Exposure to urinary polycyclic aromatic hydrocarbon metabolites for the effect of lung function among children and adolescents: Epidemiological study and mechanism exploration

Human are widely exposed to polycyclic aromatic hydrocarbon (PAHs), but existing evidence about exposure to urinary PAHs metabolites for pulmonary health in children and adolescents is limited. Our aim was to examine the effect of single and mixed exposure of urinary PAHs metabolites on lung function among children and adolescents. We included 1417 individuals aged 6-19 years from 3 survey cycles (2007-2008, 2009-2010, 2011-2012) of NHANES program. Multivariable linear regression model was conducted to examine the relationship between urinary PAHs metabolites and lung function index including FEV₁, FVC and FEV₁/FVC. BKMR and WQS model were used to evaluate the joint effects of PAHs metabolites for lung function index. Mediation analyses were performed to investigate the mediating role of inflammation related index. Hub proteins were screened by network toxicology and validated using molecular docking. Our results indicated that 3-FLU was negatively linked with FEV₁ and FEV₁/FVC; 1-OHP was negatively linked with FEV₁; 1-PYR was negatively linked with FEV₁ and FVC. In addition, 3-OHP was positively corrected with three lung function parameters. In BKMR and WQS models, PAHs metabolites co-exposure was all negatively corrected with FEV₁ and FVC. Systemic inflammation response index mediated the relationship between I-PYR and FEV₁ as well as FVC, with the 8 % and 6 % proportion. IL-6, STAT3, TNF, and TP53 were screened and validated as the common targets related with PAHs, inflammation and lung function by molecular docking analysis. Taken together, our findings raise the concerns about the potential hazards of environmentally relevant PAHs metabolites exposure for respiratory system in the vulnerable population and guide future research into the toxic mechanisms of PAHs metabolites-mediated lung function injury, which has important public health implications.