Reference : Systemic biomarkers of collagen and elastin turnover are associated with clinically r...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Systemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.
Stolz, Daiana [> >]
Leeming, Diana Julie [> >]
Edfort Kristensen, Jacob Hull [> >]
Karsdal, Morten A. [> >]
Boersma, Wim [> >]
Louis, Renaud mailto [Université de Liège > Département des sciences cliniques > Pneumologie - Allergologie >]
Milenkovic, Branislava [> >]
Kostikas, Konstantinos [> >]
Blasi, Francesco [> >]
Aerts, Joachim [> >]
Sand, Jannie M. B. [> >]
Wouters, Emiel Fm [> >]
Rohde, Gernot [> >]
Prat, Cristina [> >]
Torres, Antoni [> >]
Welte, Tobias [> >]
Roth, Michael [> >]
Papakonstantinou, Eleni [> >]
Tamm, Michael [> >]
American College of Chest Physicians
Yes (verified by ORBi)
[en] BACKGROUND: Extracellular matrix remodeling (ECM) of the lung tissue releases protein fragments into the blood, where they may be detected as serological surrogate markers of disease activity in chronic obstructive pulmonary disease (COPD). We aimed to assess the association of ECM turnover with severity and outcome of COPD. METHODS: In a prospective, observational, multicenter study including 506 patients with COPD, GOLD grades II-IV, we analyzed serum samples at stable state, exacerbation and 4 weeks after exacerbation, for a panel of 5 novel neo-epitopes including fragments of collagen type-III (C3M) and type-VI (C6M), pro-forms of collagen type-III (Pro-C3) and type-VI (Pro-C6) and neutrophil elastase-generated fragments of elastin (EL-NE) by ELISA. These neo-epitopes were also measured at stable state in a derivation cohort including 100 COPD patients. RESULTS: Serum levels of C3M, C6M, Pro-C3, Pro-C6 and EL-NE were associated with lung function. Patients with the lowest levels of Pro-C3 and Pro-C6 had more severe airflow limitation, hyperinflation, air trapping, and emphysema. Degradation of collagen type-III and -VI was associated with dyspnea. All ECM biomarkers, except Pro-C6, were increased at exacerbation as compared to stable state but, except EL-NE, did not differ between stable state and exacerbation follow-up in the crude and adjusted analyses. In Cox regression adjusted analyses, Pro-C3 was associated with a shorter time to exacerbation (HR 0.72[0.59-0.89] p=0.002) and Pro-C6 with survival (HR 2.09[1.18-3.71], p=0.011). CONCLUSIONS: Serum biomarkers of ECM turnover are significantly associated with disease severity and clinically relevant outcomes in COPD.
Copyright (c) 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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