Developing an interpretable machine learning predictive model of chronic obstructive pulmonary disease by serum PFAS concentration

TL;DR

This study uses machine learning to predict COPD risk based on blood levels of PFAS chemicals, finding some are protective while others increase risk.

Contribution

Applies interpretable machine learning to PFAS-COPD association and provides a public web-based risk calculator.

Findings

CatBoost model achieved 84% accuracy and 0.89 AUC in predicting COPD from PFAS levels.

PFOS and PFUA were associated with reduced COPD risk, while PFOA and MPAH increased risk.

SHAP analysis clarified variable contributions and individual prediction explanations.

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, with limited early detection strategies. While previous studies have examined the relationship between per- and polyfluoroalkyl substances (PFAS) and COPD, limited research has applied interpretable machine learning (ML) techniques to this association.

We investigated the association between PFAS exposure and COPD risk in 4,450 National Health and Nutrition Examination Survey (NHANES) participants from 2013 to 2018. After excluding missing covariates and extreme PFAS values and applying K-nearest neighbors (KNN) imputation, nine ML models, including CatBoost, were built and evaluated using metrics like accuracy, area under the curve (AUC), sensitivity, and specificity. The best-performing model was further analyzed using partial dependence plots (PDP) and SHapley additive exPlanations (SHAP) analysis. To enhance clinical applicability, the final model was deployed as a publicly accessible web-based risk calculator.

CatBoost emerged as the best model, achieving an accuracy of 84%, AUC of 0.89, sensitivity of 81%, and specificity of 84%. PDP revealed that higher perfluorooctane sulfonic acid (PFOS) and perfluoroundecanoic acid (PFUA) levels were associated with reduced COPD risk, whereas perfluorooctanoic acid (PFOA) and 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (MPAH) showed positive associations with COPD. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDE), and perfluorohexane sulfonic acid (PFHxS) demonstrated mixed or non-linear effects. SHAP analysis provided insights into individual predictions and overall variable contributions, clarifying the complex PFAS-COPD relationship. The deployed web-based calculator enables interactive prediction and risk interpretation, supporting potential public health applications.

CatBoost identified PFOS and PFUA as protective factors against COPD, while PFOA and MPAH increased risk of COPD. These findings emphasize the need for stricter PFAS regulation and highlight the potential of machine learning in guiding prevention strategies.

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