Tina Manon-Jensen1, Lasse L Langholm2, Sarah Rank Rønnow3, Morten Asser Karsdal4, Ruth Tal-Singer5, Jørgen Vestbo6, Diana Julie Leeming4, Bruce E Miller5, Jannie Marie Bülow Sand4. 1. Nordic Bioscience A/S, Herlev, Denmark. Electronic address: TMJ@nordicbio.com. 2. Nordic Bioscience A/S, Herlev, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Biomedical Sciences, Copenhagen, Denmark. 3. Nordic Bioscience A/S, Herlev, Denmark; University of Southern Denmark, The Faculty of Health Science, Odense, Denmark. 4. Nordic Bioscience A/S, Herlev, Denmark. 5. GSK R&D, Collegeville, PA, USA. 6. Division of Infection Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, England, UK.
Abstract
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.
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.
Authors: Jannie M B Sand; Sarah R Rønnow; Lasse L Langholm; Morten A Karsdal; Tina Manon-Jensen; Ruth Tal-Singer; Bruce E Miller; Jørgen Vestbo; Diana J Leeming Journal: Respir Med Date: 2020-10-02 Impact factor: 3.415
Authors: Qingling Li; Weng Wong; Andrew Birnberg; Arindam Chakrabarti; Xiaoying Yang; David F Choy; Julie Olsson; Erik Verschueren; Margaret Neighbors; Wendy Sandoval; Carrie M Rosenberger; Michele A Grimbaldeston; Gaik W Tew Journal: BMC Pulm Med Date: 2021-09-23 Impact factor: 3.317
Authors: Peter Kamstrup; Jannie Marie Bülow Sand; Charlotte Suppli Ulrik; Julie Janner; Christian Philip Rønn; Sarah Rank Rønnow; Diana Julie Leeming; Sidse Graff Jensen; Torgny Wilcke; Alexander G Mathioudakis; Marc Miravitlles; Therese Lapperre; Elisabeth Bendstrup; Ruth Frikke-Schmidt; Daniel D Murray; Theis Itenov; Apostolos Bossios; Susanne Dam Nielsen; Jørgen Vestbo; Tor Biering-Sørensen; Morten Karsdal; Jens-Ulrik Jensen; Pradeesh Sivapalan Journal: Biomedicines Date: 2022-08-19
Authors: Lasse L Langholm; Sarah Rank Rønnow; Jannie M B Sand; Diana Julie Leeming; Ruth Tal-Singer; Bruce E Miller; Jørgen Vestbo; Morten A Karsdal; Tina Manon-Jensen Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-03-09