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


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Article Info

DATE

2021-11-20

AUTHORS

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

ABSTRACT

BackgroundDespite 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.ObjectiveTo elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation.MethodsCigarette 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.ResultsIn 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).ConclusionLow 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. More... »

PAGES

297

Journal

TITLE

Respiratory Research

ISSUE

1

VOLUME

22

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12931-021-01878-7

DOI

http://dx.doi.org/10.1186/s12931-021-01878-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1142712151

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34801026


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27 schema:description BackgroundDespite 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.ObjectiveTo elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation.MethodsCigarette 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.ResultsIn 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).ConclusionLow 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.
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33 schema:keywords BackgroundDespite
34 C57BL/6 mice
35 COPD acute exacerbation
36 COPD biomarkers
37 COPD development
38 COPD exacerbations
39 CSE
40 KO
41 ObjectiveTo
42 ResultsIn
43 acute COPD exacerbation
44 acute exacerbation
45 acute exacerbation risk
46 analysis
47 anti-inflammatory effects
48 association
49 beneficial effects
50 binomial regression analysis
51 biomarkers
52 biomarkers of COPD
53 blood biomarkers
54 burden
55 chronic obstructive pulmonary disease
56 cohort
57 degree
58 degree of emphysema
59 development
60 developmental endothelial locus-1
61 disease
62 disease burden
63 effect
64 emphysema
65 exacerbation
66 exacerbation risk
67 extract
68 high disease burden
69 highest quartile
70 incidence
71 intercept
72 knockout C57BL/6 mice
73 levels
74 linear intercept
75 locus 1
76 log level
77 lowest quartile
78 lung sections
79 mean linear intercept
80 mice
81 negative binomial regression analysis
82 non-COPD participants
83 obstructive pulmonary disease
84 ongoing prospective cohort
85 participants
86 pathogenesis
87 patients
88 potential biomarkers
89 prospective cohort
90 pulmonary disease
91 quartile
92 regression analysis
93 risk
94 role
95 saline
96 sections
97 smoke extract
98 study
99 subsequent acute exacerbation
100 terms
101 terms of pathogenesis
102 useful biomarker
103 vivo studies
104 years
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