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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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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.
Author(s)
이재승Chang-Hoon LeeChin Kook RheeChul-Gyu YooDong-Hyun JooDongil ParkJisu WooJiyeon KimKi-Suck JungKwang Ha YooKyoung-Hee LeeSeoung Ju ParkWon-Yeon Lee
Issued Date
2021
Type
Article
Keyword
Animal disease modelsBiomarkersChronic ovstructive pulmonary diseaseDevelopment and progressionDevelopmental endothelial locus-1Disease progressionEndotheliumLung diseasesObstructiveMedical researchMedicineExperimentalMice
DOI
10.1186/s12931-021-01878-7
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7240
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_00b2ae17ff3142a9a1a5eaeb6942b41a&amp;context=PC&amp;vid=ULSAN&amp;lang=ko_KR&amp;search_scope=default_scope&amp;adaptor=primo_central_multiple_fe&amp;tab=default_tab&amp;query=any,contains,Developmental%20endothelial%20locus-1%20as%20a%20potential%20biomarker%20for%20the%20incidence%20of%20acute%20exacerbation%20in%20patients%20with%20chronic%20obstructive%20pulmonary%20disease&amp;offset=0&amp;pcAvailability=true
Publisher
RESPIRATORY RESEARCH
Location
영국
Language
영어
ISSN
1465-993X
Citation Volume
22
Citation Number
1
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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