UBC Theses and Dissertations
Biomarkers for acute exacerbation of chronic obstructive pulmonary disease Chen, Roy Yu-Wei
Rationale: There are currently no generally accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). There is an urgent need of biomarkers that can guide therapeutic management in AECOPD. Based on literature review, systemic inflammation and mild cardiac dysfunction are often associated with AECOPD. We hypothesized that certain protein markers can indeed be useful in tracking and diagnosing AECOPD progression. Methods: The study cohort consisted of 368 patients recruited in the chronic obstructive pulmonary disease (COPD) Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 76 stable COPD patients who served as controls. We first determined the relationship of AECOPD of C-reactive protein (CRP) and the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP). We then performed a discriminatory analysis using receiver-operating characteristics (ROC) curve in a logistic regression model. We compared the area under the curve (AUC) of 4 different combinations of CRP and NT-proBNP models. Lastly, we examined several potential biomarkers that were implicated in AECOPD. Results: The demographic data of the cohort and the controls were well matched, with an average age of 68 versus 65 years old, 64% versus 77% male, and a forced expiratory volume in 1 second (FEV1) % predicted of 52% versus 58%. The CRP and NT-proBNP levels at exacerbation onset were found to be the highest and progressively decreased over time. Of the 4 models of ROC curves, the leave-one-out cross-validated model including both CRP and NT-proBNP had an AUC of 0.80. This model replicated well in an external LEUKO dataset. On the ii other hand, D-Dimer, pulmonary and activation-regulated chemokine (PARC) and troponin I, showed minimal or no temporal changes during hospitalization and were no different than those with stable COPD. Conclusions: In summary, this thesis demonstrated that biomarkers such as CRP and NT-proBNP are significantly elevated during AECOPD and decreased with recovery. Secondly, a combination of CRP and NT-proBNP could discriminate patients who were hospitalized for their AECOPD from stable patients. Together, these two biomarkers show promise in diagnosing and tracking AECOPD.
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