title: Plasma Fibrinogen as a Biomarker for Mortality and Hospitalized Exacerbations in People with COPD.
abstract: BACKGROUND
  In 2010 the COPD Foundation established the COPD Biomarkers Qualification Consortium (CBQC) as a partnership between the Foundation, the Food and Drug Administration (FDA), and the pharmaceutical industry to pool publicly-funded and industry data to develop innovative tools to facilitate the development and approval of new therapies for COPD. We present data from the initial project seeking regulatory qualification of fibrinogen as a biomarker for the stratification of COPD patients into clinical trials.
  
  
  METHODS
  This analysis pooled data from 4 publicly-funded studies and 1 industry study into a common database resulting in 6376 individuals with spirometric evidence of COPD. We used a threshold of 350 mg/dL to determinehighvs.lowfibrinogen, and determined the subsequent risk of hospitalizations from exacerbations and death using Cox proportional hazards models.
  
  
  RESULTS
  High fibrinogen levels at baseline were present in 2853 (44.7%) of individuals with COPD. High fibrinogen was associated with an increased risk of hospitalized COPD exacerbations within 12 months (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.39-1.93) among participants in the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. High fibrinogen was associated with an increased risk of death within 36 months (HR: 1.94; 95% CI: 1.62-2.31) among all participants.
  
  
  CONCLUSIONS
  Fibrinogen levels ≥ 350 mg/dL identify COPD individuals at an increased risk of exacerbations and death and could be a useful biomarker for enriching clinical trials in the COPD population.
authors: Department of Preventive Medicine and Environmental Health, University of Kentucky, College of Public Health, Lexington.
authors: David M
authors: DM
authors: Mannino
authors: Respiratory Therapy Area Unit, GlaxoSmithKline, Philadelphia, Pennsylvania.
authors: Ruth
authors: R
authors: Tal-Singer
authors: Wolfson Institute for Biomedical Research, University College London, United Kingdom.
authors: David A
authors: DA
authors: Lomas
authors: Department of Respiratory Medicine, Odense University Hospital & University of Southern Denmark, Odense, Denmark, and Manchester Academic Health Science Centre, University of Manchester, United Kingdom.
authors: Jorgen
authors: J
authors: Vestbo
authors: Department of Medicine, Department of Epidemiology, Columbia University Medical Center, New York, New York.
authors: R
authors: R
authors: Graham Barr
authors: Therapeutic Area Respiratory Diseases, Boehringer Ingelheim Pharma GmbH Co KG, Ingelheim, Germany, and Department of Sports Medicine, Medical Clinic V, University of Tuebingen, Germany.
authors: Kay
authors: K
authors: Tetzlaff
authors: Global Regulatory Affairs, GlaxoSmithKline Research and Development, Middlesex, United Kingdom.
authors: Michael
authors: M
authors: Lowings
authors: Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha.
authors: Stephen I
authors: SI
authors: Rennard
authors: Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut.
authors: Jeffrey
authors: J
authors: Snyder
authors: Global Medicine Development, AstraZeneca LP, Wilmington, Delaware.
authors: Mitchell
authors: M
authors: Goldman
authors: Global Medicine Development, AstraZeneca LP, Wilmington, Delaware.
authors: Ubaldo J
authors: UJ
authors: Martin
authors: COPD Foundation, Washington, D.C.
authors: Deborah
authors: D
authors: Merrill
authors: Health Economics and Epidemiology, Evidera, Lexington, Massachusetts.
authors: Amber L
authors: AL
authors: Martin
authors: Health Economics and Epidemiology, Evidera, Lexington, Massachusetts.
authors: Jason C
authors: JC
authors: Simeone
authors: Health Economics and Epidemiology, Evidera, Lexington, Massachusetts.
authors: Kyle
authors: K
authors: Fahrbach
authors: Health Economics and Epidemiology, Evidera, Lexington, Massachusetts.
authors: Brian
authors: B
authors: Murphy
authors: Health Economics and Epidemiology, Evidera, Lexington, Massachusetts.
authors: Nancy
authors: N
authors: Leidy
authors: Respiratory Therapy Area Unit, GlaxoSmithKline, Philadelphia, Pennsylvania.
authors: Bruce
authors: B
authors: Miller
keywords: COPD; biomarker; fibrinogen