Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD.

Chest 2017 Jan 26;151(1):47-59. Epub 2016 Aug 26.

Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital, Basel, Switzerland.

Background: Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was 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 (Global Initiative for Chronic Obstructive Lung Disease grades II to IV), serum samples were analyzed at stable state, exacerbation, and 4 weeks after exacerbation. The analysis comprised a panel of five novel neoepitopes, including fragments of collagen type III (C3M) and collagen 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) according to enzyme-linked immunosorbent assay. These neoepitopes were also measured at stable state in a derivation cohort that included 100 patients with COPD.

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. C3M and C6M were associated with dyspnea. All ECM biomarkers, except Pro-C6, were increased at exacerbation compared with 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 (hazard ratio, 0.72; CI, 0.59-0.89; P = .002) and Pro-C6 with survival (hazard ratio, 2.09; CI, 1.18-3.71; P = .011).

Conclusions: Serum biomarkers of ECM turnover were significantly associated with disease severity and clinically relevant outcomes in patients with COPD.

Trial Registry: No.: ISRCTN99586989; URL: www.controlled-trials.com.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2016.08.1440DOI Listing
January 2017
85 Reads

Publication Analysis

Top Keywords

collagen type
12
stable state
12
type iii
8
relevant outcomes
8
adjusted analyses
8
pro-c3 pro-c6
8
ecm turnover
8
c3m c6m
8
clinically relevant
8
hazard ratio
8
state exacerbation
8
turnover associated
8
associated
5
pro-c6
5
exacerbation
5
fragments elastin
4
elastin el-ne
4
neutrophil elastase-generated
4
type pro-c6
4
pro-c6 neutrophil
4

Altmetric Statistics

Similar Publications