Disentangling Predictors of COPD Mortality with Probabilistic Graphical Models

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in COPD patients can be important for disease management strategies. Although scores for all-cause mortality have been developed previously, there is limited research on factors that may directly affect COPD-specific mortality. We used probabilistic (causal) graphs to analyze clinical baseline COPDGene data, including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data (from year-5). We identified factors linked to all-cause and COPD-specific mortality. Although many were similar, there were differences in certain comorbidities (all-cause mortality model only) and forced vital capacity (COPD-specific mortality model only). Using our results, we developed VAPORED, a 7-variable COPD-specific mortality risk score, which we validated using the ECLIPSE 3-yr mortality data. We showed that the new model is more accurate than the existing ADO, BODE, and updated BODE indices. Additionally, we identified biological signatures linked to all-cause mortality, including a plasma cell mediated component. Finally, we developed a web page to help clinicians calculate mortality risk using VAPORED, ADO, and BODE indices. Given the importance of predicting COPD-specific and all-cause mortality risk in COPD patients, we showed that probabilistic graphs can identify the features most directly affecting them, and be used to build new, more accurate models of mortality risk. Novel biological features affecting mortality were also identified. This is an important step towards improving our identification of high-risk patients and potential biological mechanisms that drive COPD mortality.