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Occupational and Environmental Medicine Nov 2020Work-related lung diseases (WRLDs) are entirely preventable. To assess the impact of WRLDs on the US transplant system, we identified adult lung transplant recipients...
OBJECTIVES
Work-related lung diseases (WRLDs) are entirely preventable. To assess the impact of WRLDs on the US transplant system, we identified adult lung transplant recipients with a WRLD diagnosis specified at the time of transplant to describe demographic, payer and clinical characteristics of these patients and to assess post-transplant survival.
METHODS
Using US registry data from 1991 to 2018, we identified lung transplant recipients with WRLDs including coal workers' pneumoconiosis, silicosis, asbestosis, metal pneumoconiosis and berylliosis.
RESULTS
The frequency of WRLD-associated transplants has increased over time. Among 230 lung transplants for WRLD, a majority were performed since 2009; 79 were for coal workers' pneumoconiosis and 78 were for silicosis. Patients with coal workers' pneumoconiosis were predominantly from West Virginia (n=31), Kentucky (n=23) or Virginia (n=10). States with the highest number of patients with silicosis transplant were Pennsylvania (n=12) and West Virginia (n=8). Patients with metal pneumoconiosis and asbestosis had the lowest and highest mean age at transplant (48.8 and 62.1 years). Median post-transplant survival was 8.2 years for patients with asbestosis, 6.6 years for coal workers' pneumoconiosis and 7.8 years for silicosis. Risk of death among patients with silicosis, coal workers' pneumoconiosis and asbestosis did not differ when compared with patients with idiopathic pulmonary fibrosis.
CONCLUSIONS
Lung transplants for WRLDs are increasingly common, indicating a need for primary prevention and surveillance in high-risk occupations. Collection of patient occupational history by the registry could enhance case identification and inform prevention strategies.
Topics: Berylliosis; Humans; Kaplan-Meier Estimate; Lung Diseases; Lung Transplantation; Male; Middle Aged; Occupational Diseases; Pneumoconiosis; Registries; Silicosis; Survival Analysis; United States
PubMed: 32859693
DOI: 10.1136/oemed-2020-106578 -
Sangyo Eiseigaku Zasshi = Journal of... Mar 2021Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications... (Review)
Review
OBJECTIVES
Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan.
METHODS
We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan.
RESULTS
It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important.
CONCLUSIONS
It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.
Topics: Berylliosis; Beryllium; Chronic Disease; Female; Humans; Japan; Lung Neoplasms; Male; Occupational Diseases; Occupational Exposure; Occupational Health; Workplace
PubMed: 32788509
DOI: 10.1539/sangyoeisei.2020-030-A -
American Journal of Respiratory and... Oct 2020A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells...
A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients. To measure ABC-like cell percentages in patients with lung granulomatous diseases. Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet. ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood. Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.
Topics: Adult; Aged; Aged, 80 and over; Alveolitis, Extrinsic Allergic; B-Lymphocyte Subsets; Berylliosis; Bronchoalveolar Lavage Fluid; CD11c Antigen; Case-Control Studies; Female; Humans; Male; Membrane Proteins; Middle Aged; Receptors, Cell Surface; Receptors, Complement 3d; Receptors, Fc; Receptors, Immunologic; Sarcoidosis, Pulmonary; T-Box Domain Proteins; Young Adult
PubMed: 32501729
DOI: 10.1164/rccm.201911-2151OC -
Frontiers in Immunology 2020Pulmonary sarcoidosis and chronic beryllium disease (CBD) are inflammatory granulomatous lung diseases defined by the presence of non-caseating granulomas in the lung.... (Review)
Review
Pulmonary sarcoidosis and chronic beryllium disease (CBD) are inflammatory granulomatous lung diseases defined by the presence of non-caseating granulomas in the lung. CBD results from beryllium exposure in the workplace, while the cause of sarcoidosis remains unknown. CBD and sarcoidosis are both immune-mediated diseases that involve Th1-polarized inflammation in the lung. Beryllium exposure induces trafficking of dendritic cells to the lung in a mechanism dependent on MyD88 and IL-1α. B cells are also recruited to the lung in a MyD88 dependent manner after beryllium exposure in order to protect the lung from beryllium-induced injury. Similar to most immune-mediated diseases, disease susceptibility in CBD and sarcoidosis is driven by the expression of certain MHCII molecules, primarily in CBD and several alleles in sarcoidosis. One of the defining features of both CBD and sarcoidosis is an infiltration of activated CD4+ T cells in the lung. CD4+ T cells in the bronchoalveolar lavage (BAL) of CBD and sarcoidosis patients are highly Th1 polarized, and there is a significant increase in inflammatory Th1 cytokines present in the BAL fluid. In sarcoidosis, there is also a significant population of Th17 cells in the lungs that is not present in CBD. Due to persistent antigen exposure and chronic inflammation in the lung, these activated CD4+ T cells often display either an exhausted or anergic phenotype. Evidence suggests that these T cells are responding to common antigens in the lung. In CBD there is an expansion of beryllium-responsive TRBV5.1+ TCRs expressed on pathogenic CD4+ T cells derived from the BAL of CBD patients that react with endogenous human peptides derived from the plexin A protein. In an acute form of sarcoidosis, there are expansions of specific TRAV12-1/TRBV2 T cell receptors expressed on BAL CD4+ T cells, indicating that these T cells are trafficking to and expanding in the lung in response to common antigens. The specificity of these pathogenic CD4+T cells in sarcoidosis are currently unknown.
Topics: Adaptive Immunity; Animals; Berylliosis; Chronic Disease; HLA-DP beta-Chains; Humans; Lung; Sarcoidosis, Pulmonary; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 32256501
DOI: 10.3389/fimmu.2020.00474 -
JCI Insight May 2020Chronic beryllium disease (CBD) is a metal hypersensitivity/autoimmune disease in which damage-associated molecular patterns (DAMPs) promote a break in T cell tolerance...
Chronic beryllium disease (CBD) is a metal hypersensitivity/autoimmune disease in which damage-associated molecular patterns (DAMPs) promote a break in T cell tolerance and expansion of Be2+/self-peptide-reactive CD4+ T cells. In this study, we investigated the mechanism of cell death induced by beryllium particles in alveolar macrophages (AMs) and its impact on DAMP release. We found that phagocytosis of Be led to AM cell death independent of caspase, receptor-interacting protein kinases 1 and 3, or ROS activity. Before cell death, Be-exposed AMs secreted TNF-α that boosted intracellular stores of IL-1α followed by caspase-8-dependent fragmentation of DNA. IL-1α and nucleosomal DNA were subsequently released from AMs upon loss of plasma membrane integrity. In contrast, necrotic AMs released only unfragmented DNA and necroptotic AMs released only IL-1α. In mice exposed to Be, TNF-α promoted release of DAMPs and was required for the mobilization of immunogenic DCs, the expansion of Be-reactive CD4+ T cells, and pulmonary inflammation in a mouse model of CBD. Thus, early autocrine effects of particle-induced TNF-α on AMs led to a break in peripheral tolerance. This potentially novel mechanism may underlie the known relationship between fine particle inhalation, TNF-α, and loss of peripheral tolerance in T cell-mediated autoimmune disease and hypersensitivities.
Topics: Animals; Berylliosis; CD4-Positive T-Lymphocytes; Cell Line; Chronic Disease; Female; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Tumor Necrosis Factor-alpha
PubMed: 32255768
DOI: 10.1172/jci.insight.134356 -
Annals of Work Exposures and Health Oct 2019Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify...
OBJECTIVES
Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD).
METHODS
In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines.
RESULTS
Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS.
CONCLUSION
Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.
Topics: Adult; Air Pollutants, Occupational; Benchmarking; Berylliosis; Beryllium; Cross-Sectional Studies; Female; Gloves, Protective; Humans; Inhalation Exposure; Male; Manufacturing and Industrial Facilities; Middle Aged; Occupational Exposure; Prevalence; Regression Analysis; Risk Factors; Skin; Young Adult
PubMed: 31504146
DOI: 10.1093/annweh/wxz064 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2019The interplay of metal ions with polysaccharides is important for the immune recognition in the lung. Due to the localization of beryllium associated diseases to the...
The interplay of metal ions with polysaccharides is important for the immune recognition in the lung. Due to the localization of beryllium associated diseases to the lung, it is likely that beryllium carbohydrate complexes play a vital role for the development of berylliosis. Herein, we present a detailed study on the interaction of Be ions with fructose and glucose as well as simpler biomimetic ligands, which emulate binding motives of saccharides. Through NMR and IR spectroscopy as well as single-crystal X-ray diffraction, complemented by competition reactions we were able to determine a distinctive trend in the binding affinity of these ligands. This suggests that under physiological conditions beryllium ions are only bound irreversibly in glycoproteins or polysaccharides if a quasi ideal tetrahedral environment and κ -coordination is provided by the respective biomolecule. Furthermore, Lewis acid induced conversions of the ligands and an extreme increase in the Brønstedt acidity of the present OH-groups imply that upon enclosure of Be , alterations may be induced by the metal ion in glycoproteins or polysaccharides. In addition the frequent formation of Be-O-heterocycles indicates that multinuclear beryllium compounds might be the actual trigger of berylliosis. This investigation on beryllium coordination chemistry was supplemented by binding studies of selected biomimetic ligands with Al , Zn , Mg , and Li , which revealed that none of these beryllium related ions was tetrahedrally coordinated under the give conditions. Therefore, studies on the metabolization of beryllium compounds cannot be performed with other hard cations as a substitute for the hazardous Be .
Topics: Beryllium; Biomimetic Materials; Carbohydrates; Ions; Ligands; Magnetic Resonance Spectroscopy; Molecular Conformation
PubMed: 31498482
DOI: 10.1002/chem.201903439 -
The Pan African Medical Journal 2018Chronic beryllium disease (CBD) is an occupational illness with varying severity. In this report, we describe a 27 year old man, glassblower, who developed a fatal CBD...
Chronic beryllium disease (CBD) is an occupational illness with varying severity. In this report, we describe a 27 year old man, glassblower, who developed a fatal CBD after six months of unknown Beryllium's exposure. The diagnosis was suspected on histological examination and then consolidated by confirmation of Beryllium's exposure at the working area. Physicians should be aware of the potential risk to develop CBD in glassblowers. These workers should benefit from early medical surveillance using the Beryllium lymphocyte proliferation test (BeLPT) and therefore from suitable management.
Topics: Adult; Berylliosis; Beryllium; Chronic Disease; Humans; Lung Diseases, Interstitial; Male; Occupational Diseases; Occupational Exposure
PubMed: 31011396
DOI: 10.11604/pamj.2018.31.95.14831 -
The Journal of Physical Chemistry. B Feb 2019Beryllium has multiple industrial applications but exposure to its dust during manufacturing is associated with developing chronic inflammation in lungs known as...
Beryllium has multiple industrial applications but exposure to its dust during manufacturing is associated with developing chronic inflammation in lungs known as berylliosis. Besides binding to specific alleles of MHC-II, Be was recently found to compete with Ca for binding sites on phosphatidylserine-containing membranes and inhibit recognition of this lipid by phagocytes. Computational studies of possible molecular targets for this small toxic dication are impeded by the absence of a reliable force field. This study introduces parameters for Be for the CHARMM36 additive force field that represent interactions with water, including free energy of hydration and ion-monohydrate interaction energy and separation distance; and interaction parameters describing Be affinity for divalent ion binding sites on lipids, namely phosphoryl and carboxylate oxygens. Results from isothermal titration calorimetry experiments for the binding affinities of Be to dimethyl phosphate and acetate ions reveal that Be strongly binds to phosphoryl groups. Revised interaction parameters for Be with these types of oxygens reproduce experimental affinities in solution simulations. Surface tensions calculated from simulations of DOPS monolayers with varied concentrations of Be are compared with prior results from Langmuir monolayer experiments, verifying the compacting effect that produces greater surface tensions (lower pressures) for Be-bound monolayers at the same surface area in comparison with K. The new parameters will enable simulations that should reveal the mechanism of Be interference with molecular recognition and signaling processes.
Topics: Beryllium; Binding Sites; Calorimetry; Ions; Molecular Dynamics Simulation; Phosphatidylserines; Surface Tension; Thermodynamics; Water
PubMed: 30681857
DOI: 10.1021/acs.jpcb.8b11884 -
Genes and Immunity Jul 2019Previously we showed that alveolar macrophages (AMs) from patients with chronic beryllium disease (CBD) and beryllium sensitization (BeS) demonstrated significantly...
Previously we showed that alveolar macrophages (AMs) from patients with chronic beryllium disease (CBD) and beryllium sensitization (BeS) demonstrated significantly greater cell surface CD16 (encoded by the FCGR3A gene) than controls. We hypothesized that these differences were related to polymorphisms in the FCGR3A gene. This study was to determine the association between FCGR3A polymorphisms in CBD, BeS versus controls as well as clinical data, providing potential information about disease pathogenesis, risk, and activity. A total of 189 CBD/154 BeS/150 controls (92 Be-exposed non-diseased and 58 healthy controls) were included in this study. Sequence-specific primers polymerase chain reaction (PCR-SSP) was used to determine FCGR3A 158V/F polymorphisms. We found significantly higher frequencies of the 158V allele (OR: 1.60 (CI: 1.17-2.19), p = 0.004) and 158VV homozygotes (OR: 2.97 (CI: 1.48-5.97) p = 0.007) in CBD versus controls. No differences were found in the frequencies of FCGR3A alleles or genotypes between BeS versus controls and CBD versus BeS. Average changes in exercise testing maximum workload (Wlm), maximum oxygen consumption (VOm), and diffusion capacity of carbon monoxide (DLCO) demonstrated greater decline over time in those CBD cases with the 158VV gene, modeled between 10 and 40 years from first beryllium exposure. The FCGR3A V158F polymorphism is associated with CBD compared to BeS and controls and may impact lung function in CBD.
Topics: Adult; Aged; Alleles; Berylliosis; Beryllium; Chronic Disease; Female; Genotype; Humans; Lung; Male; Middle Aged; Polymorphism, Genetic; Receptors, IgG; Risk Factors
PubMed: 30245507
DOI: 10.1038/s41435-018-0046-8