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Annals of Global Health Jan 2019More than 100 different conditions are grouped under the term interstitial lung disease (ILD). A diagnosis of an ILD primarily relies on a combination of clinical,... (Review)
Review
More than 100 different conditions are grouped under the term interstitial lung disease (ILD). A diagnosis of an ILD primarily relies on a combination of clinical, radiological, and pathological criteria, which should be evaluated by a multidisciplinary team of specialists. Multiple factors, such as environmental and occupational exposures, infections, drugs, radiation, and genetic predisposition have been implicated in the pathogenesis of these conditions. Asbestosis and other pneumoconiosis, hypersensitivity pneumonitis (HP), chronic beryllium disease, and smoking-related ILD are specifically linked to inhalational exposure of environmental agents. The recent Global Burden of Disease Study reported that ILD rank 40th in relation to global years of life lost in 2013, which represents an increase of 86% compared to 1990. Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrotic ILD. A recent study from the United States reported that the incidence and prevalence of IPF are 14.6 per 100,000 person-years and 58.7 per 100,000 persons, respectively. These data suggests that, in large populated areas such as Brazil, Russia, India, and China (the BRIC region), there may be approximately 2 million people living with IPF. However, studies from South America found much lower rates (0.4-1.2 cases per 100,000 per year). Limited access to high-resolution computed tomography and spirometry or to multidisciplinary teams for accurate diagnosis and optimal treatment are common challenges to the management of ILD in developing countries.
Topics: Air Pollution; Alveolitis, Extrinsic Allergic; Asbestos; Connective Tissue Diseases; Developing Countries; Environmental Exposure; Health Services Accessibility; Humans; Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis; Incidence; Lung Diseases, Interstitial; Occupational Exposure; Pneumoconiosis; Prevalence; Sarcoidosis, Pulmonary; Spirometry; Tomography, X-Ray Computed
PubMed: 30741505
DOI: 10.5334/aogh.2414 -
European Respiratory Review : An... Jun 2021Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures... (Review)
Review
Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures and genetic variants, and that they regulate immune and fibrotic processes. In this review, we introduce these concepts with a focus on the study of DNA methylation and histone modifications and discuss how they have been applied to lung disease, and how they can be applied to sarcoidosis. This information has implications for other exposure and immunologically mediated lung diseases, such as chronic beryllium disease, hypersensitivity pneumonitis, and asbestosis.
Topics: DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Humans; Lung Diseases; Sarcoidosis
PubMed: 34168064
DOI: 10.1183/16000617.0076-2021 -
International Journal of Molecular... Oct 2022Experimental liver injury with hepatocelluar necrosis and abnormal liver tests is caused by exposure to heavy metals (HMs) like aluminum, arsenic, beryllium, cadmium,... (Review)
Review
Aluminum, Arsenic, Beryllium, Cadmium, Chromium, Cobalt, Copper, Iron, Lead, Mercury, Molybdenum, Nickel, Platinum, Thallium, Titanium, Vanadium, and Zinc: Molecular Aspects in Experimental Liver Injury.
Experimental liver injury with hepatocelluar necrosis and abnormal liver tests is caused by exposure to heavy metals (HMs) like aluminum, arsenic, beryllium, cadmium, chromium, cobalt, copper, iron, lead, mercury, molybdenum, nickel, platinum, thallium, titanium, vanadium, and zinc. As pollutants, HMs disturb the ecosystem, and as these substances are toxic, they may affect the health of humans and animals. HMs are not biodegradable and may be deposited preferentially in the liver. The use of animal models can help identify molecular and mechanistic steps leading to the injury. HMs commonly initiate hepatocellular overproduction of ROS (reactive oxygen species) due to oxidative stress, resulting in covalent binding of radicals to macromolecular proteins or lipids existing in membranes of subcellular organelles. Liver injury is facilitated by iron via the Fenton reaction, providing ROS, and is triggered if protective antioxidant systems are exhausted. Ferroptosis syn pyroptosis was recently introduced as mechanistic concept in explanations of nickel (Ni) liver injury. NiCl causes increased iron deposition in the liver, upregulation of cyclooxygenase 2 (COX-2) protein and mRNA expression levels, downregulation of glutathione eroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), nuclear receptor coactivator 4 (NCOA4) protein, and mRNA expression levels. Nickel may cause hepatic injury through mitochondrial damage and ferroptosis, defined as mechanism of iron-dependent cell death, similar to glutamate-induced excitotoxicity but likely distinct from apoptosis, necrosis, and autophagy. Under discussion were additional mechanistic concepts of hepatocellular uptake and biliary excretion of mercury in exposed animals. For instance, the organic anion transporter 3 (Oat3) and the multidrug resistance-associated protein 2 (Mrp2) were involved in the hepatic handling of mercury. Mercury treatment modified the expression of Mrp2 and Oat3 as assessed by immunoblotting, partially explaining its impaired biliary excretion. Concomitantly, a decrease in Oat3 abundance in the hepatocyte plasma membranes was observed that limits the hepatic uptake of mercury ions. Most importantly and shown for the first time in liver injury caused by HMs, titanium changed the diversity of gut microbiota and modified their metabolic functions, leading to increased generation of lipopolysaccharides (LPS). As endotoxins, LPS may trigger and perpetuate the liver injury at the level of gut-liver. In sum, mechanistic and molecular steps of experimental liver injury due to HM administration are complex, with ROS as the key promotional compound. However, additional concepts such as iron used in the Fenton reaction, ferroptosis, modification of transporter systems, and endotoxins derived from diversity of intestinal bacteria at the gut-liver level merit further consideration.
Topics: Humans; Animals; Nickel; Zinc; Copper; Cadmium; Cobalt; Vanadium; Molybdenum; Aluminum; Chromium; Arsenic; Titanium; Beryllium; Iron; Platinum; Thallium; Reactive Oxygen Species; Cyclooxygenase 2; Mercury; Antioxidants; Lipopolysaccharides; Ecosystem; Apoferritins; Metals, Heavy; Liver; Environmental Pollutants; Glutathione; Necrosis; Glutamates; Nuclear Receptor Coactivators; Organic Anion Transporters; RNA, Messenger
PubMed: 36293069
DOI: 10.3390/ijms232012213 -
Annual Review of Pharmacology and... Jan 2019Metal exposure is pervasive and not limited to sporadic poisoning events or toxic waste sites. Hundreds of millions of people around the globe are affected by chronic... (Review)
Review
Metal exposure is pervasive and not limited to sporadic poisoning events or toxic waste sites. Hundreds of millions of people around the globe are affected by chronic metal exposure, which is associated with serious health concerns, including cancer, as demonstrated in a variety of studies at the molecular, systemic, and epidemiologic levels. Metal-induced toxicity and carcinogenicity are sophisticated and complex in nature. This review provides a broad context and holistic view of currently available studies on the mechanisms of metal-induced carcinogenesis. Specifically, we focus on the five most prevalent carcinogenic metals, arsenic, nickel, cadmium, chromium, and beryllium, and their potential to drive carcinogenesis in humans. A comprehensive understanding of the mechanisms behind the development of metal-induced cancer can provide valuable insights for therapeutic intervention involving molecular targets in metal-induced carcinogenesis.
Topics: Animals; Carcinogenesis; Environmental Exposure; Humans; Metals; Neoplasms
PubMed: 30625284
DOI: 10.1146/annurev-pharmtox-010818-021031 -
Carcinogenesis Sep 2020Many metals are essential for living organisms, but at higher doses they may be toxic and carcinogenic. Metal exposure occurs mainly in occupational settings and... (Review)
Review
Many metals are essential for living organisms, but at higher doses they may be toxic and carcinogenic. Metal exposure occurs mainly in occupational settings and environmental contaminations in drinking water, air pollution and foods, which can result in serious health problems such as cancer. Arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr) and nickel (Ni) are classified as Group 1 carcinogens by the International Agency for Research on Cancer. This review provides a comprehensive summary of current concepts of the molecular mechanisms of metal-induced carcinogenesis and focusing on a variety of pathways, including genotoxicity, mutagenesis, oxidative stress, epigenetic modifications such as DNA methylation, histone post-translational modification and alteration in microRNA regulation, competition with essential metal ions and cancer-related signaling pathways. This review takes a broader perspective and aims to assist in guiding future research with respect to the prevention and therapy of metal exposure in human diseases including cancer.
Topics: Animals; Carcinogenesis; Carcinogens; Environmental Exposure; Humans; Metals; Neoplasms
PubMed: 32674145
DOI: 10.1093/carcin/bgaa076 -
Annals of the American Thoracic Society Apr 2018Metal-induced hypersensitivity is driven by T-cell sensitization to metal ions. Although numerous metals are associated with the development of diffuse parenchymal lung... (Review)
Review
Metal-induced hypersensitivity is driven by T-cell sensitization to metal ions. Although numerous metals are associated with the development of diffuse parenchymal lung disease, beryllium-induced hypersensitivity is the best-studied to date. This review focuses on the interaction between innate and adaptive immunity that leads to the development of chronic beryllium disease. After beryllium exposure, activation of the innate immune system occurs through the engagement of pattern-recognition receptors. This activation leads to cell death, release of alarmins, and activation and migration of dendritic cells to lung-draining lymph nodes. These events culminate in the development of an adaptive immune response that is characterized by beryllium-specific, T-helper type 1-polarized, CD4 T-cells and granuloma formation in the lung. The unique ability of beryllium to bind to human leukocyte antigen-DP molecules that express a glutamic acid at position 69 of the β-chain alters the charge and conformation of the human leukocyte antigen-DP-peptide complex. These changes induce post-translational modifications that are recognized as non-self. In essence, the ability of beryllium to create neoantigens underlies the genesis of chronic beryllium disease, and demonstrates the similarity between beryllium-induced hypersensitivity and autoimmunity.
Topics: Adaptive Immunity; Autoimmunity; Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Genetic Predisposition to Disease; HLA-DP beta-Chains; Humans; Hypersensitivity; Lung
PubMed: 29676647
DOI: 10.1513/AnnalsATS.201707-573MG -
Occupational and Environmental Medicine Feb 2022Human 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...
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. Lifetime-average beryllium exposure estimates were based on workers' job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity.
RESULTS
Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS.
CONCLUSIONS
Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.
Topics: Berylliosis; Beryllium; Case-Control Studies; Chronic Disease; Female; Genotype; HLA-DP beta-Chains; Humans; Male; Occupational Exposure; Polymorphism, Genetic; Retrospective Studies
PubMed: 34535537
DOI: 10.1136/oemed-2021-107736 -
Journal of Immunology (Baltimore, Md. :... Apr 2022Sarcoidosis and chronic beryllium disease are noninfectious lung diseases that are characterized by the presence of noncaseating granulomatous inflammation. Chronic... (Review)
Review
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. The innate immune system plays a critical role in the initiation of pathogenic CD4 T cell responses as well as the transition to active lung disease and disease progression. In this review, we highlight recent insights into Ag recognition in chronic beryllium disease and sarcoidosis. In addition, we discuss the current understanding of the dynamic interactions between the innate and adaptive immune systems and their impact on disease pathogenesis.
Topics: Adaptive Immunity; Berylliosis; Beryllium; Chronic Disease; Granuloma; Humans; Lung Diseases; Sarcoidosis
PubMed: 35418504
DOI: 10.4049/jimmunol.2101159