title: Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Accurate prediction of mortality helps select patients for interventions aimed at improving outcome.
  
  
  OBJECTIVE
  Because chronic obstructive pulmonary disease is characterized by low-grade systemic inflammation, we hypothesized that addition of inflammatory biomarkers to established predictive factors will improve accuracy.
  
  
  METHODS
  A total of 1,843 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study were followed for 3 years. Kaplan-Meier curves, log-rank analysis, and Cox proportional hazards analyses determined the predictive value for mortality of clinical variables, while C statistics assessed the added discriminative power offered by addition of biomarkers.
  
  
  RESULTS
  At recruitment we measured anthropometrics, spirometry, 6-minute walk distance, dyspnea, BODE index, history of hospitalization, comorbidities, and computed tomography scan emphysema. White blood cell and neutrophil counts, serum or plasma levels of fibrinogen, chemokine ligand 18, surfactant protein D, C-reactive protein, Clara cell secretory protein-16, IL-6 and -8, and tumor necrosis factor-α were determined at recruitment and subsequent visits. A total of 168 of the 1,843 patients (9.1%) died. Nonsurvivors were older and had more severe airflow limitation, increased dyspnea, higher BODE score, more emphysema, and higher rates of comorbidities and history of hospitalizations. The best predictive model for mortality using clinical variables included age, BODE, and hospitalization history (C statistic of 0.686; P < 0.001). One single biomarker (IL-6) significantly improved the C statistic to 0.708, but this was further improved to 0.726 (P = 0.003) by the addition of all biomarkers.
  
  
  CONCLUSIONS
  The addition of a panel of selected biomarkers improves the ability of established clinical variables to predict mortality in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).
authors.affiliation: Pulmonary and Critical Care Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. bcelli@partners.org
authors.forename: Bartolome R
authors.initials: BR
authors.lastname: Celli
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.forename: Julie
authors.initials: J
authors.lastname: Yates
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Peter
authors.initials: P
authors.lastname: Calverley
authors.forename: Harvey
authors.initials: H
authors.lastname: Coxson
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Annelyse
authors.initials: A
authors.lastname: Duvoix
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: Edwin
authors.initials: E
authors.lastname: Silverman
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Emiel
authors.initials: E
authors.lastname: Wouters
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003661:Decision Support Techniques; D005260:Female; D006760:Hospitalization; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000150:complications / Q000401:mortality*
chemical_list: D015415:Biomarkers