Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort

Sarah Rank Rønnow*, Lasse Løcke Langholm, Jannie Marie Bülow Sand, Jeppe Thorlacius-Ussing, Diana Julie Leeming, Tina Manon-Jensen, Ruth Tal-Singer, Bruce E. Miller, Morten Asser Karsdal, Jørgen Vestbo

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Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer4064
TidsskriftScientific Reports
Vol/bind9
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - 1. mar. 2019

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Rønnow, S. R., Langholm, L. L., Sand, J. M. B., Thorlacius-Ussing, J., Leeming, D. J., Manon-Jensen, T., Tal-Singer, R., Miller, B. E., Karsdal, M. A., & Vestbo, J. (2019). Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort. Scientific Reports, 9(1), [4064]. https://doi.org/10.1038/s41598-019-40785-2