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Toxicol Lett 2022 May 12;361:64-71. Epub 2022 Apr 12.

Clinical Unit of Occupational Medicine, University of Trieste, Italy.

Dermal exposure to hazardous substances such as chemicals, toxics, metallic items and other contaminants may present substantial danger for health. Beryllium (Be) is a hazardous metal, especially when inhaled and/or in direct contact with the skin, associated with chronic beryllium disease (CBD) and Be sensitization (BeS). The objective of this study was to investigate the percutaneous penetration of beryllium and copper contained in metallic items as eyeglass temple tips (specifically BrushCAST® Copper Beryllium Casting Alloys containing Be 0. Read More

J Immunol 2022 04;208(8):1835-1843

Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; and

Sarcoidosis and chronic beryllium disease are noninfectious lung diseases that are characterized by the presence of noncaseating granulomatous inflammation. Chronic beryllium disease is caused by occupational exposure to beryllium containing particles, whereas the etiology of sarcoidosis is not known. Genetic susceptibility for both diseases is associated with particular MHC class II alleles, and CD4 T cells are implicated in their pathogenesis. Read More

Internist (Berl) 2022 May 9;63(5):557-565. Epub 2022 Apr 9.

Klinik für Pneumologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Killianstraße 5, 79106, Freiburg, Deutschland.

Sarcoidosis and berylliosis (chronic beryllium disease, CBD) are granulomatous diseases and are phenocopies which cannot be differentiated based on the clinical presentation. Whereas for sarcoidosis the eliciting agent is unknown, for berylliosis an exposure to beryllium (mostly as occupational exposure) can be confirmed that therefore induces a sensitization against beryllium. The diagnosis is generally made in patients with a typical clinical presentation, the histological proof of a non-necrotizing granuloma and the exclusion of other diseases causing granulomas. Read More

Toxicol Ind Health 2022 Feb 1;38(2):63-69. Epub 2022 Mar 1.

114866Integral Consulting Inc., Portland, ME, USA.

Workers involved in crushing, milling, screening, and bagging of mica scrap are at increased risk to develop pneumoconiosis, a progressive material overloading of the lung that can lead to fibrosis and, in the later stages, to dyspnea. Pneumoconiosis is only seen after 10-20 years of respiratory mica exposure, and it can have a latency period of up to 40 years-today's cases date back to exposures during the second half of the 20 century. An occupational lifetime exposure level of 3 mg/m respirable mica dust has been considered to present no risk of pneumoconiosis since 1951 when the American Conference of Governmental Industrial Hygienists (ACGIH) established a 20 million particles per cubic foot (mppcf) (3. Read More

Occup Environ Med 2022 02 17;79(2):120-126. Epub 2021 Sep 17.

Department of Medicine, National Jewish Health, Denver, Colorado, USA

Objectives: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD.

Methods: Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Read More

Respir Med 2021 10 5;187:106390. Epub 2021 Apr 5.

Department of Medicine, University of Colorado, Aurora, CO, USA; Department of Medicine, National Jewish Health, Denver, CO, USA. Electronic address:

Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes. Read More

Curr Opin Pulm Med 2021 09;27(5):430-438

Interstitial Lung Diseases Centre of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein.

Purpose Of Review: Previous studies mainly described a role for organic agents as possible triggers for sarcoidosis. In this review, we address recent studies suggesting a possible role for inorganic elements, such as metals or silica in sarcoidosis pathogenesis.

Recent Findings: Several epidemiological papers suggest that inorganic agents, either by environmental exposures or occupational activities, could trigger sarcoidosis. Read More

Chest 2021 06;159(6):2508-2509

Materion Corp Ringgold standard institution-Medical, Mayfield Heights, OH.

Mediators Inflamm 2021 6;2021:8845966. Epub 2021 May 6.

Department of Pulmonary Medicine, Erasmus University Medical Center (Erasmus MC), Dr. Molewaterplein 50, 3015 GE Rotterdam, Netherlands.

Objective: To study airway pathophysiology and the role of dendritic cells (DCs) and IL-17 receptor (IL-17R) signals in a mouse model for CBD.

Methods: Here, we present a CBD mouse model in which mice were exposed to beryllium during three weeks. We also exposed IL-17R-deficient mice and mice in which DCs were depleted. Read More

Int J Radiat Biol 2022 21;98(4):722-749. Epub 2021 Jun 21.

Easterly Scientific, Knoxville, TN, USA.

Background: During World War II (WWII), the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed 'The Gadget' that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL). Read More

J Clin Invest 2021 05;131(9)

Recognition of self-peptides in association with distinct HLA class II alleles by autoreactive CD4+ T cells is central for loss of immunological tolerance leading to autoimmune disease. However, identifying immunodominant self-peptides and characterizing autoreactive T cells is challenging. In this issue of the JCI, Falta et al. Read More

Arch Pathol Lab Med 2022 01;146(2):233-251

From the Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, New York.

Context.—: Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large. Their diagnosis by pathologists is particularly challenging because of their nonspecificity. Read More

Respir Res 2021 Apr 16;22(1):107. Epub 2021 Apr 16.

Department of Pneumology, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.

Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Read More

J Clin Invest 2021 05;131(9)

Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Discovering dominant epitopes for T cells, particularly CD4+ T cells, in human immune-mediated diseases remains a significant challenge. Here, we used bronchoalveolar lavage (BAL) cells from HLA-DP2-expressing patients with chronic beryllium disease (CBD), a debilitating granulomatous lung disorder characterized by accumulations of beryllium-specific (Be-specific) CD4+ T cells in the lung. We discovered lung-resident CD4+ T cells that expressed a disease-specific public CDR3β T cell receptor motif and were specific to Be-modified self-peptides derived from C-C motif ligand 4 (CCL4) and CCL3. Read More

Medicina (Kaunas) 2020 Nov 22;56(11). Epub 2020 Nov 22.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.

Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in CBD have occasionally been reported in exposure to dusts of other metals. However, reports describing the clinical, radiographic, and pathological findings in conditions other than beryllium-induced granulomatous lung diseases, and detailed information on mineralogical analyses of metal dusts, are limited. Read More

Cent Eur J Public Health 2020 Sep;28(3):198-201

Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Beryllium has an impact on the human health of professionally or non-occupationally exposed people. Current evidence suggests that beryllium acts as a hapten with limited antigenic properties and is presented by antigen presenting cells to CD4 T cells, which possess specific antigen receptors. The immunological changes in humoral immunoreactivity were considered biomarkers of beryllium exposure. Read More

Chest 2021 03 12;159(3):1084-1093. Epub 2020 Sep 12.

Department of Pneumology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Background: Chronic beryllium disease (CBD), a granulomatous disease with similarities to sarcoidosis, arises only in individuals exposed to beryllium. Inhaled beryllium can elicit a T-cell-dominated alveolitis leading nonnecrotizing granulomata. CBD can be distinguished from sarcoidosis by demonstrating beryllium sensitization in a lymphocyte proliferation test. Read More

Occup Environ Med 2020 11 28;77(11):790-794. Epub 2020 Aug 28.

Respiratory Health Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA

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. Read More

Sangyo Eiseigaku Zasshi 2021 Mar 12;63(2):31-42. Epub 2020 Aug 12.

National Institute of Occupational Safety and Health.

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. Read More

Chest 2020 12 6;158(6):2458-2466. Epub 2020 Aug 6.

Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO.

Beryllium exposure remains an ongoing occupational health concern for workers worldwide. Since the initial Occupational Safety and Health Administration (OSHA) ruling on a permissible exposure limit (PEL) for beryllium in 1971, our understanding of the risks of beryllium sensitization and chronic beryllium disease (CBD) has evolved substantially. A new OSHA ruling released in early 2017 and implemented in late 2018 reduced the PEL for beryllium, increased requirements for medical screening and monitoring, and may ultimately enhance worker protection. Read More

Am J Respir Crit Care Med 2020 10;202(7):1013-1023

Department of Biomedical Research.

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. Read More

Rev Mal Respir 2020 May 9;37(5):364-368. Epub 2020 Apr 9.

Service de pneumologie, centre de compétences des maladies pulmonaires rares de la région Centre, hôpital Bretonneau, CHRU de Tours, Tours, France; CEPR InsermU1100, Université Francois-Rabelais de Tours, Tours, France. Electronic address:

Introduction: The epidemiology of chronic beryllium disease (CBD) in France is poorly understood. The aim of this study was to determine the number of prevalent cases of CBD in France between 2010 and 2014.

Methods: We conducted a national survey using a specific questionnaire distributed by the professional pathology services. Read More

Front Immunol 2020 18;11:474. Epub 2020 Mar 18.

Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

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. Read More

JCI Insight 2020 05 7;5(9). Epub 2020 May 7.

Division of Allergy, Asthma and Clinical Immunology, Department of Medicine.

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. Read More

Arch Bronconeumol (Engl Ed) 2020 Jul 31;56(7):470-471. Epub 2020 Mar 31.

Servicio de Inmunología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España.

J Occup Environ Med 2020 01;62(1):64-73

Department of Public Health and Preventive Medicine, Universitas Sebelas Maret, Surakarta, Indonesia (Dr Widyaningsih); Department of Medicine (Dr Rosenman, Ms Reilly, Dr Wang); Department of Epidemiology and Biostatistics (Dr Pathak, Dr Gardiner), Michigan State University, East Lansing, Michigan; Department of Environmental Health, University of Cincinnati, Cincinnati (Dr Rice); Department of Pathology and Laboratory Medicine (Dr Monos); Department of Medicine (Dr Rossman), University of Pennsylvania, Philadelphia.

Objective: To evaluate interaction of HLA-DPβ1 and DRβ1 polymorphisms with metrics of beryllium exposure, in the development of beryllium sensitization (BeS) and chronic beryllium disease (CBD).

Methods: A matched case-control study of 61 CBD, 41 BeS, and 259 controls from two beryllium-processing facilities.

Results: BES and CBD were significantly associated with presence of DPβE69. Read More

Chemistry 2019 Dec 8;25(71):16170. Epub 2019 Nov 8.

Anorganische Chemie, Nachwuchsgruppe Berylliumchemie, Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35032, Marburg, Germany.

Invited for the cover of this issue is the group of Magnus R. Buchner at Philipps-Universität Marburg. The image depicts a piece of beryllium decomposing sugar cubes. Read More

Ann Work Expo Health 2019 10;63(8):856-869

National Institute for Occupational Safety and Health, Respiratory Health Division, Morgantown, WV, USA.

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. Read More

Chemistry 2019 Dec 8;25(71):16257-16269. Epub 2019 Nov 8.

Anorganische Chemie, Nachwuchsgruppe Berylliumchemie, Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35032, Marburg, Germany.

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. Read More

Pan Afr Med J 2018 9;31:95. Epub 2018 Oct 9.

Medical Intensive Care Unit, Abderrahmen Mami Hospital, Ariana 2080, Tunisia.

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. Read More