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

Date Published: March 22, 2017

Publisher: Public Library of Science

Author(s): Yu-wei Roy Chen, Virginia Chen, Zsuzsanna Hollander, Jonathon A. Leipsic, Cameron J. Hague, Mari L. DeMarco, J. Mark FitzGerald, Bruce M. McManus, Raymond T. Ng, Don D. Sin, Stelios Loukides.


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.

Partial Text

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 [2–4]. There is a pressing need to objectify these events to enable more accurate endotyping of these events and to ensure prompt implementation of appropriate therapy.

Demographic data and lung function measurements of the discovery set are shown in Table 1. 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. Additional data on the validation set are in Table A of the S1 File.

In this study, we noted the following key findings: firstly, circulating blood CRP and NT-proBNP were both elevated during AECOPDs requiring hospitalization and decreased with treatment during the recovery phase of the hospitalization; secondly, the two biomarkers were, however, weakly correlated and NT-proBNP but not CRP concentrations were significantly associated with total mortality and length of hospitalizations, suggesting that they may reflect distinct pathways and may correspond to different endotypes of AECOPD; thirdly, using the LOOCV method, a combination of CRP and NT-proBNP discriminated with reasonable AUCs patients experiencing acute hospitalization for their AECOPD from those who were stable; and lastly, our models were replicated in a validation set of COPD patients with reproducible AUCs that were comparable to the discovery set, providing support for the use of these two biomarkers in combination to diagnose AECOPD.




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