C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations

PLoS One. 2017 Mar 22;12(3):e0174063. doi: 10.1371/journal.pone.0174063. eCollection 2017.


There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism*
  • Cohort Studies
  • Female
  • Hospitalization
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / metabolism*


  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Grants and funding

Funding was provided by Genome Canada, Genome British Columbia, Genome Quebec, the Canadian Institutes of Health Research, PROOF Centre of Excellence, St. Paul's Foundation, Providence Health Care Research Institute, the Canadian Respiratory Research Network, and the National Heart, Lung, and Blood Institute’s COPD Clinical Research Network (Grants U10 HL074441, U10 HL074418, U10 HL074428, U10 HL074409, U10 HL074407, U10 HL074422, U10 HL074416, U10 HL074408, U10 HL074439, U10 HL0744231, and U10 HL074424). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.