Abstract
BACKGROUND: The heterogeneous nature of chronic obstructive pulmonary disease (COPD) complicates the identification of the predictors of disease progression. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features. METHODS: We included 4496 smokers with available data from their enrollment and 5-year follow-up visits in the COPD Genetic Epidemiology (COPDGene(®)) study. We constructed linear regression (LR) and supervised random forest models to predict 5-year progression in forced expiratory in 1 second (FEV(1)) from 46 baseline features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit. RESULTS: Predicting the change in FEV(1) over time is more challenging than simply predicting the future absolute FEV(1) level. For random forest, R-squared was 0.15 and the area under the receiver operator characteristic (ROC) curves for the prediction of participants in the top quartile of observed progression was 0.71 (testing) and respectively, 0.10 and 0.70 (validation). Random forest provided slightly better performance than LR. The accuracy was best for Global initiative for chronic Obstructive Lung Disease (GOLD) grades 1-2 participants, and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD. CONCLUSION: Random forest, along with deep phenotyping, predicts FEV(1) progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.