TY - JOUR T1 - A combination of biomarkers for fibrinolysis and basement membrane destruction predicts mortality in the ECLIPSE COPD cohort JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.4716 VL - 56 IS - suppl 64 SP - 4716 AU - Jannie Sand AU - Sarah R Rønnow AU - Lasse Langholm AU - Morten A Karsdal AU - Tina Manon-Jensen AU - Ruth Tal-Singer AU - Bruce E Miller AU - Jørgen Vestbo AU - Diana J Leeming Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/4716.abstract N2 - Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state, intra-alveolar accumulation of fibrin and basement membrane destruction. The aim of this study was to investigate if serological assessment of these processes were associated with COPD progression.Methods: Plasmin-mediated degradation of cross-linked fibrin (X-FIB), an end-product of fibrinogen, and MMP-mediated degradation of type IV collagen (C4Ma3) were assessed in plasma of 984 COPD subjects from the ECLIPSE cohort. Biomarker data were dichotomized into high vs low by ROC analysis. Cox proportional hazards regression assessed predictive value of the biomarkers alone and in combination for all-cause mortality after 2 years.Results: High levels of plasma X-FIB and C4Ma3 were associated with increased risk of mortality as compared with low levels, with hazard ratios of 4.88 (95% CI 2.28-10.47) and 4.68 (1.40-15.71), respectively. The combination of markers of fibrin cross-linking and collagen IV degradation increased the hazard ratio to 7.35 (3.48-15.55). Additionally, X-FIB was associated with emphysema while C4Ma3 was associated with acute exacerbations.Conclusions: Serological assessments of lung remodeling related to the abnormal epithelial repair in COPD are associated with a poor prognosis. The combination of two different aspects of COPD pathology, elevated wound healing and basement membrane destruction, may improve prediction.Method: GSK (ECLIPSE; SCO104960, NCT00292552); The Danish Agency for Science, Technology, and Innovation; The Danish Research Foundation; NIHR Manchester Biomedical Research Centre.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4716.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -