Phenotyping COPD exacerbations using imaging and blood-based biomarkers

Abstract

RationaleAcute 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 methodsSubjects 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.ResultsA 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).ConclusionElevated 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.

<p>Thoracic Imaging at Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review</p>

“…In general, most studies discussed imaging biomarkers either as prevalence values of radiological findings in a population of subjects with an exacerbation of COPD, or as quantitative measurements of an imaging feature. A total of 10 of the 51 papers [9][10][11][12][13][14][15][16][17][18] presented quantitative measurements of imaging features at exacerbation. One paper presented quantitative individual patient data, but no cohort averages, 19 and the remaining 40 papers presented prevalence values for established radiological or other features.…”

“…Van Geffen et al additionally reported a decrease in total airway volume. Alotaibi et al 9 also reported a high (67.5%) prevalence of airway thickening on CT, although this latter study only examined a single time-point scan. Figure 2 Summary: The Pathophysiology of a COPD Exacerbation in relation to Imaging Biomarkers.…”

Consolidation and Exacerbation of COPD

“…Increasingly, patients admitted to hospital with COPD undergo computed tomography (CT) scanning. It is not clear, at present, whether the presence of consolidation on CT has the same prognostic significance as consolidation on chest X-ray (CXR), but a recent study has reported that a serum CRP cutoff of 11.5 mg had a sensitivity of 91% and a specificity of 53% for CT consolidation [ 17 ].…”

Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease

“…65 Recently, the combination of CRP and CURB-65 has proven useful for predicting ICU admission and mortality in patients with CAP. 66 Although elevated CRP may predict the development of CT abnormalities, such as consolidation, ground glass opacities, and pleural effusion in patients with AECOPD, 67 admission levels can be used to predict CAP in patients with COPD. 15 In fact, using a lower quartile (CRP 3.5 mg/dL; OR ¼ 1) as a reference, there is a progressive increase in the risk of CAP for patients with CRP levels of 3.6 to 11.9 mg/dL (OR ¼ 4.02; 95% CI: 1.8-9.9), 12 to 20.4 mg/dL (OR ¼ 5.75; 95% CI: 3.2-12.7), and !20 mg/dL (OR ¼ 10.6; 95% CI: 4-25.4).…”