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Respiratory Research
Published in: Respiratory Research 1/2016

Open Access 01-12-2016 | Research

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD – results from the ECLIPSE study

Authors: Jannie M. B. Sand, Diana J. Leeming, Inger Byrjalsen, Asger R. Bihlet, Peter Lange, Ruth Tal-Singer, Bruce E. Miller, Morten A. Karsdal, Jørgen Vestbo

Published in: Respiratory Research | Issue 1/2016

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Abstract

Background

There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling.

Methods

Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. Validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used. Multivariate models were used to assess the prognostic value of these biomarkers.

Results

Thirty subjects (3.0 %) died during follow-up. Non-survivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers. All collagen biomarkers were significantly elevated in non-survivors compared to survivors. Mortality risk was significantly increased for subjects with collagen remodeling biomarkers in the upper quartile, especially for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 % confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant confounders.

Conclusions

Serological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD.

Trial registration

NCT00292552, GSK Study No. SCO104960.
Appendix
Available only for authorised users
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Metadata
Title
High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD – results from the ECLIPSE study
Authors
Jannie M. B. Sand
Diana J. Leeming
Inger Byrjalsen
Asger R. Bihlet
Peter Lange
Ruth Tal-Singer
Bruce E. Miller
Morten A. Karsdal
Jørgen Vestbo
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2016
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-016-0440-6

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