Impact of serum PFAS levels on chronic obstructive pulmonary disease: A comprehensive analysis.
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.
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.
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 < 0.05). After controlling for potential confounding variables, logistic regression analysis demonstrated that both PFDeA and PFUA are statistically associated after covariate adjustment to COPD (PFDeA: OR = 0.23, 95% CI: 0.06-0.87; PFUA: OR = 0.06, 95% CI: 0.01-0.47). Weighted Quantile Sum (WQS) regression analysis indicated a positive relationship between cumulative serum PFAS levels and the prevalence of self-reported physician-diagnosed COPD (P = 0.011). Furthermore, restricted cubic spline (RCS) analysis revealed a nonlinear relationship between PFDeA and COPD, which was statistically significant (P-overall = 0.008, P-nonlinear = 0.003). Network toxicology and transcriptomic analysis suggested that PFDeA may influence COPD by modulating several biological pathways, including the collagen catabolic process, thyroid hormone metabolism, extracellular matrix (ECM) disaggregation, endolysosomal function, collagen binding, Toll-like receptor signaling, lysosomal activity, and apoptosis, through the regulation of genes such as PTGS1, CTSK, TLR9, MMP9, and CTSB. Molecular docking studies indicated that the binding free energy of PFDeA with these molecular targets ranged from -8.2 to -6.3 kcal/mol.
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.
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.
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 < 0.05). After controlling for potential confounding variables, logistic regression analysis demonstrated that both PFDeA and PFUA are statistically associated after covariate adjustment to COPD (PFDeA: OR = 0.23, 95% CI: 0.06-0.87; PFUA: OR = 0.06, 95% CI: 0.01-0.47). Weighted Quantile Sum (WQS) regression analysis indicated a positive relationship between cumulative serum PFAS levels and the prevalence of self-reported physician-diagnosed COPD (P = 0.011). Furthermore, restricted cubic spline (RCS) analysis revealed a nonlinear relationship between PFDeA and COPD, which was statistically significant (P-overall = 0.008, P-nonlinear = 0.003). Network toxicology and transcriptomic analysis suggested that PFDeA may influence COPD by modulating several biological pathways, including the collagen catabolic process, thyroid hormone metabolism, extracellular matrix (ECM) disaggregation, endolysosomal function, collagen binding, Toll-like receptor signaling, lysosomal activity, and apoptosis, through the regulation of genes such as PTGS1, CTSK, TLR9, MMP9, and CTSB. Molecular docking studies indicated that the binding free energy of PFDeA with these molecular targets ranged from -8.2 to -6.3 kcal/mol.
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.