Phthalate Exposure and Oxidative/Nitrosative Stress in Childhood Asthma: A Nested Case-Control Study with Propensity Score Matching

Abstract

Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers—8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA)—using a propensity score-matched case-control study (case vs. control = 41 vs. 111). The median monobenzyl phthalate (MBzP) concentrations in the case group were significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p = 0.02), indicating that dust could be an important source. After adjustment for confounders, the associations of high monomethyl phthalate (MMP) (75th percentile) with 8-NO2Gua (adjusted odds ratio (aOR): 2.66, 95% confidence interval (CI): 1.03–6.92) and 8-isoPF2α (aOR: 4.04, 95% CI: 1.51–10.8) and the associations of mono-iso-butyl phthalate (MiBP) with 8-isoPF2α (aOR: 2.96, 95% CI: 1.13–7.79) were observed. Weighted quantile sum regression revealed that MBzP contributed more than half of the association (56.8%), followed by MiBP (26.6%) and mono-iso-nonyl phthalate (MiNP) (8.77%). Our findings supported the adjuvant effect of phthalates in enhancing the immune system response.