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

Yu-Wei Roy Chen,Mari L Demarco,Raymond T Ng,J Mark Fitzgerald,Jonathon A Leipsic,Virginia Chen,Zsuzsanna Hollander,Bruce M Mcmanus,Cameron J Hague,Don D Sin,Stelios Loukides

doi:10.1371/journal.pone.0174063

Abstract

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.

Highlights

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and debilitating disease that affects 200 million people worldwide and is responsible for 3 million deaths annually [1]. Most of these deaths occur during periods of worsening of symptoms, which are called acute exacerbations of COPD (AECOPD) [1]
As inflammatory events associated with exacerbation can impact both the pulmonary and cardiac systems, our aim was to first investigate the temporal relationship between C-reactive protein (CRP) and NT-proBNP during AECOPD
There were no significant differences in the baseline characteristics between patients with AECOPD and stable patients except for smoking status, and the use of inhaled corticosteroids, and prednisone

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and debilitating disease that affects 200 million people worldwide and is responsible for 3 million deaths annually [1] Most of these deaths occur during periods of worsening of symptoms, which are called acute exacerbations of COPD (AECOPD) [1]. Because exacerbations are defined purely based on a health professionals’ interpretation of patient symptoms, the accuracy of the current definition of AECOPD is uncertain. This may in part explain the heterogeneity of clinical presentation and outcomes of these events and the variable response to therapy [2,3,4]. CRP is associated with all-cause, cardiovascular, and cancer mortality [14]

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