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      International Journal of COPD (submit here)

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      Serum Human Epididymal Protein 4 is Associated with Depressive Symptoms in Patients with Chronic Obstructive Pulmonary Disease

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          Abstract

          Background

          Previous studies have suggested that patients with chronic obstructive pulmonary disease (COPD) have a higher incidence of depression and an increased risk of developing various depression-related complications. We aimed to elucidate the association between the serum human epididymal protein 4 (HE4) level and depressive symptoms in patients with COPD.

          Methods

          The data on 219 participants with COPD from The Irish Longitudinal Study on Ageing (TILDA) were analyzed for the association between serum HE4 levels and depressive symptoms, accounting for relevant confounding factors. All the COPD participants were prospectively followed up for a median period of 48 months. Cox proportional hazards analysis was used to evaluate the predictive value of serum HE4 for predicting depression events in these COPD patients.

          Results

          Multivariate linear regression analysis revealed that serum HE4 was independently associated with the depression score after adjusting for age, sex, BMI, current smoking status, current drinking status, admission systolic and diastolic BP, CVD history and laboratory measurements in patients with COPD at baseline (Sβ= 0.149; 95% CI, 0.069–0.201; P<0.001). Multivariate Cox proportional hazards analysis revealed that serum HE4 (HR=2.216, 95% CI 1.691–5.109, P<0.001) was an independent prognostic factor for depression events in these COPD patients.

          Conclusion

          Our results showed that serum HE4 is significantly and independently associated with depression events. Serum HE4 may enable the early recognition of depressive symptoms among COPD patients.

          Most cited references30

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          The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

          L Radloff (1977)
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            Oxidative stress and redox regulation of lung inflammation in COPD.

            Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kappaB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kappaB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kappaB-alpha kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-kappaB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression. Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity. The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kappaB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.
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              Anxiety and depression in COPD: current understanding, unanswered questions, and research needs.

              Approximately 60 million people in the United States live with one of four chronic conditions: heart disease, diabetes, chronic respiratory disease, and major depression. Anxiety and depression are very common comorbidities in COPD and have significant impact on patients, their families, society, and the course of the disease. We report the proceedings of a multidisciplinary workshop on anxiety and depression in COPD that aimed to shed light on the current understanding of these comorbidities, and outline unanswered questions and areas of future research needs. Estimates of prevalence of anxiety and depression in COPD vary widely but are generally higher than those reported in some other advanced chronic diseases. Untreated and undetected anxiety and depressive symptoms may increase physical disability, morbidity, and health-care utilization. Several patient, physician, and system barriers contribute to the underdiagnosis of these disorders in patients with COPD. While few published studies demonstrate that these disorders associated with COPD respond well to appropriate pharmacologic and nonpharmacologic therapy, only a small proportion of COPD patients with these disorders receive effective treatment. Future research is needed to address the impact, early detection, and management of anxiety and depression in COPD.
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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
                30 December 2020
                2020
                : 15
                : 3417-3422
                Affiliations
                [1 ]Health Management Center, The Second Affiliated Hospital of Nanchang University , Nanchang, 330006, People’s Republic of China
                [2 ]Department of Respiratory, The Second Affiliated Hospital of Nanchang University , Nanchang, Jiangxi 330006, People’s Republic of China
                Author notes
                Correspondence: Wei Wang Department of Respiratory, The Second Affiliated Hospital of Nanchang University , Donghu District, Nanchang City, Jiangxi, People’s Republic of ChinaTel +86 15879853419 Email 748146059@qq.com
                Article
                282214
                10.2147/COPD.S282214
                7779315
                055b34ff-7cdf-4e77-be62-4a60deb31129
                © 2020 Shu and Wang.

                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
                : 15 September 2020
                : 11 December 2020
                Page count
                Figures: 0, Tables: 15, References: 30, Pages: 6
                Categories
                Original Research

                Respiratory medicine
                human epididymis protein 4,chronic obstructive pulmonary disease depressive symptoms,prognostic value

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