End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort

Tina Manon-Jensen*, Lasse L. Langholm, Sarah Rank Rønnow, Morten Asser Karsdal, Ruth Tal-Singer, Jørgen Vestbo, Diana Julie Leeming, Bruce E. Miller, Jannie Marie Bülow Sand

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review


    Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized that changes in the processing of fibrinogen may provide additional characterization of disease phenotype and COPD progression. Methods: A subpopulation of subjects with COPD, (n = 983) smoker (n = 205) and non-smoker controls (n = 98) were included from The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. Two biomarkers that specifically target the thrombin-mediated conversion of fibrinogen into fibrin (PRO-FIB), and plasmin-mediated degradation of cross-linked fibrin (X–FIB) were measured and compared with fibrinogen measurements. Results: X–FIB had a predictive value for two-year mortality, with an adjusted hazard ratio of 1.48 per SD (n = 980; 95% Cl 1.18–1.84; p < 0.0001), and comparable to the fibrinogen hazard ratio of 1.59 per SD (n = 983; 95% Cl 1.29–1.96; p = 0.0003). X–FIB (p < 0.001), fibrinogen (p < 0.0001) and PRO-FIB (p < 0.05) were significantly elevated in symptomatic COPD (mMRC ≥ 2) as compared to asymptomatic COPD. X–FIB was the only biomarker that was associated with emphysema (p < 0.001), and only plasma fibrinogen (p < 0.05) was associated with exacerbations. Conclusion: There is a need for biomarkers to characterize the heterogeneity of COPD, to continuously improve clinical trial design and to identify disease progressors for efficient health care utilization. Each of three fibrinogen biomarkers studied provide information representing distinct aspects of COPD which may be used to characterize disease endotypes and to assess mortality risk in COPD.

    Original languageEnglish
    Article number105814
    JournalRespiratory Medicine
    Number of pages9
    Publication statusPublished - 1. Nov 2019


    • COPD
    • Emphysema
    • Fibrinogen
    • Mortality
    • X–FIB


    Dive into the research topics of 'End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort'. Together they form a unique fingerprint.

    Cite this