Occupational Silica Research Articles

Exosomal proteomics and cytokine analysis distinguish silicosis cases from controls

Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.

Occupational exposures and sarcoidosis: a rapid review of the evidence.

Sarcoidosis is a rare, multisystem, inflammatory condition associated with the formation of granulomas. Diagnosis can be challenging because of non-specific symptoms complicating epidemiological investigations of its aetiology. Despite research efforts, a review of the current state of the evidence is needed. To assess the evidence for an association between occupational exposures and the development of sarcoidosis. To determine if workers in any occupation are at a greater risk of developing sarcoidosis. This rapid review follows the methodology suggested by the World Health Organization. Two electronic databases were systematically searched until April 2022. The methodological quality of the studies was critically appraised, and a best-evidence approach was used to synthesize the results. Titles and abstracts of 2916 articles were screened, with 67 full-text articles reviewed for eligibility. Among the 13 studies eligible for this review, none were of high quality (i.e. low risk of bias). Six studies exploring the association between sarcoidosis and a range of occupations and exposures, and one previous systematic review were of low quality reporting inconsistent findings. Six studies examined the risk of sarcoidosis associated with occupational silica exposure, two of which were of acceptable quality. Overall, the study methodologies and results were inadequate to support causal relationships. There is limited evidence of acceptable methodological quality to assess the risk of sarcoidosis associated with occupational exposures. There is a growing body of research examining occupational exposure to silica and sarcoidosis. Additional high-quality confirmatory research is needed.

Systemic sclerosis, silica exposure and cellular therapies: The sand in the gears?

Systemic sclerosis (SSc) is a chronic orphan autoimmune disease with the highest mortality rate among rheumatic diseases. SSc-related interstitial-lung disease (ILD) remains among the leading causes of SSc-related mortality with still few therapeutic effective strategies. In patients with crystallin silica exposure, SSc is recognized as an occupational disease according to the French social security system (Table 25A of the general insurance regimen). Lympho-ablative or myeloablative immunosuppression followed by autologous hematopoietic stem-cell transplantation (aHSCT) is the only therapeutic approach with demonstrated efficacy, improved survival with disease modifying effects on SSc-fibrotic manifestations (skin disease and ILD) and quality of life. A documented past and/or present occupational silica exposure, with extensive exposure and/or silica-related ILD and/or with persistent silica content in the broncho-alveolar lavage fluid are contra-indications to aHSCT in SSc patients, due to the risk of silica-related malignancy or of SSc relapse. This article aims to discuss alternative options in SSc patients with a history of silica exposure, and how innovative cellular therapies (mesenchymal stromal cells, CAR cells) could represent new therapeutic options for these patients.

Occupational exposure to silica and risk of gastrointestinal cancers: a systematic review and meta-analysis of cohort studies.

Although silica is a proven lung carcinogen, there is no convincing evidence linking crystalline silica to gastrointestinal malignancies. We detailedly searched studies on the link between gastrointestinal malignancies and occupational silica exposure. Studies published between 1987 and 2023 were found by searching PubMed, Scopus, Cochrane Library, and Web of Science databases. Further studies were included from reference searching. We conducted a meta-analysis of the incidence and mortality of gastrointestinal malignancies and occupational silica exposure. We computed pooled-risk estimates using random effects models. Egger's regression asymmetry test and a funnel plot were used to identify publication bias. Moreover, sensitivity analysis and subgroup analysis were out. We identified 40 research with individuals from 13 different countries. The results indicate that occupational silica exposure raises the risk of gastric and esophageal cancer incidence, with pooled standardized incidence ratio of 1.35 (95% CI 1.21-1.51, p < 0.001), 1.31 (95% CI 1.04-1.65, p = 0.023), respectively, but there was a lack of statistically significant relationship between standardized mortality ratio. In addition, we found that silica exposure did not increase the risk of colorectal and pancreatic cancers. Occupational silica exposure was found to increase the risk of liver cancer, with pooled SIR and SMR of 1.19 (95% CI 1.04-1.35, p = 0.009), 1.24 (95% CI 1.03-1.49, p = 0.026), respectively. We discovered a link between occupational silica exposure and gastrointestinal malignancies, with cancers of the liver, stomach, and esophagus being the most prevalent. Colorectal and pancreatic cancer were not linked to occupational silica exposure.

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships.

The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Prevalence and determinants of evidence of silicosis and impaired lung function among small scale tanzanite miners and the peri-mining community in northern Tanzania.

Limited data among miners in Tanzania suggests prevalence of silicosis, obstructive lung disease and restrictive lung disease to be around 1.6%, 1.9% and 8.8% respectively. Our study aimed to determine the prevalence and factors associated with silicosis and impaired lung function among tanzanite mining community in northern Tanzania. We conducted a cross-sectional study, involving 330 miners and 330 peri-mining community members in Mererani mines. Silicosis was defined based on study participants' history of exposure to mining dust and digital chest radiological findings with reference to the 2011 ILO classification of pneumoconiosis. Impaired lung function was determined by spirometry using American Thoracic Society/European Respiratory Society recommended system 3. Association between evidence of silicosis/impaired lung function and presumed risk factors were determined using binary logistic regression analyses. The study found that 99/330 (30.0%) of miners had silicosis. Total of 65 (9.8%) participants had impaired lung function, of whom 29 (4.4%) had Chronic Obstructive Pulmonary Disease, 32 (4.8%) had restrictive lung disease and 4 (0.6%) had both obstructive and restrictive lung diseases. Unexpectedly, miners who have worked for more than 10years and those worked for 6 to 10 years had 64% (aOR 0.34, CI = 0.17-0.67, p = 0.002) and 48% (aOR 0.52, CI = 0.30-0.89, p = 0.018) lower odds of having silicosis respectively compared those worked for up to 5 years. Participants with more than 10 years of work duration had more than 3-times higher odds of impaired lung function compared to those who had worked for up to 5 years (aOR 3.11, CI = 1.53-6.34, p<0.002). We found a concerningly high prevalence of silicosis despite short durations of exposure to occupational silica dust. Immediate dust control measures including deployment of wet drilling, wearing of personal protective equipment and regular monitoring of dust exposure need to be enforced by the Occupational Safety and Health Authority-Tanzania.

ERASMUS SYNDROME: AN INTERFACE BETWEEN ENVIRONMENT AND AUTOIMMUNITY

Introduction: Erasmus Syndrome (ES) is a rare condition in which Systemic Sclerosis (SSc) is caused by exposure to silica. The term Erasmus Syndrome was coined after cases of SSc were found among gold miners in South Africa. In India, there is a paucity of such reported cases which might be more due to unawareness of the entity rather than low prevalence. Though the treatment remains the same, ES provides a template for the study of interactions between the environment and our immune system. Case: We present the case of a male patient diagnosed with systemic sclerosis, who was referred to the Rheumatology Clinic of our institution, and which on further evaluation revealed the cause as occupational silica exposure thus changing the diagnosis to ES. Conclusion: We conclude that ES represents an interaction of the environment and the human immune system, with the environment being the factor in the earlier and more severe progression of the disease. We also underline the importance of awareness of this entity among clinicians and of taking a proper history, especially the occupational history of any patient of SSc.

Silicosis and silicotuberculosis among respiratory hospital admissions: A cross-sectional survey in northern Tanzania.

There is little evidence describing respiratory disease among 40.5 million small-scale miners worldwide. To describe the prevalence and clinical characteristics of adult respiratory inpatients with silicosis and silicotuberculosis in a tertiary hospital in Tanzania that serves a small-scale mining region. In this retrospective, cross-sectional survey, patient files from admissions between 2010 and 2020 were opportunistically selected and included if a respiratory diagnosis had been made. Of 223 patients with respiratory conditions, 32 (14.3%; 95% confidence interval (CI) 10.0 - 19.6) were diagnosed with silicosis and 17 (7.6%; 95% CI 4.5 - 11.9) with silicotuberculosis. Mining was the most frequent occupation in those with silicosis (n=15/32; 46.9%) and silicotuberculosis (n=15/17; 88.2%). Of those with silicosis or silicotuberculosis, 26/49 (53.1%) were aged <45 years. Our study suggests that silicosis and silicotuberculosis are common among male and female respiratory inpatients with occupational exposure. The study highlights the role of occupational exposures in respiratory disease in developing economies. What the study adds. This retrospective, cross-sectional survey describes the prevalence of silicosis and silicotuberculosis among adult respiratory inpatients admitted to a tertiary hospital in northern Tanzania. It is the first study to describe the prevalence and characteristics of respiratory inpatients with silicosis and silicotuberculosis in a small-scale mining region of Africa. A high prevalence of silicosis (14.3%) and silicotuberculosis (7.6%) was found. Patients were often aged <45 years, and the majority required oxygen therapy.Implications of the findings. The high prevalence of advanced silicosis and silicotuberculosis in miners presenting at a young age raises concerns about high occupational silica exposures and, importantly, suggests a need for community-based research, which our team is planning to undertake.

Airborne occupational exposures associated with pulmonary sarcoidosis: a systematic review and meta-analysis

The aetiology and pathophysiology of sarcoidosis is ill defined—current hypotheses centre on complex genetic–immune–environmental interactions in an individual, triggering a granulomatous process. The aim of this systematic review is to...

Global burden of tracheal, bronchus, and lung cancer attributable to occupational carcinogens in 204 countries and territories, from 1990 to 2019: results from the global burden of disease study 2019

Background Occupational-related cancers are a substantial global health issue. The largest proportion of occupational-related cancers is tracheal, bronchus, and lung (TBL) cancer. This study aimed to explore the geographical and temporal trends in occupational carcinogens related to TBL cancer. Methods Data on TBL cancer attributable to occupational carcinogens were collected from the Global Burden of Disease Study 2019. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs), and corresponding average annual percentage change (AAPC) were evaluated and stratified by geographic location, socio-demographic index (SDI) quintiles, age, and sex. Results Globally, ASRs of deaths and DALYs in TBL cancer attributable to occupational carcinogens showed a downward trend (AAPC = − 0.69%, − 1.01%) while increases were observed in the low, low-middle, and middle SDI quintiles. Although males accounted for 82.4% and 81.5% of deaths and DALYs in 2019, respectively, it showed an upward trend of ASRs in females (AAPC = 0.33%, 0.02%). Occupational exposure to asbestos, silica and diesel engine exhaust were the top three causes of age-standardized TBL cancer deaths and DALYs. Over the past three decades, the percentage of age-standardized TBL cancer deaths and DALYs attributable to occupational asbestos and silica exposure decreased by 18.24, 6.71 and 20.52%, 4.00% globally, but increased significantly in lower SDI regions, while the burden attributable to occupational diesel engine exhaust exposure increased by 32.76, 37.23% worldwide. Conclusions Occupational exposure remains an important risk factor for TBL cancer. The burden of TBL cancer attributable to occupational carcinogens showed obvious heterogeneity which decreased in higher SDI but increased in lower SDI regions. The burden of males was significantly higher than females, but the females showed an increasing trend. Occupational exposure to asbestos was the main causes of the burden. Therefore, effective prevention and control measures tailored to local conditions are necessary.

Potential consequences of screening of occupational silica dust exposed workers for early detection of silicosis/silico-tuberculosis using a novel biomarker, club cell protein-16, with possible intervention by repurposing metformin

Earlier, a study conducted by the Indian Council of Medical Research – National Institute of Occupational Health (ICMR-NIOH), India, evidenced that CC16 may be used as a proxy marker and screening tool for early detection and progression of silica-induced lung damage. Once CC16 indicates early silicosis, it needs to be confirmed by chest radiography. Next, ICMR-NIOH and ICMR-National Institute of Virology (ICMR-NIV) jointly developed a semi-quantitative and point-of-care CC16 detection kit using lateral flow immune chromatography. The said test can be done from one drop of blood collected through a finger prick. All trained peripheral healthcare workers can screen the silica dust-exposed workers periodically, under the national silicosis control program. Once early silicosis is detected, their sputum may be examined periodically by CB-NAAT/True-NAT for early detection of silicotuberculosis. The serum CC-16 detection kit is the first of its kind for early detection of silicosis through periodic screening, which is approved by the Indian Council of Medical Research, Ministry of Health, Govt. of India. Unless silicosis is controlled, elimination of TB appears to be difficult in India as there is a huge burden of silicosis including sub-radiological silicosis in India and considering the fact that silicosis is a stronger risk factor for lung tuberculosis due to its progressive declining effect of lung immunity. Since occupational silica dust exposure facilitates progressive fibrosis of lung tissue, a clinical trial using metformin may be the need of the day as animal experiments have already shown metformin's anti-fibroblastic effect in silica-induced animals.

Understanding the pathogenesis of occupational coal and silica dust-associated lung disease.

Workers in the mining and construction industries are at increased risk of respiratory and other diseases as a result of being exposed to harmful levels of airborne particulate matter (PM) for extended periods of time. While clear links have been established between PM exposure and the development of occupational lung disease, the mechanisms are still poorly understood. A greater understanding of how exposures to different levels and types of PM encountered in mining and construction workplaces affect pathophysiological processes in the airways and lungs and result in different forms of occupational lung disease is urgently required. Such information is needed to inform safe exposure limits and monitoring guidelines for different types of PM and development of biomarkers for earlier disease diagnosis. Suspended particles with a 50% cut-off aerodynamic diameter of 10 µm and 2.5 µm are considered biologically active owing to their ability to bypass the upper respiratory tract's defences and penetrate deep into the lung parenchyma, where they induce potentially irreversible damage, impair lung function and reduce the quality of life. Here we review the current understanding of occupational respiratory diseases, including coal worker pneumoconiosis and silicosis, and how PM exposure may affect pathophysiological responses in the airways and lungs. We also highlight the use of experimental models for better understanding these mechanisms of pathogenesis. We outline the urgency for revised dust control strategies, and the need for evidence-based identification of safe level exposures using clinical and experimental studies to better protect workers' health.

Some pleural effusions labeled as idiopathic could be produced by the inhalation of silica.

ObjectivesExposure to silica nanoparticles has been associated with pleural effusions (PEs) in animal models and case series. We hypothesized that some PEs labelled as “idiopathic” could, in fact, be secondary to inhalation of silica.MethodsA retrospective case control study was designed utilizing a prospectively maintained pleural database. Cases, represented by idiopathic PEs, were matched by age and gender to control patients who had been diagnosed with malignant, cardiac, or infectious PEs. A survey consisting of questions about occupational life and possibility of silica inhalation was conducted. In a subgroup of patients, pleural fluid concentrations of silica were quantified by plasma atomic emission spectrometry analysis. Also, the pleural biopsy of a silica-exposed case was subjected to an energy dispersive X-ray spectroscopy (EDX) to identify the mineral, the size of which was determined by electron microscopy.ResultsA total of 118 patients (59 cases and 59 controls) completed the survey. There were 25 (42%, 95% CI 31–55%) and 13 (22%, 95% CI 13–34%) silica-exposed workers in case and control groups, respectively. The exposure attributable fraction was 0.62 (95% CI 0.14–0.83). Four of eight exposed cases showed detectable levels of silica in the pleural fluid (mean 2.37 mg/L), as compared to none of 16 tested controls. Silica nanoparticles of 6–7 nm were identified in the pleural biopsy of an exposed case patient.ConclusionsIt is plausible that some idiopathic PEs could actually be caused by occupational silica inhalation.

High-fat western diet-consumption alters crystalline silica-induced serum adipokines, inflammatory cytokines and arterial blood flow in the F344 rat

Adipose tissue (AT) plays a central role in the maintenance of whole-body energy homeostasis through release of adipokines. High-fat Western diet (HFWD)-consumption contributes to obesity, disruption of adipocyte metabolism, chronic systemic inflammation, and metabolic dysfunction (MetDys). MetDys is associated with impaired lung function, pulmonary hypertension, and asthma. Thirty-five percent of adults in the U.S. have MetDys, yet the impact of MetDys on susceptibility to occupational hazards is unknown. The aim of this study was to determine the potential of HFWD-consumption to alter inhaled crystalline silica dust-induced metabolic responses. Six-wk old male F344 rats were fed a HFWD (45 kcal % fat, sucrose 22.2 % by weight) or standard rat chow (STD, controls), and exposed to silica-inhalation (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m3) or filtered air. Indices of MetDys and systemic inflammation were measured at 0, 4, and 8 wk following cessation of silica exposure. At 8 wk post-exposure, silica reduced serum leptin and adiponectin levels, and increased arterial pulse frequency. HFWD-consumption induced weight gain, altered adipokines, liver, kidney, and pancreatic function, and increased tail artery blood flow. At 8 wk in HFWD + SIL-treated animals, the levels of serum pro-inflammatory cytokines (IFN-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13) were increased compared to STD + SIL but were less than HFWD + AIR-induced levels. In conclusion, consumption of a HFWD altered silica-induced metabolic responses and silica exposure disrupted AT endocrine function. These findings demonstrate previously unknown interactions between HFWD-consumption and occupational silica exposure.

A rapid point of care CC16 kit for screening of occupational silica dust exposed workers for early detection of silicosis/silico-tuberculosis

Silicosis is an irreversible, incurable and progressive occupational disease caused by prolonged exposure to crystalline-silica dust while working in the relevant industries. Conventionally diagnosis is done by chest radiology, often in an advanced stage as early symptoms often go unnoticed. Early detection and necessary intervention (secondary prevention) could be a realistic possible control strategy for controlling silicosis as no effective treatment is available to stop and/or reverse the pathological process. Additionally, these patients are also vulnerable to pulmonary tuberculosis, which often becomes difficult to treat and with uncertain treatment outcome. Considering India has a huge burden of silicosis and silico-tuberculosis, a rapid and inexpensive screening method was realized to be an urgent need for early detection of silicosis among silica dust exposed workers. Serum club cell protein 16 (CC16) is evidenced to be a useful proxy screening marker for early detection of silicosis as evidenced from the recent research work of ICMR-National Institute of Occupational Health (ICMR-NIOH), India. In this study a lateral-flow assay for semi-quantitative estimation of serum CC16 level was developed. The detection was performed using gold nanoparticles conjugated anti-CC16 monoclonal antibodies. A sum of 106 serum samples was tested to do the performance evaluation of the assay. A concentration of 6 ng/ml or less produced one band, 6.1–9 ng/ml produced two bands, while more than 9 ng/ml produced all the three bands at the test zone. The sensitivity of the assay was 100% while the specificity was 95%. This assay may be used as a sensitive tool for periodic screening of silica dust exposed vulnerable workers for early detection of silicosis in them.

TOFACITINIB - BOON OR A BANE?

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Tofacitinib (Xeljanz) is common and popular Disease Modifying Anti-Rheumatic Drug used in the treatment of moderate to severe Rheumatoid Arthritis (RA) that was approved by US FDA in 2012. It now comes with a new black-box warning for venous thromboembolism (VTE). We present a patient taking Tofacitinib as well as an oral anticoagulant that developed pulmonary embolism (PE) after receiving his first COVID-19 vaccine. CASE PRESENTATION: An 80-year-old white male with severe RA on Tofacitinib (previously failed treatment with Methotrexate and Infliximab), mild interstitial lung disease likely related to occupational silica exposure, severe Chronic Obstructive Pulmonary Disease (COPD) with oxygen dependency, 50 pack-year smoking history (quit in 2016), coronary artery disease, atrial flutter on Rivaroxaban presents to ED for worsening shortness of breath. He had just received his first COVID-19 vaccine manufactured by Moderna two weeks prior. Vital signs include; heart rate 127 bpm, respirations 40 per minute, SpO2 84% on 6 LPM oxygen and fever of 101.2 F. Pertinent labs include WBC 12.4, Lactic Acid 3, BNP 175, Troponin 0.02. Chest X-ray revealed edema and/ or atypical pneumonia, but COVID-19 screen was negative. He received IV Solumedrol and Cefepime, before being admitted. Overnight he developed new onset chest pain with increased O2 requirements up to 15 LPM. CT Chest was immediately pursued revealing right upper lobe and bilateral lower lobe segmental pulmonary emboli without right ventricular strain. He was started on a heparin drip. Tofacitinib was stopped on the recommendation of his Rheumatologist and he was discharged on Apixaban. DISCUSSION: Tofacitinib is a JAK 1-3 inhibitor causing inhibition of the CD 16/56+ natural killer cells, serum IgG-IgM-IgA and CRP. Higher doses of Tofacitinib are associated with an increased incidence of DVT/PE in elderly population, with at least one cardiovascular risk factor [1]. In study A3921133, a higher frequency of PE and all-cause mortality was seen in higher dose of Tofacitinib (10 Mg BID) when compared to TNF inhibitors [2]. In another Long-term Extension (LTE) study involving 7061 patients taking Tofacitinib, VTE was reported in 59 (0.8%) patients with an IR (95% CI) of 0.3 (0.2 to 0.3), DVT was reported in 36 (0.5%) patients (IR 0.2 [95% CI 0.1 to 0.2]) and PE in 28 (0.4%), [2]. FDA has issued a 'Boxed warning’ regarding the risk of thrombosis with 10 mg BID dose of Tofacitinib [3]. CONCLUSIONS: Clinicians are strongly urged to evaluate the risk of DVT/PE before initiating higher dose of Tofacitinib in patients greater than 50 years old with at least one cardiovascular risk factor. In our case, another confounding aspect is the incidence of PE despite treatment with an oral anticoagulant. The thrombogenic potential of Tofacitinib should strongly be explored as an independent risk factor for PE by clinicians. REFERENCE #1: [1] Mease, Philip, et. Al; Incidence of Venous and Arterial Thromboembolic Events Reported in Tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis Development Programs and from Real-World Data, 2020, Annals of Rheumatic Disease, 79(11): 1400-1413, DOI: 10.1136/annrheumdis-2019-216761 REFERENCE #2: [2] Cohen, Stanley; et Al; Long-term Safety of Tofacitinib up to 9.5 years: A Comprehensive Integrated Analysis of the Rheumatoid Arthritis Clinical Development Programme, 2020, Rheumatic and Musculoskeletal Disease, 6(3):e001395, DOI: 10.1136/rmdopen-2020-001395 REFERENCE #3: [3] U.S. Food and Drug Administration (FDA), Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib), 2021, Drug Safety Communication, Retrieved from; https://www.fda.gov/drugs/drug-safety-and-availability/initial-safety-trial-results-find-increased-risk-serious-heart-related-problems-and-cancer-arthritis DISCLOSURES: No relevant relationships by Mahmoud Amarna, source=Web Response No relevant relationships by Camelia Chirculescu, source=Web Response No relevant relationships by Johnston Hospital, source=Web Response No relevant relationships by Rakesh Patel, source=Web Response No relevant relationships by Mallika Velichety, source=Web Response

Effect of Occupational Silica Exposure on Stone Crusher Workers

The Shankargarh town of Prayagraj district of Uttar Pradesh, India, is well known for its high quality silica sand and large scale surface mining. Evaluation of health of crusher workers was conducted in the stone crushers units of Shankargarh villages to access the silica dust exposure risk on stone crusher workers and nearby residents. These areas are covered with Granite and Silica sand. The various crushing operations involved in stone crushing e.g. blasting, manual cutting, crushing and transportation emit fugitive stone dust. These fine aerosol of stone dust causes health problems among the stone crusher workers. Health survey e.g. general clinical examination, blood sample test, sounds level measurement was carried out to access the extent of the damage caused to the workers.

Geographic distribution and environmental triggers of systemic sclerosis cases from 2 large academic tertiary centers in Massachusetts

To the Editor: Systemic sclerosis (SSc) is a chronic autoimmune sclerosing disease with the highest case fatality rate among connective tissue diseases.1Feghali-Bostwick C.A. Varga J. Systemic Sclerosis.in: Bradshaw R.A. Dennis E.A. Handbook of Cell Signaling. 2nd ed. Academic Press, 2010: 2913-2917Crossref Scopus (1) Google Scholar Since the 1980s, the annual incidence rates in North America have increased from 1.7 to 2.7 per 100,000 individuals.2Bergamasco A. Hartmann N. Wallace L. Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease.Clin Epidemiol. 2019; 11: 257-273Crossref PubMed Scopus (66) Google Scholar Although the exact pathogenesis of SSc remains unclear, environmental triggers have been hypothesized to provoke disease development among genetically predisposed hosts.3Barnes J. Mayes M.D. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.Curr Opin Rheumatol. 2012; 24: 165-170Crossref PubMed Scopus (212) Google Scholar,4McCormic Z.D. Khuder S.S. Aryal B.K. Ames A.L. Khuder S.A. Occupational silica exposure as a risk factor for scleroderma: a meta-analysis.Int Arch Occup Environ Health. 2010; 83: 763-769Crossref PubMed Scopus (82) Google Scholar The assessment of high-prevalence geographic clusters may be a crucial first step in cause identification. Our objectives were to analyze SSc hotspots in Massachusetts and identify possible environmental triggers. The research patient data registry was utilized to identify 4579 potential SSc cases and zip codes from medical records between 1989 and 2019 of Massachusetts General Hospital and Brigham and Women's Hospital. Cases confirmed by dermatologists or rheumatologists were included (n = 2196). The period prevalence was calculated based on the population per zip code. QGIS3.10, a geospatial program, was used to create and analyze SSc distribution and prevalence maps (Fig 1). These maps were compared to environmental toxins and social justice maps to determine trends in etiologic triggers and demographic clusters. Statistical analysis was performed using 2 sample t tests. Hazardous waste facilities (P = .0039) and oil release or disposal sites (P = .0203) were significantly associated with a higher SSc prevalence (Fig 2). Although the association between chemical release sites and SSc prevalence was not independently significant (P = .3166), a spatial correlation was found to exist. Exposure to all 3 sites together posed a significantly increased SSc risk (P = .0002). Disease hotspots showed greater particulate pollution levels and were in proximity to ash pollution and combustion facilities (Supplemental Fig 1 available via Mendeley at https://data.mendeley.com/datasets/59zfn6fdb2/2). The maps of low-income and minority communities demonstrated a spatial relationship with SSc hotspots, suggesting a possible association between socioeconomic factors and disease (Supplemental Fig 2 available via Mendeley at https://data.mendeley.com/datasets/59zfn6fdb2/2).5Environmental justice populations in Massachusetts | Mass.gov.https://www.mass.gov/info-details/environmental-justice-populations-in-massachusettsDate accessed: January 27, 2021Google Scholar The presence of SSc regional clustering and increased density of industry and waste sites in these areas suggest that environmental pollutants play a critical role in disease development. Additionally, the clustering of SSc hotspots and environmental pollutants around low-income and minority neighborhoods indicates that these residents face a disproportionate burden of toxin exposure and disease. High-SSc prevalence pockets in Central and Western Massachusetts with few or no direct toxin sites may be impacted by their surrounding environmental factors, such as water sources collecting precipitated pollutants from nearby facilities or by cross-state pollution, both waterborne and airborne. Another possible explanation for SSc regional clustering is the social drift hypothesis, suggesting that those with chronic diseases are more likely to reside in low-income areas because of disease burden. The study limitations include potential confounders contributing to disease, such as genetic predispositions, sociodemographic factors, and proximity bias. Finally, our study demonstrated a correlation but could not prove causation, making further study of this important topic crucial. Further investigations, including wider geographies and more diverse patient populations, are warranted. Ultimately, this research may provide a greater understanding of the potential role of environmental toxins in SSc onset. Furthermore, it may be used as an advocate for environmental and health policy reforms to protect communities disproportionately burdened by their exposure to environmental toxins and their adverse health effects. None disclosed.

Occupational silica exposure in an Australian systemic sclerosis cohort.

To determine the frequency of self-reported occupational exposure to silica in SSc patients enrolled in the Australian Scleroderma Cohort Study, and to compare the disease characteristics of the silica-exposed patients with those of the non-exposed patients. Data collected over a 12-year period from 1670 SSc patients were analysed. We compared the demographic and clinical characteristics of those who reported occupational silica exposure with those who did not. A subgroup analysis of male patients was performed, as well as a multivariable analysis of correlates of silica exposure. Overall, 126 (7.5%) of the cohort reported occupational silica exposure. These individuals were more likely to be male (73 of 231, i.e. 31.6% males exposed) and to have worked in mining and construction industries. Those who reported silica exposure were younger at the onset of SSc skin involvement [odds ratio (OR) 0.9, P = 0.02], of male gender (OR 14.9, P < 0.001), have joint contractures (OR 1.8, P = 0.05) and have higher physical disability as defined by scleroderma HAQ (OR 1.4, P = 0.01). The highest percentage of silica exposure was found in males. These patients were more likely to have the presence of certain clinical manifestations and Scl-70 antibody, which is known to confer a poor prognosis. These findings support the association between occupational silica exposure and the subsequent development of SSc. Further investigation is required to describe the range of clinical manifestations and disease course, including prognosis and treatment response, in those diagnosed with occupationally induced SSc compared with idiopathic SSc.

Sarcoidosis and silica dust exposure among men in Sweden: a case–control study

ObjectiveTo determine whether occupational exposure to silica dust is associated with an increased risk of developing sarcoidosis.DesignCase–control study of all individuals between 20 and 65 years of age diagnosed with...