TY - JOUR
T1 - Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD
AU - Stolz, Daiana
AU - Leeming, Diana Julie
AU - Kristensen, Jacob Hull Edfort
AU - Karsdal, Morten A.
AU - Boersma, Wim
AU - Louis, Renaud
AU - Milenkovic, Branislava
AU - Kostikas, Konstantinos
AU - Blasi, Francesco
AU - Aerts, Joachim
AU - Sand, Jannie M. B.
AU - Wouters, Emiel F. M.
AU - Rohde, Gernot
AU - Prat, Cristina
AU - Torres, Antoni
AU - Welte, Tobias
AU - Roth, Michael
AU - Papakonstantinou, Eleni
AU - Tamm, Michael
PY - 2017/1
Y1 - 2017/1
N2 - 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), proforms 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.
AB - 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), proforms 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.
KW - acute exacerbations of COPD
KW - collagen
KW - COPD
KW - elastin
KW - extracellular matrix molecules
KW - OBSTRUCTIVE PULMONARY-DISEASE
KW - EXTRACELLULAR-MATRIX
KW - ACUTE EXACERBATIONS
KW - LIVER FIBROSIS
KW - LUNG-FUNCTION
KW - DEGRADATION
KW - AIRWAY
KW - INFLAMMATION
U2 - 10.1016/j.chest.2016.08.1440
DO - 10.1016/j.chest.2016.08.1440
M3 - Article
C2 - 27575358
SN - 0012-3692
VL - 151
SP - 47
EP - 59
JO - Chest
JF - Chest
IS - 1
ER -