Abstract
Background: ECM remodeling of the lung tissue releases protein fragments into the blood, where they may potentially be detected as serological surrogate markers of disease activity in COPD. No ECM biomarkers have yet been associated with progression, mortality or AECOPD. Methods: We prospectively evaluated 638 patients with stable COPD, GOLD II-IV, >10 PY from 8 European countries. The primary outcome of the study was exacerbation and death. Median observation time was 24 months. Serum levels of MMP-generated fragment of type III and type VI collagen (C3M, C6M), type III and VI collagen formation (Pro-C3, Pro-C6) and neutrophil elastase-generated fragment of elastin (EL-NE) were measured at stable state, exacerbation and 4 weeks after AECOPD-FU by ELISA (Nordic Bioscience). Results: Except for Pro-C6, biomarkers increased with disease severity and differed significantly among GOLD stages. Strong associations were found for C3M and C6M with dyspnea and C6M and Pro-C6 with exercise capacity. C3M (p=0.01), C6M (p Conclusions: Biomarkers of ECM turnover are significantly associated with clinical relevant outcomes in COPD.
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