Systemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.

[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.

Disciplines :

Cardiovascular & respiratory systems

Author, co-author :

Stolz, Daiana

Leeming, Diana Julie

Edfort Kristensen, Jacob Hull

Karsdal, Morten A.

Boersma, Wim

Louis, Renaud ; Université de Liège > Département des sciences cliniques > Pneumologie - Allergologie

Milenkovic, Branislava

Kostikas, Konstantinos

Blasi, Francesco

Aerts, Joachim

More authors (9 more)

Language :

English

Title :

Systemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.

Publication date :

26 August 2016

Journal title :

CHEST

ISSN :

0012-3692

eISSN :

1931-3543

Publisher :

American College of Chest Physicians, Northbrook, United States - Illinois

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.sciencedirect.com/science/article/pii/S0012369216578349

Commentary :

Available on ORBi :

since 30 September 2016

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