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Phenotyping chronic obstructive pulmonary disease exacerbations

University of British Columbia

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]), blood tests(C-reactive protein [CRP] and the N-terminal of the prohormone brain natriuretic peptide [NT-proBNP]), and a molecular pathogen detection method. Methods: Subjects who were hospitalized with a primary diagnosis of AECOPD were enrolled in the Rapid Transition Program(RTP). We examined a subset of subjects who had had CXRs, CT scans, and blood collected for CRP and NT-proBNP. A radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted the CXRs and CT images. Logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters. Sputum samples in a subset of subjects were tested by a molecular pathogen detection method to phenotype AECOPD into non-infectious, bacterial, and virally-associated phenotypes. Differences between the phenotypes in terms of clinical features, CRP and NT-proBNP concentrations, complete blood counts, and 1-year mortality rate were examined. Results: NT-proBNP was associated with cardiac enlargement, pulmonary edema, and pleural effusion on CXR, whereas on CT images, NT-proBNP was associated with pleural effusion. CRP, on the other hand, was associated with consolidation, ground glass opacities, and pleural effusion on CT images. A CRP sensitivity-oriented cut-point of 11.5 mg/L was reached by setting a minimum sensitivity of 90% and applying the Youden index, for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which had a sensitivity of 91% and a specificity of 53% (P<0.001). Subjects who had a negative result on the molecular pathogen detection array had higher NT-proBNP, lower hemoglobin, and higher RDW compared to the subjects who had a positive result. Conclusions: In summary, this thesis demonstrated that elevated CRP may indicate pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction, and having a negative result on the respiratory pathogen array may indicate a non-infectious causation of AECOPD. These readily available tests may provide more accurate phenotyping of AECOPD, and may lead to better treatment strategies and resource utilization in subjects admitted with AECOPD.

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2018-01-17

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/64386

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/