (CWP) is a common occupational disease that coal miners are highly susceptible due to long-term exposure to coal dust particles (CDP). CWP can induce the accumulation of immune cells surrounding the bronchioles and alveoli in the lungs, resulting in pulmonary fibrosis and compromised immune function. Using single-cell RNA sequencing (scRNA-Seq), our previous studies disclose that CDP exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis, while Vitamin D3 (VitD3) supplementation reduces CDP-induced cytotoxicity; however, the mechanism by which how VitD3 regulates immune status in coal pneumoconiosis remains unclear. In this study, we elucidated the heterogeneity of pulmonary lymphocytes in mice exposed to CDP and demonstrated the therapeutic efficacy of VitD3 using scRNA-Seq dataset. The validation of key lymphocyte markers and their functional molecules was performed using immunofluorescence. The results demonstrated that VitD3 increased the number of naive T cells by modulating CD4 + T cell differentiation and decreased the number of Treg cells in CDP-exposed mice, thereby enhancing the cytotoxic activity of CD8 + effector T cells. These effects markedly alleviated lung fibrosis and symptoms. Taken together, the mechanism by which VitD3 regulates the functions of lymphocytes in CWP provides a new perspective for further research on the prevention and treatment of CWP.

[Changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis].

Objective: To observe the changes of lung function and inflammatory factors in rat models of coal workers' pneumoconiosis at different time points. Methods: In June 2021, 96 healthy male SD rats with SPF grade were divided into 1, 3, and 6-month control group and dust staining group (coal dust group, coal silica dust group, quartz group) according to random number table method, with 8 rats in each group. After one week of adaptive feeding, a one-time non-exposed tracheal perfusion method (1 ml/ piece) was used. The dust dyeing group was given 50 g/L coal dust, coal silica mixed dust and quartz dust suspension, respectively, and the control group was given 0.9% normal saline solution. At 1, 3 and 6 months after perfusion, lung function was detected by animal lung function apparatus, then all lung tissues and alveolar lavage fluid were killed, and lung histopathological morphological changes were observed by HE staining, and the contents of interleukin (IL-1ß), IL-18, IL-4 and IL-10 in alveolar lavage fluid were detected by ELISA. One-way analysis of variance was used to compare groups. Two factors (inter-group treatment factor (4 levels) and observation time factor (3 levels) ) were used in the analysis of the effects of inter-group treatment and treatment time on related indicators. Results: HE staining results showed that coal spot appeared in the lung tissue of coal dust group, coal spot and coal silicon nodule appeared in the lung tissue of coal dust group, and silicon nodule appeared in the lung tissue of quartz group. Compared with the control group, the forced vital capacity (FVC) and forced expiratory volume at 0.2 second (FEV(0.2)) of rats in the dust staining group had interaction between the treatment and treatment time (P<0.05). With the increase of dust dyeing time, FVC and FEV(0.2) decreased significantly at 3-6 months of dust dyeing, and the maximum gas volume per minute (MVV) decreased significantly at 1-3 months of dust dyeing (P<0.05). The lowest lung function index was in quartz group, followed by coal-silica group and coal-dust group. There were statistically significant differences in the main effect and interaction effect of the pro-inflammatory factor IL-18 among all groups in treatment and treatment time (IL-18: F=70.79, 45.97, 5.90, P<0.001), and interaction existed. The highest content of inflammatory factors in alveolar lavage fluid of all dust groups was quartz group, followed by coal silica group and coal dust group. There were significant differences in the main effect and interaction effect of anti-inflammatory factors between groups and treatment time (IL-4: F=41.55, 33.01, 5.23, P<0.001, <0.001, <0.001; IL-10: F=7.46, 20.80, 2.91, P=0.002, <0.001, 0.024), and there was interaction. The highest content of anti-inflammatory factor was in quartz group, followed by coal silica group and coal dust group. Conclusion: Lung function decreased and levels of inflammatory fators increased in rat models of coal workers' pneumoconiosis, with the quartz group being the most severely damaged. Lung function is mainly impaired in thrid-six months, and the content of inflammatory factors begins to change in first-thrid months. MVV are the earliest and most obvious in lung function. IL-18 is suitable for monitoring changes in the pro-inflammatory response of coal workers' pneumoconiosis, and IL-10 is suitable for monitoring changes in anti-inflammatory response.

[Study on the risk factors of coal workers' pneumoconiosis and the mechanism of pyroptosis in peripheral blood].

Objective: To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease. Methods: From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1ß and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis. Results: All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age (F=4.95, P=0.003) and lunch break distribution (H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups (P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups (P<0.05). The levels of IL-18 and IL-1ß in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups (P<0.05). Multiple logistic regression analysis showed that smoking age (OR=1.03, 95%CI: 1.00-1.06) and IL-1ß level (OR=4.61, 95%CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis (P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased (P<0.05) . Conclusion: Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1ß may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

A nested case-control study of the effects of dust exposure, smoking on COPD in coal workers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction. METHOD: A nested case-control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017-2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers. RESULTS: The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers. CONCLUSION: Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.

Genetic susceptibility in pneumoconiosis in China: a systematic review.

OBJECTIVE: Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies revealed significant associations between genetic variations and pneumoconiosis risk among individuals in different countries. With the known variability of genetic makeup between ethnicities, susceptibility to pneumoconiosis due to genetic differences is likely to be ethnicity-specific. The present review aimed at providing a comprehensive overview on the association between genetic polymorphisms and susceptibility of pneumoconiosis, specifically among people in China. METHODS: The literature search was performed in seven English and Chinese databases using keywords related to the review aim. An appraisal of the methodological quality of the included studies was conducted using the assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. RESULTS: Forty-five studies were included in this review. Genotypes of specific genes which are associated with the risk of CWP, silicosis and asbestosis were reported. Our findings showed that genes encoding inflammatory cytokines have been examined extensively, and they demonstrated an association between these genes and pneumoconiosis risk. Gene-environment interactions in pneumoconiosis susceptibility were also reported by a number of studies. CONCLUSIONS: This review summarised the evidence demonstrating the association between genetic polymorphisms and pneumoconiosis susceptibility among people in China, and that various genotypes could modify their risk to develop pneumoconiosis. The findings prompt that identification of individuals at high pneumoconiosis risk through genetic screening and strategies limiting their exposure to dust could be a potential strategy for the control of this occupational disease in China.

Pneumoconiosis incidence and prevalence among US Medicare beneficiaries, 1999-2019.

BACKGROUND: Pneumoconiosis is a group of occupational lung diseases caused by dust and fiber exposure. This study analyzes Medicare claims to estimate the burden of pneumoconiosis among fee-for-service (FFS; Medicare Parts A and B) Medicare beneficiaries during 1999-2019 in the United States. METHODS: Claim and enrollment information from 81 million continuously enrolled FFS Medicare beneficiaries were analyzed. Beneficiaries with any pneumoconiosis and cause-specific pneumoconiosis (e.g., asbestosis, silicosis) were identified using three case definitions (broad, intermediate, and narrow) with varying diagnostic criteria based on claim International Classification of Diseases, Clinical Modification (ICD-CM) diagnosis codes and Healthcare Common Procedure Coding System codes. Results are presented as ranges of values for the three case definitions. RESULTS: The 21-year prevalence range for any pneumoconiosis was 345,383-677,361 (412-833 per 100,000 beneficiaries) using the three case definitions. The highest prevalence was among those ≥75 years of age, males, Whites, and North American Natives. Most claims (70.0%-72.5%) included an ICD-CM diagnosis code for asbestosis. The broad pneumoconiosis prevalence rate increased significantly (p < 0.001) during 2002-2009 by 3%-10% annually and declined significantly by 3%-5% annually starting in 2009. The average annual broad incidence rate declined significantly by 7% annually during 2009-2019. CONCLUSIONS: Despite the decline in rate for any pneumoconiosis among Medicare beneficiaries, which is primarily attributed to a decline in asbestosis, pneumoconiosis is prevalent among FFS Medicare beneficiaries.

Exosomal miRNAs contribute to coal dust particle-induced pulmonary fibrosis in rats.

Coal workers' pneumoconiosis (CWP) is a fatal occupational disease caused by inhalation of coal dust particles, which leads to progressive pulmonary fibrosis. Recently, as new signal carriers for intercellular communication, exosomal miRNAs have been validated in the pathogenesis of multiple diseases. However, the research on exosomal miRNAs in CWP is still in the preliminary stage. Here, using miRNA sequencing, exosomal miRNA profiles in bronchoalveolar lavage fluid (BALF) from rats with pulmonary fibrosis induced by coal dust particles were analyzed, and the underlying biological function of putative target genes was explored by GO term analysis and KEGG pathway enrichment analysis. According to the results, intratracheal instillation of coal dust particles can alter the exosomal miRNAs expression in the BALF of rats. Further bioinformatics analysis provided some clues to reveal their function in pathological process of pneumoconiosis. More importantly, we identified 4 differentially expressed exosomal miRNAs (miRNA-21-5p, miRNA-29a-3p, miRNA-26a-5p, and miRNA-34a-5p) by qRT­PCR and further verified the temporal changes in the expression of these exosomal miRNAs in animal models from 2 weeks to 16 weeks postexposure. In addition, we conducted a preliminary study on Smad7 as a potential target of miRNA-21-5p and found that exosomal miRNA 21-5p/Smad7 may contribute to the pulmonary fibrosis induced by coal dust particles. Our study confirmed the contribution of exosomal miRNAs to coal dust particle-induced pulmonary fibrosis and provided new insights into the pathogenesis of CWP.

Differential expression profile of microRNAs in the lung tissues of coal workers with pneumoconiosis and patients with silicosis.

The purpose of this study was to characterize the microRNA (miRNA) profile of the lung tissues from coal workers' pneumoconiosis (CWP) and silicosis and to analyze the changes in downstream genes, biological processes, and signaling pathways based on the differently expressed miRNAs. Lung tissues from three CWP patients, eight silicosis patients, and four healthy controls were collected and analyzed for their miRNA profiles using Affymetrix® GeneChip® miRNA Arrays. Differentially expressed miRNAs (DEMs) were identified between the different groups. The miRanda and TargetScan databases were used to predict the putative target genes, and volcano and heat maps were drawn. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were then performed to screen the DEMs-associated biological process and signaling pathways, respectively. Further identification with a comprehensive literature research involving particle exposure, fibrosis, inflammation and lung cancer were used to further screen DEMs of CWP and silicosis. Microarray data showed that 375 and 88 miRNAs were differentially expressed in CWP and silicosis lung tissues compared with healthy lung tissues, while 34 miRNAs were differentially expressed in CWP compared with silicosis lung tissues. The GO and KEGG pathway analyses showed that, the target genes were mainly enriched in the TGF-ß, MAPK, p53 and other signal pathways. These results provided insight into the miRNA-related underlying mechanisms of CWP and silicosis, and they provided new clues for miRNAs as biomarkers for the diagnosis and differential diagnosis of these two diseases.

The impact of coal mine dust characteristics on pathways to respiratory harm: investigating the pneumoconiotic potency of coals.

Exposure to dust from the mining environment has historically resulted in epidemic levels of mortality and morbidity from pneumoconiotic diseases such as silicosis, coal workers' pneumoconiosis (CWP), and asbestosis. Studies have shown that CWP remains a critical issue at collieries across the globe, with some countries facing resurgent patterns of the disease and additional pathologies from long-term exposure. Compliance measures to reduce dust exposure rely primarily on the assumption that all "fine" particles are equally toxic irrespective of source or chemical composition. For several ore types, but more specifically coal, such an assumption is not practical due to the complex and highly variable nature of the material. Additionally, several studies have identified possible mechanisms of pathogenesis from the minerals and deleterious metals in coal. The purpose of this review was to provide a reassessment of the perspectives and strategies used to evaluate the pneumoconiotic potency of coal mine dust. Emphasis is on the physicochemical characteristics of coal mine dust such as mineralogy/mineral chemistry, particle shape, size, specific surface area, and free surface area-all of which have been highlighted as contributing factors to the expression of pro-inflammatory responses in the lung. The review also highlights the potential opportunity for more holistic risk characterisation strategies for coal mine dust, which consider the mineralogical and physicochemical aspects of the dust as variables relevant to the current proposed mechanisms for CWP pathogenesis.

[Application of a light-weighted convolutional neural network for automatic recognition of coal workers' pneumoconiosis in the early stage].

Objective: To construct and verify a light-weighted convolutional neural network (CNN), and explore its application value for screening the early stage (subcategory 0/1 and stage Ⅰ of pneumoconiosis) of coal workers' pneumoconiosis (CWP) from digital chest radiography (DR) . Methods: A total of 1225 DR images of coal workers who were examined at an Occupational Disease Prevention and Control Institute in Anhui Province from October 2018 to March 2021 were retrospectively collected. All DR images were collectively diagnosed by 3 radiologists with diagnostic qualifications and gave diagnostic results. There were 692 DR images with small opacity profusion 0/- or 0/0 and 533 DR images with small opacity profusion 0/1 to stage Ⅲ of pneumoconiosis. The original chest radiographs were preprocessed differently to generate four datasets, namely 16-bit grayscale original image set (Origin16), 8-bit grayscale original image set (Origin 8), 16-bit grayscale histogram equalized image set (HE16) and 8-bit grayscale histogram equalized image set (HE8). The light-weighted CNN, ShuffleNet, was applied to train the generated prediction model on the four datasets separately. The performance of the four models for pneumoconiosis prediction was evaluated on a test set containing 130 DR images using measures such as the receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, and Youden index. The Kappa consistency test was used to compare the agreement between the model predictions and the physician diagnosed pneumoconiosis results. Results: Origin16 model achieved the highest ROC area under the curve (AUC=0.958), accuracy (92.3%), specificity (92.9%), and Youden index (0.8452) for predicting pneumoconiosis, with a sensitivity of 91.7%. And the highest consistency between identification and physician diagnosis was observed for Origin16 model (Kappa value was 0.845, 95%CI: 0.753-0.937, P<0.001). HE16 model had the highest sensitivity (98.3%) . Conclusion: The light-weighted CNN ShuffleNet model can efficiently identify the early stages of CWP, and its application in the early screening of CWP can effectively improve physicians' work efficiency.

Effects of chemical composition on the lung cell response to coal particles: Implications for coal workers' pneumoconiosis.

BACKGROUND AND OBJECTIVE: Coal mine dust has a complex and heterogeneous chemical composition. It has been suggested that coal particle chemistry plays a critical role in determining the pathogenesis of coal workers' pneumoconiosis (CWP). In this study, we aimed to establish the association between the detrimental cellular response and the chemical composition of coal particles. METHODS: We sourced 19 real-world coal samples. Samples were crushed prior to use to minimize the impact of particle size on the response and to ensure the particles were respirable. Key chemical components and inorganic compounds were quantified in the coal samples. The cytotoxic, inflammatory and pro-fibrotic responses in epithelial cells, macrophages and fibroblasts were assessed following 24 h of exposure to coal particles. Principal component analysis (PCA) and stepwise regression were used to determine which chemical components of the coal particles were associated with the cell response. RESULTS: The cytotoxic, inflammatory and pro-fibrotic response varied considerably between coal samples. There was a high level of collinearity in the cell responses and between the chemical compounds within the coal samples. PCA identified three factors that explained 75% of the variance in the cell response. Stepwise multiple regression analysis identified K2 O (p <0.001) and Fe2 O3 (p = 0.011) as significant predictors of cytotoxicity and cytokine production, respectively. CONCLUSION: Our data clearly demonstrate that the detrimental cellular effects of exposure to coal mine dusts are highly dependent on particle chemistry. This has implications for understanding the pathogenesis of CWP.

Use data augmentation for a deep learning classification model with chest X-ray clinical imaging featuring coal workers' pneumoconiosis.

PURPOSE: This paper aims to develop a successful deep learning model with data augmentation technique to discover the clinical uniqueness of chest X-ray imaging features of coal workers' pneumoconiosis (CWP). PATIENTS AND METHODS: We enrolled 149 CWP patients and 68 dust-exposure workers for a prospective cohort observational study between August 2021 and December 2021 at First Hospital of Shanxi Medical University. Two hundred seventeen chest X-ray images were collected for this study, obtaining reliable diagnostic results through the radiologists' team, and confirming clinical imaging features. We segmented regions of interest with diagnosis reports, then classified them into three categories. To identify these clinical features, we developed a deep learning model (ShuffleNet V2-ECA Net) with data augmentation through performances of different deep learning models by assessment with Receiver Operation Characteristics (ROC) curve and area under the curve (AUC), accuracy (ACC), and Loss curves. RESULTS: We selected the ShuffleNet V2-ECA Net as the optimal model. The average AUC of this model was 0.98, and all classifications of clinical imaging features had an AUC above 0.95. CONCLUSION: We performed a study on a small dataset to classify the chest X-ray clinical imaging features of pneumoconiosis using a deep learning technique. A deep learning model of ShuffleNet V2 and ECA-Net was successfully constructed using data augmentation, which achieved an average accuracy of 98%. This method uncovered the uniqueness of the chest X-ray imaging features of CWP, thus supplying additional reference material for clinical application.

Cost-effectiveness of comprehensive preventive measures for coal workers' pneumoconiosis in China.

BACKGROUND: Coal workers' pneumoconiosis (CWP) remains one of the most severe occupational diseases in China. Despite the implementation of CWP comprehensive preventive measures, the unreasonable allocation of investment by coal enterprises limits the effect of preventing CWP, especially when the health resources are inadequate. This study aims to evaluate the cost-effectiveness of comprehensive measures for CWP from the perspective of coal enterprises. METHODS: Comprehensive measures and two primary interventions (engineering controls and individual protective equipment) were selected. A time-dependent Markov model was developed to evaluate cost and quality-adjusted life-years (QALYs). The input data were collected from the survey and literature. A hypothetical null situation, in which the currently implemented interventions were eliminated, was used as a comparator based on the generalised cost-effectiveness analysis (GCEA) recommended by the World Health Organization (WHO). The primary outcomes of the model were reported in terms of incremental cost-effectiveness ratios (ICERs). Uncertainty was verified using one-way and probabilistic sensitivity analyses. RESULTS: The QALYs of the comprehensive measures, engineering controls, and individual protective equipment were 17.60, 17.50, and 16.85 years, respectively. Compared with null, the ICERs of the interventions were 65,044.73, 30,865.15, and 86,952.41 RMB/QALY, respectively. Individual protective equipment was dominated by an ICER of -11,416.02 RMB/QALY compared to engineering controls. Sensitivity analysis suggested the robustness of the results. CONCLUSIONS: The comprehensive preventive measures for CWP that are currently implemented in Chinese state-owned mines are cost-effective. In comprehensive measures, engineering controls are more cost-effective than individual protective equipment. Investment in engineering controls should be increased to improve the cost-effectiveness of preventing CWP.

Glycogen metabolism reprogramming promotes inflammation in coal dust-exposed lung.

Long-term coal dust exposure triggers complex inflammatory processes in the coal workers' pneumoconiosis (CWP) lungs. The progress of the inflammation is reported to be affected by disordered cell metabolism. However, the changes in the metabolic reprogramming associated with the pulmonary inflammation induced by the coal dust particles are unknown. Herein, we show that coal dust exposure causes glycogen accumulation and the reprogramming of glucose metabolism in the CWP lung. The glycogen accumulation caused by coal dust is mainly due to macrophages, which reprogram glycogen metabolism and trigger an inflammatory response. In addition, 2-deoxy-D-glucose (2-DG) reduced glycogen content in macrophages, which was accompanied by mitigated inflammation and restrained NF-κB activation. Accordingly, we have pinpointed a novel and crucial metabolic pathway that is an essential regulator of the inflammatory phenotype of coal dust-exposed macrophages. These results shed light on new ways to regulate CWP inflammation.

Transcriptome-wide association study identifies PSMB9 as a susceptibility gene for coal workers' pneumoconiosis.

Coal workers' pneumoconiosis (CWP) is a type of typical occupational lung disease caused by prolonged inhalation of coal mine dust. The individuals' different genetic background may underlie their different susceptibility to develop pneumoconiosis, even under the same exposure level. This study aimed to identify susceptibility genes associated with CWP. Based on our previous genome-wide association study (GWAS, 202 CWP cases vs. 198 controls) and gene expression data obtained by analyzing human lungs and whole blood from the Genotype-Tissue Expression (GTEx) Portal, a transcriptome-wide association study (TWAS) was applied to identify CWP risk-related genes. Luciferase report gene assay, qRT-PCR, Western blot, immunofluorescence assay, and TUNEL assay were conducted to explore the potential role of the candidate gene in CWP. Proteasome 20S subunit beta 9 (PSMB9) was identified as a strong risk-related gene of CWP in both lungs and whole blood (Lungs: PTWAS  = 4.22 × 10-4 ; Whole blood: PTWAS  = 2.11 × 10-4 ). Single nucleotide polymorphisms (SNPs) rs2071480 and rs1351383, which locate in the promoter region and the first intron of the PSMB9 gene, were in high linkage disequilibrium (LD, r2  = 0.98) with the best GWAS SNP rs4713600 (G>T, OR = 0.55, 95% CI: 0.42-0.74, P = 6.86 × 10-5 ). Both rs2071480 and rs1351383 significantly enhanced the transcriptional activity of PSMB9. Functional experiments revealed that silica exposure remarkably reduced the PSMB9 expression and caused cell apoptosis, while overexpression of PSMB9 markedly abolished silica-induced cell apoptosis. We here identified PSMB9 as a novel susceptibility gene for CWP and provided important insights into the further exploration of the CWP pathogenesis.

[Expression and functional SNP loci screen of ATM from coal worker's pneumoconiosis].

Objective: To detect of gene expression and genotype of the ataxia telangiectasia mutated (ATM) from coal workers' pneumoconiosis (CWP) , It is explored whether CWP is related to ATM gene. Methods: In October 2020, the relevant information of 264 subjects who received physical examination or medical treatment in the Department of occupational diseases of Guiyang public health treatment center from January 2019 to September 2020 was collected. Through the occupational health examination, 67 healthy people with no history of exposure to occupational hazards were selected as the healthy control group; The coal miners with more than 10 years of coal dust exposure history and small shadow in the lung but not up to the diagnostic criteria were the dust exposure control group, a total of 66 people; The patients with the same history of coal dust exposure and confirmed stage I were coal worker's pneumoconiosis stage I group, a total of 131 people. The expression of ATM was detected by QRT PCR. ATM rs189037 and rs1801516 were genotyped by massarray. Results: There was significant difference in the expression of ATM among the groups (P<0.05) ; Compared with the healthy control group, the expression of ATM in the dust exposed control group was significantly increased (P<0.05) . With the occurrence and development of CWP, the GG of rs189037 wild type decreased, the GA of mutant heterozygote and AA of homozygote increased, but the difference was not statistically significant (P>0.05) ; Rs1801516 wild type GG and mutant heterozygote GA had no significant changes (P>0.05) . There were significant differences in age, neutrophils and basophils among rs189037 groups (all P<0.05) . There were no significant differences in blood pressure, eosinophils, lymphocytes, monocytes, smoking and drinking history among rs189037 groups (all P>0.05) . Compared with wild-type GG, the or of mutant heterozygotes and homozygotes increased, but the differences were not statistically significant (P>0.05) . Conclusion: ATM gene may be one of the early activation genes of CWP and rs189037 may be the functional loci which affects gene expression. ATM gene is related to inflammatory response, Neutrophils and basophils have an impact on the development of CWP.

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.

The impacts of coal dust on miners' health: A review.

As one of the most important energy resources in the world, coal contributes a great deal to the world economy. Coal mining and processing involve multiple dust generation processes including coal cutting, transport, crushing and milling etc. Coal dust is one of the main sources of health hazard for the coal workers. Exposure of coal dusts can be prevented through administrative controls and engineering controls. Ineffective control of coal dust exposure can harm coal workers' health. Although many efforts have been made to eliminate these threats, recent years have seen an unexpected increase in coal workers' pneumoconiosis (CWP) in Appalachian basin in US. To explore the reasons for this phenomenon, in this review, we first reviewed the historical studies on coal mine dust including the regulation and engineering controls. Then, the effects of coal dust on human health was comprehensively reviewed. Next, the effects of nanoparticles on human health were reviewed, with an emphasis on toxicity of nanoparticles such as carbon nanotubes in other industries. From all this information, we hypothesize that nano-sized coal dust has contributed to the increase of CWP prevalence in recent years. As no research has been reported in this area, four directions which may need further investigation and future studies are recommended in this review. They include: 1) Systematic characterization of physicochemical properties of nano-size coal dust; 2) Toxicity and pathogenesis of nano-sized coal dust; 3) Development of real-time monitoring technology and equipment for nano-sized coal dust; 4) Development of exposure control technology and equipment. The intent of this review paper is to demonstrate the variation of coal dust properties and their impact on the mine worker's health. We suggest that the impact of nano-sized coal mine dust on miner's health has not yet been understood well and further improvements are necessary.