Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort. / Rønnow, Sarah Rank; Langholm, Lasse Løcke; Sand, Jannie Marie Bülow; Thorlacius-Ussing, Jeppe; Leeming, Diana Julie; Manon-Jensen, Tina; Tal-Singer, Ruth; Miller, Bruce E.; Karsdal, Morten Asser; Vestbo, Jørgen.
In: Scientific Reports, Vol. 9, No. 1, 4064, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort
AU - Rønnow, Sarah Rank
AU - Langholm, Lasse Løcke
AU - Sand, Jannie Marie Bülow
AU - Thorlacius-Ussing, Jeppe
AU - Leeming, Diana Julie
AU - Manon-Jensen, Tina
AU - Tal-Singer, Ruth
AU - Miller, Bruce E.
AU - Karsdal, Morten Asser
AU - Vestbo, Jørgen
PY - 2019
Y1 - 2019
N2 - Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an essential structural protein of the lungs. In this study, we investigated whether elastin degradation products generated by the enzymes proteinase 3, cathepsin G, neutrophil elastase, MMP7 or MMP9/12 were prognostic biomarkers for COPD-related outcomes. The elastin degradome was assessed in a subpopulation (n = 1307) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort with 3 years of clinical follow-up. Elastin degraded by proteinase 3 could distinguish between COPD participants and non-smoking controls (p = 0.0006). A total of 30 participants (3%) died over the 3 years of observation. After adjusting for confounders, plasma levels of elastin degraded by proteinase 3 and cathepsin G were independently associated with mortality outcome with a hazard ratio per 1 SD of 1.49 (95%CI 1.24–1.80, p < 0.0001) and 1.31 (95%CI 1.10–1.57, p = 0.0029), respectively. Assessing the elastin degradome demonstrated that specific elastin degradation fragments have potential utility as biomarkers identifying subtypes of COPD patients at risk of poor prognosis and supports further exploration in confirmatory studies.
AB - Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an essential structural protein of the lungs. In this study, we investigated whether elastin degradation products generated by the enzymes proteinase 3, cathepsin G, neutrophil elastase, MMP7 or MMP9/12 were prognostic biomarkers for COPD-related outcomes. The elastin degradome was assessed in a subpopulation (n = 1307) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort with 3 years of clinical follow-up. Elastin degraded by proteinase 3 could distinguish between COPD participants and non-smoking controls (p = 0.0006). A total of 30 participants (3%) died over the 3 years of observation. After adjusting for confounders, plasma levels of elastin degraded by proteinase 3 and cathepsin G were independently associated with mortality outcome with a hazard ratio per 1 SD of 1.49 (95%CI 1.24–1.80, p < 0.0001) and 1.31 (95%CI 1.10–1.57, p = 0.0029), respectively. Assessing the elastin degradome demonstrated that specific elastin degradation fragments have potential utility as biomarkers identifying subtypes of COPD patients at risk of poor prognosis and supports further exploration in confirmatory studies.
U2 - 10.1038/s41598-019-40785-2
DO - 10.1038/s41598-019-40785-2
M3 - Journal article
C2 - 30858579
AN - SCOPUS:85062765628
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 4064
ER -
ID: 241157040