Co-exposure effects of urinary polycyclic aromatic hydrocarbons and metals on lung function: Mediating role of systematic inflammation

Abstract Background: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown. Methods: Among 1,123 adults from National Health and Nutrition Examination Survey 2011-2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp) were used to estimate co-exposure effects on lung function. Meditation analyses were used to explore mediating role of WBC. Results: These models demonstrated that PAHs and metals were significantly associated with lung function. BKMR models showed that comparing to all chemicals fixed at median level, FEV₁/FVC, PEF, and FEF25-75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the qgcomp, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV₁, FEV₁/FVC, PEF, and FEF25-75%, respectively. The 2-OHPh, 3-OHFlu, and Cd were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function. Conclusions: Co-exposure of PAHs and metals leads to lung function impairment, and WBC could partially mediate the relationship. Our findings clarify co-exposure effects of environmental mixtures on respiratory health and underlying mechanism, and suggest that focusing on highly prioritized toxicants would effectively attenuate the adverse effects.