Perfluorinated chemicals and adolescent respiratory health: Epidemiological evidence and mechanistic insights

TL;DR

This study explores how exposure to perfluorinated chemicals affects lung health in adolescents, using both population data and molecular modeling.

Contribution

The study integrates epidemiological and computational methods to reveal how PFCs may harm adolescent respiratory health through oxidative stress and specific protein targets.

Findings

PFOA, PFHS, and PFOS were significantly linked to reduced pulmonary function in adolescents.

PFOA was identified as the main contributor to respiratory effects, partly mediated through oxidative stress.

Key proteins like INS, AKT1, and TNF were found to be potential targets linking PFC exposure to respiratory outcomes.

Abstract

Perfluorinated compounds (PFCs) are persistent environmental pollutants with near-universal human exposure, yet their respiratory health impacts during adolescence remain insufficiently explored. This investigation evaluated single and combined effects of serum PFCs on pulmonary function and respiratory morbidity in a nationally representative adolescent cohort (n = 976, ages 12–19 years) utilizing 2007–2012 NHANES data. Advanced analytical approaches including multivariable regression, mixture modeling (BKMR and WQS), and mediation analysis were employed to assess associations with spirometric parameters (FEV1, FVC, FEV1/FVC) and respiratory symptoms while examining inflammatory and oxidative stress pathways. Computational approaches integrating network toxicology and molecular docking identified key protein targets. Analytical results demonstrated significant associations between specific PFC congeners (PFOA, PFHS, PFOS) and pulmonary function measures, with age-stratified effects observed for wheezing symptoms. Mixture analyses revealed PFOA as the predominant contributor to observed respiratory effects, partially mediated through oxidative stress pathways (6.8–8.2% mediation). Molecular investigations identified critical signaling nodes (INS, AKT1, TP53, TNF, IL6, ALB and PPARγ) potentially linking PFC exposure to respiratory outcomes. These findings provide mechanistic insights into PFC-induced pulmonary effects during adolescence, highlighting the need for continued investigation of these environmentally persistent compounds’ impact on developing respiratory systems. The integrated epidemiological-computational approach demonstrates the utility of combining population-level data with mechanistic modeling to elucidate environmental health effects.

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