Leveraging Deep Learning of Chest Radiograph Images to Identify Individuals at High Risk for Chronic Obstructive Pulmonary Disease

BackgroundThis study assessed whether deep learning applied to routine outpatient chest X-rays (CXRs) can identify individuals at high risk for incident chronic obstructive pulmonary disease (COPD). MethodsUsing cancer screening trial data, we previously developed a convolutional neural network (CXR-Lung-Risk) to predict lung-related mortality from a CXR image. In this study, we externally validated CXR-Lung-Risk to predict incident COPD from routine CXRs. We identified outpatients without lung cancer, COPD, or emphysema who had a CXR taken from 2013-2014 at a Mass General Brigham site in Boston, Massachusetts. The primary outcome was 6-year incident COPD. Discrimination was assessed using AUC compared to the TargetCOPD clinical risk score. All analyses were stratified by smoking status. A secondary analysis was conducted in the Project Baseline Health Study (PBHS) to test associations between CXR-Lung-Risk with pulmonary function and protein abundance. FindingsThe primary analysis consisted of 12,550 ever-smokers (mean age 62{middle dot}4{+/-}6{middle dot}8 years, 48.9% male, 12.4% rate of 6-year COPD) and 15,298 never-smokers (mean age 63{middle dot}0{+/-}8{middle dot}1 years, 42.8% male, 3.8% rate of 6-year COPD). CXR-Lung-Risk had additive predictive value beyond the TargetCOPD score for 6-year incident COPD in both ever-smokers (CXR-Lung-Risk + TargetCOPD AUC: 0{middle dot}73 [95% CI: 0{middle dot}72-0{middle dot}74] vs. TargetCOPD alone AUC: 0{middle dot}66 [0{middle dot}65-0{middle dot}68], p<0{middle dot}01) and never-smokers (CXR-Lung-Risk + TargetCOPD AUC: 0{middle dot}70 [0{middle dot}67-0{middle dot}72] vs. TargetCOPD AUC: 0{middle dot}60 [0{middle dot}57-0{middle dot}62], p<0{middle dot}01). In secondary analyses of 2,097 individuals in the PBHS, CXR-Lung-Risk was associated with worse pulmonary function and with abundance of SCGB3A2 (secretoglobin family 3A member 2) and LYZ (lysozyme), proteins involved in pulmonary physiology. InterpretationIn external validation, a deep learning model applied to a routine CXR image identified individuals at high risk for incident COPD, beyond known risk factors. FundingThe Project Baseline Health Study and this analysis were funded by Verily Life Sciences, San Francisco, California. ClinicalTrials.gov IdentifierNCT03154346