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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      Hepatic Fibrosis Assessed Using Fibrosis-4 Index Is Predictive of All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease

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          Abstract

          Background

          Various comorbidities influence the prognosis of patients with chronic obstructive pulmonary disease (COPD). We investigated if liver fibrosis assessed using fibrosis-4 index (FIB-4) is associated with all-cause mortality in patients with COPD.

          Methods

          We included 756 patients diagnosed with COPD between 2006 and 2010. Medical records were retrospectively reviewed until 2018. FIB-4 was calculated using the following equation: [age (years) × aspartate aminotransferase (IU/L)/(platelet count (10 9/L) × √alanine aminotransferase (IU/L))].

          Results

          From a total of 756 patients, 582 (76.9%) patients were categorized into survivor and 174 (23.1%) into non-survivor groups. The non-survivor group was significantly older with a higher proportion of male, smoker and lower FEV 1/FVC ratio than the survivor group (all P<0.05). Various comorbidities were more frequently observed in the non-survivor group (P<0.05). In addition, the non-survivor group had significantly higher FIB-4 than the survivor group (1.8 vs 1.4, P<0.001). In multivariate analysis, older age (hazard ratio [HR]=1.05), underlying malignancy (HR=2.94), coronary artery occlusive disease (HR=1.58), higher FIB-4 (HR=1.15), and higher GOLD stage (HR=1.26) were significantly associated with the increased risk of all-cause mortality (P<0.05), whereas body mass index (HR=0.95) was independently protective for all-cause mortality (all P<0.05). The high FIB-4 (>1.57) group showed a significantly lower cumulative survival rate than the low FIB-4 (≤1.05) group (P=0.031, Log-rank test). In multivariate regression analysis, higher FIB-4 independently predicted the risk of acute exacerbation (odds ratio=1.08, P=0.034).

          Conclusion

          Higher fibrotic burden assessed using FIB-4 was independently predictive of the increased risk of all-cause mortality and acute exacerbation in patients with COPD.

          Most cited references27

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          COPD as a disease of accelerated lung aging.

          There is increasing evidence for a close relationship between aging and chronic inflammatory diseases. COPD is a chronic inflammatory disease of the lungs, which progresses very slowly and the majority of patients are therefore elderly. We here review the evidence that accelerating aging of lung in response to oxidative stress is involved in the pathogenesis and progression of COPD, particularly emphysema. Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death. This results from a failure of organs to repair DNA damage by oxidative stress (nonprogrammed aging) and from telomere shortening as a result of repeated cell division (programmed aging). During aging, pulmonary function progressively deteriorates and pulmonary inflammation increases, accompanied by structural changes, which are described as senile emphysema. Environmental gases, such as cigarette smoke or other pollutants, may accelerate the aging of lung or worsen aging-related events in lung by defective resolution of inflammation, for example, by reducing antiaging molecules, such as histone deacetylases and sirtuins, and this consequently induces accelerated progression of COPD. Recent studies of the signal transduction mechanisms, such as protein acetylation pathways involved in aging, have identified novel antiaging molecules that may provide a new therapeutic approach to COPD.
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            TGF-β Signaling in Lung Health and Disease

            Transforming growth factor (TGF)-β is an evolutionarily conserved pleiotropic factor that regulates a myriad of biological processes including development, tissue regeneration, immune responses, and tumorigenesis. TGF-β is necessary for lung organogenesis and homeostasis as evidenced by genetically engineered mouse models. TGF-β is crucial for epithelial-mesenchymal interactions during lung branching morphogenesis and alveolarization. Expression and activation of the three TGF-β ligand isoforms in the lungs are temporally and spatially regulated by multiple mechanisms. The lungs are structurally exposed to extrinsic stimuli and pathogens, and are susceptible to inflammation, allergic reactions, and carcinogenesis. Upregulation of TGF-β ligands is observed in major pulmonary diseases, including pulmonary fibrosis, emphysema, bronchial asthma, and lung cancer. TGF-β regulates multiple cellular processes such as growth suppression of epithelial cells, alveolar epithelial cell differentiation, fibroblast activation, and extracellular matrix organization. These effects are closely associated with tissue remodeling in pulmonary fibrosis and emphysema. TGF-β is also central to T cell homeostasis and is deeply involved in asthmatic airway inflammation. TGF-β is the most potent inducer of epithelial-mesenchymal transition in non-small cell lung cancer cells and is pivotal to the development of tumor-promoting microenvironment in the lung cancer tissue. This review summarizes and integrates the current knowledge of TGF-β signaling relevant to lung health and disease.
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              Age-related changes in immune function: effect on airway inflammation.

              Immunosenescence is defined as changes in the innate and adaptive immune response associated with increased age. The clinical consequences of immunosenescence include increased susceptibility to infection, malignancy and autoimmunity, decreased response to vaccination, and impaired wound healing. However, there are several immune alterations that might facilitate persistence of asthma into late adulthood or development of asthma after the age of 50 to 60 years. Asthma in older patients is not uncommon, and this is a growing population as the average lifespan increases. Specific innate changes that might affect severity of asthma in older patients or be involved in the development of late-onset asthma include impaired mucociliary clearance and changes in airway neutrophil, eosinophil, and mast cell numbers and function. Additionally, age-related altered antigen presentation and decreased specific antibody responses might increase the risk of respiratory tract infections. Respiratory tract infections exacerbate asthma in older patients and possibly play a role in the pathogenesis of late-onset asthma. Furthermore, cytokine profiles might be modified with aging, with some investigators suggesting a trend toward T(H)2 cytokine expression. This review examines specific innate and adaptive immune responses affected by aging that might affect the inflammatory response in older adults with asthma. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                17 April 2020
                2020
                : 15
                : 831-839
                Affiliations
                [1 ]Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine , Seoul, Republic of Korea
                [2 ]Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine , Seoul, Republic of Korea
                [3 ]Yonsei Liver Center, Severance Hospital , Seoul, Republic of Korea
                Author notes
                Correspondence: Seung Up Kim Department of Internal Medicine, Yonsei University College of Medicine , 50-1 Yonsei-ro, Seodaemun-gu, Seoul03722, Republic of Korea Email ksukorea@yuhs.ac
                Ji Ye Jung Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine , 50-1 Yonsei-ro, Seodaemun-gu, Seoul03722, Korea Email stopyes@yuhs.ac
                Author information
                http://orcid.org/0000-0001-9656-8482
                http://orcid.org/0000-0003-0820-7615
                http://orcid.org/0000-0003-4542-6841
                http://orcid.org/0000-0002-9658-8050
                http://orcid.org/0000-0003-1589-4142
                Article
                242863
                10.2147/COPD.S242863
                7173842
                44c9b03c-210d-41c7-b569-26bcacf6c611
                © 2020 Yong et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 18 December 2019
                : 30 March 2020
                Page count
                Figures: 2, Tables: 4, References: 36, Pages: 9
                Categories
                Original Research

                Respiratory medicine
                chronic obstructive pulmonary disease,exacerbation,fib-4,liver fibrosis,mortality

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