Mixture effects of air pollutants on children’s urinary levels of 8-isoprostane, a biomarker of oxidative stress

Abstract

BACKGROUND AND AIM: In single-pollutant models, individual air pollutants are reported to be associated with elevated levels of urinary 8-isoprostane, a marker of oxidative stress. Several air pollutants are highly correlated and might have joint effects in inducing oxidative stress, best assessed using mixture methods. METHODS: Urinary total 8-isoprostane was measured in 299 children (ages 6–8) from the Fresno, CA area and adjusted for creatinine levels. Individual-level exposure to seven pollutants: (sum of 4-, 5-, and 6-ring polycyclic aromatic hydrocarbon compounds (PAH456), nitrogen dioxide (NO₂), carbon monoxide (CO), ozone (O₃), elemental carbon (EC), and particulate matter 2.5 μm (PM2.5) and 10 μm in diameter (PM10)) at the primary residential location was modelled with a spatiotemporal model up to a year prior to outcome assessment. To estimate mixture cumulative, potential non-linear and interactions in effects of pollutants on levels of 8-isoprostane, we relied on weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). RESULTS:WQS regression indicated a 70% (95% CI: 11%, 130%) increase in the urinary levels of the 8-isoprostane associated with a tertile increase in the WQS index of the air pollution mixture averaged over a 6-month period. O₃, EC and PAH456 contributed most to this overall mixture effect (sum of average weights = 79%). Associations were lower in magnitude and CIs included the null for other exposure windows. BKMR did not yield a significant mixture effect, although, similar to WQS, this model highlighted O₃, EC, and PAH456 as important contributors to the overall mixture effect (posterior inclusion probabilities range: 41 to 57%). BKMR was also suggestive of interactions between various pollutants. CONCLUSIONS:Air pollutants may induce cumulative and joint oxidative stress effects in children. Future studies with larger samples may help confirm findings on the magnitude of mixture effects as well as presence of interactions between pollutants. KEYWORDS: Air pollution, Mixtures, Oxidative stress