Abstract
Objective
This study aims to systematically investigate the relationship between serum perfluoroalkyl and polyfluoroalkyl substances (PFAS) and chronic obstructive pulmonary disease (COPD), along with its potential mechanisms, through a combination of population analysis and bioinformatics approaches.Method
To explore the association between serum PFAS levels and COPD, we utilized data from the National Health and Nutrition Examination Survey (NHANES) covering three cycles from 2013 to 2018. We specifically analyzed the relationship between COPD patient data and levels of five PFAS compounds: perfluorodecanoic acid (PFDeA), 2-(N-methyl perfluorooctanesulfonamide) acetic acid (Me-PFOSA-AcOH), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluoroundecanoic acid (PFUA). Additionally, we employed a combination of network toxicology, transcriptomic analysis, and molecular docking to elucidate the potential mechanisms underlying this association.Results
This study encompassed 4939 participants and identified statistically significant differences in the levels of PFDeA and Me-PFOSA-AcOH between the COPD group and the control group (P Conclusion
This study identified cross-sectional associations between several serum PFAS concentrations and self-reported physician-diagnosed COPD, with PFDeA showing a non-linear exposure-response pattern. Transcriptomic analyses and molecular docking further provided hypothesis-generating clues implicating inflammation- and extracellular matrix-related genes and pathways. Given the cross-sectional design, the potential for reverse causation, and residual confounding, these findings should not be interpreted as evidence of causality. Further longitudinal and experimental studies are warranted to validate these observations and clarify their biological relevance.