Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease

Abstract Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effect...

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Autores principales:	Dong-Hyun Joo, Kyoung-Hee Lee, Chang-Hoon Lee, Jisu Woo, Jiyeon Kim, Seoung Ju Park, Chin Kook Rhee, Won-Yeon Lee, Dongil Park, Jae Seung Lee, Ki-Suck Jung, Kwang Ha Yoo, Chul-Gyu Yoo
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Chronic obstructive pulmonary disease Developmental endothelial locus-1 Disease progression Biomarkers Animal disease models Diseases of the respiratory system RC705-779
Acceso en línea:	https://doaj.org/article/00b2ae17ff3142a9a1a5eaeb6942b41a
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spelling	oai:doaj.org-article:00b2ae17ff3142a9a1a5eaeb6942b41a2021-11-21T12:32:01ZDevelopmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease10.1186/s12931-021-01878-71465-993Xhttps://doaj.org/article/00b2ae17ff3142a9a1a5eaeb6942b41a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12931-021-01878-7https://doaj.org/toc/1465-993XAbstract Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.Dong-Hyun JooKyoung-Hee LeeChang-Hoon LeeJisu WooJiyeon KimSeoung Ju ParkChin Kook RheeWon-Yeon LeeDongil ParkJae Seung LeeKi-Suck JungKwang Ha YooChul-Gyu YooBMCarticleChronic obstructive pulmonary diseaseDevelopmental endothelial locus-1Disease progressionBiomarkersAnimal disease modelsDiseases of the respiratory systemRC705-779ENRespiratory Research, Vol 22, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chronic obstructive pulmonary disease Developmental endothelial locus-1 Disease progression Biomarkers Animal disease models Diseases of the respiratory system RC705-779
spellingShingle	Chronic obstructive pulmonary disease Developmental endothelial locus-1 Disease progression Biomarkers Animal disease models Diseases of the respiratory system RC705-779 Dong-Hyun Joo Kyoung-Hee Lee Chang-Hoon Lee Jisu Woo Jiyeon Kim Seoung Ju Park Chin Kook Rhee Won-Yeon Lee Dongil Park Jae Seung Lee Ki-Suck Jung Kwang Ha Yoo Chul-Gyu Yoo Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
description	Abstract Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.
format	article
author	Dong-Hyun Joo Kyoung-Hee Lee Chang-Hoon Lee Jisu Woo Jiyeon Kim Seoung Ju Park Chin Kook Rhee Won-Yeon Lee Dongil Park Jae Seung Lee Ki-Suck Jung Kwang Ha Yoo Chul-Gyu Yoo
author_facet	Dong-Hyun Joo Kyoung-Hee Lee Chang-Hoon Lee Jisu Woo Jiyeon Kim Seoung Ju Park Chin Kook Rhee Won-Yeon Lee Dongil Park Jae Seung Lee Ki-Suck Jung Kwang Ha Yoo Chul-Gyu Yoo
author_sort	Dong-Hyun Joo
title	Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
title_short	Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
title_full	Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
title_fullStr	Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
title_full_unstemmed	Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
title_sort	developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease
publisher	BMC
publishDate	2021
url	https://doaj.org/article/00b2ae17ff3142a9a1a5eaeb6942b41a
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Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease

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