Development of an automated machine learning classifier for chronic obstructive pulmonary disease in non-small cell lung cancer patients using electronic health records

Chronic obstructive pulmonary disease (COPD) affects 40–60% of non-small cell lung cancer (NSCLC) patients but remains frequently underdiagnosed and undertreated, contributing to adverse outcomes [1]. Our objective was to develop an automated machine learning (ML) classifier to identify potential COPD, and potentially untreated COPD among NSCLC patients. We performed a retrospective cohort study of 4,604 NSCLC patients. Manual chart review (development set; DS; [ n = 600]; test set; TS; [ n = 294]), using Global Initiative for Obstructive Lung Disease (GOLD) criteria, served as the reference standard for COPD diagnosis. Predictor selection used least-absolute-shrinkage-and-selection-operator (LASSO) logistic regression. Two logit thresholds were chosen to create binary classifiers: a ≥ 95% specificity quality-improvement threshold (QIT) for COPD identification, and Youden’s index threshold (YT) for survival analysis and association with radiographic emphysema. The classifier achieved an area-under-the-receiver-operating-characteristic-curve of 0.93 in the DS and TS (95% CI:0.91–0.95; 95% CI:0.91–0.96, respectively). The QIT yielded logit cutoffs ≥ 0.9242 (DS) and ≥ 0.9625 (TS), with sensitivities 69% and 72%, specificities 95% and 96%, positive-predictive-value (PPV) 93%, and negative-predictive-value (NPV) 77% and 80%, respectively. In the DS and TS, potential COPD prevalence was 48% and 46%, with 41% and 46% potentially untreated; the QIT-classifier identified 69% and 72% of potential COPD cases and 40% and 50% of potentially untreated cases, respectively (PPV 85%, 95% CI:73–93% and 86%, 95% CI:71–95%). YT yielded a sensitivity and specificity of 88%. In Cox-proportional hazards models ( n = 4,501, 1,959 deaths), the YT-COPD classifier was associated with increased mortality, with significant effect measure modification by clinical stage ( p = 0.003; stratified HR YT-COPD: stage I: 1.71, 95% CI:1.30–2.44, p < 0.001; Stage II: 1.72, 95% CI:1.15–2.59, p = 0.009; Stage III: 1.67, 95% CI:1.34–2.08, p < 0.001; Stage IV: 1.29, 95% CI:1.15–1.44, p < 0.001). Furthermore, classifier-predicted COPD (YT) was strongly associated with radiographic emphysema ( p < 0.001). This ML classifier effectively emulates structured chart review to identify potential COPD and potentially untreated COPD in NSCLC, with prognostic validity and potential for scalable, low-cost quality improvement and research. External validation in other institutions and EHR systems is warranted before broader implementation.