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Archives of Pathology & Laboratory... Jan 2022Because granulomas are represented in almost every disease category, the number of clinically and pathologically important granulomatous pulmonary diseases is large.... (Review)
Review
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. A specific diagnosis can be achieved only when a granuloma-inciting agent(s) (eg, acid-fast bacilli, fungi, foreign bodies, etc) are identified microscopically or by culture; this does not occur in most cases. Furthermore, a specific diagnosis cannot be reached in a high percentage of cases. Although sarcoidosis and infectious diseases account for approximately half of pulmonary granulomatous diseases worldwide, there is significant geographic variation in their prevalence.
OBJECTIVES.—
To present updated information to serve as a guide to pathologic diagnosis of pulmonary granulomatous diseases, to address some commonly held misconceptions and to stress the importance of multidisciplinary coordination. Presentation of basic aspects of granulomas is followed by discussion of specific disease entities, such as tuberculous and nontuberculous Mycobacterial infections, fungal, bacterial, and parasitic infections, sarcoidosis, necrotizing sarcoid granulomatosis, berylliosis, hypersensitivity pneumonitis, hot tub lung, rheumatoid nodule, bronchocentric granulomatosis, aspirated, inhaled, and embolized foreign bodies, drug-induced granulomas, chronic granulomatous disease, common variable immunodeficiency, and granulomatous lesions associated with various types of cancer.
DATA SOURCES.—
Review of pertinent medical literature using the PubMed search engine and the author's practical experience.
CONCLUSIONS.—
Although the diagnosis of granulomatous lung diseases continues to present significant challenges to pathologists, the information presented in this review can be helpful in overcoming them. The importance of multidisciplinary coordination in cases where morphologic diagnosis is not possible cannot be overstated.
Topics: Alveolitis, Extrinsic Allergic; Granuloma; Humans; Lung; Lung Diseases; Sarcoidosis
PubMed: 33905479
DOI: 10.5858/arpa.2020-0543-RA -
CMAJ : Canadian Medical Association... Feb 2024
Topics: Humans; Middle Aged; Berylliosis; Metal Workers
PubMed: 38346777
DOI: 10.1503/cmaj.221680-f -
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 -
International Journal of Molecular... Nov 2022Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in... (Review)
Review
Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.
Topics: Cathepsin K; Collagen Type I; Bone and Bones; Cysteine Proteases
PubMed: 36430239
DOI: 10.3390/ijms232213762 -
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 -
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 -
CMAJ : Canadian Medical Association... Dec 2023
Topics: Humans; Middle Aged; Berylliosis; Metal Workers
PubMed: 38049163
DOI: 10.1503/cmaj.221680