Phenotyping COPD exacerbations using imaging and blood-based biomarkers

Abstract

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.

Materials and methods: Subjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman's correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters.

Results: A total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV₁ 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, P<0.001), pulmonary edema (AUC =0.63, P=0.009), and pleural effusion on CXR (AUC =0.64, P=0.01); whereas on CT images, NT-proBNP concentrations were associated with pleural effusion (AUC =0.71, P=0.002). Serum CRP concentrations, on the other hand, were associated with consolidation on CT images (AUC =0.75, P<0.001), ground glass opacities (AUC =0.64, P=0.028), and pleural effusion (AUC =0.72, P<0.001) on CT images. A serum CRP sensitivity-oriented cutoff point of 11.5 mg/L was selected for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which has a sensitivity of 91% and a specificity of 53% (P<0.001).

Conclusion: Elevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.

Keywords: CT scan; biomarker; chest X-ray; chronic obstructive pulmonary disease; exacerbation.

Figure 1

Study flow diagram. Note: All subjects had radiological imaging and blood-based biomarker measurements within 10 days of each other. Abbreviations: CXR, chest X-ray; CT scan, computed tomography; NT-proBNP, N-terminal of the prohormone brain natriuretic peptide; CRP, C-reactive protein.

Figure 2

ROC curves for the chest CT scan parameters of clinical interest and blood-based biomarkers. Notes: ROC curves for the CT parameters of clinical interest with and without adjustment for age and sex. (A) CRP and consolidation. (B) CRP and pleural effusion. (C) NT-proBNP and pleural effusion. Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CT, computed tomography; NT-proBNP, N-terminal of the prohormone brain natriuretic peptide; CRP, C-reactive protein.