Phthalate Exposures and Oxidative/ Nitrosative Stress among Childhood Asthma: A nested Case-Control Study with Propensity Score Matching

BACKGROUND AND AIM: Whether low-dose phthalates exposure trigger children’s asthma and underlying mechanisms are still under debate. Recent studies revealed that oxidative/ nitrosative stress and lipid peroxidation may play as a mediator of phthalate exposure on certain respiratory outcomes. We aims to evaluate the individual and mixed effects of low-dose phthalate exposure on asthmatic children, and to assess the mediating effect of five (oxidative/nitrosative stress/ lipid peroxidation stress) mechanistic biomarkers, 8-OHdG, 8-NO₂Gua, HNE-MA, 8-isoPF2α and MDA, on the association between phthalate exposure and asthmas. METHODS: We conducted a case-control study using propensity score matching, including 41 asthma and 111 controls. Eleven phthalate metabolites and oxidative/nitrosative stress biomarkers have been analyzed by LC-MS/MS and ELISA, respectively. The association among high oxidative/nitrosative stress biomarker, high urinary phthalate metabolites level (75th %tile) and risk of asthma was analyzed by conditional logistic regression. Weighted Quantile Sum Regression will also be used to estimate the contribution of individual exposure. RESULTS: The median MBzP concentrations in the case groups was significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p= 0.02), which indicated dust could be an important source. After adjustment for confounding factors, some associations between certain oxidative stress biomarkers and phthalate metabolites were found, such as MMP with 8-NO₂Gua (OR: 2.66, 95% CI: 1.03–6.92) and 8-isoPF2α (OR: 4.04, 1.51–10.8), and MiBP with 8-isoPF2α (OR: 2.96, 1.13–7.79). We found MBzP contributed more than a half of the association (56.8%), followed by MiBP (26.6%) and MiNP (8.77%). However, there is no significant association between higher phthalate metabolites levels or oxidative stress biomarkers with risk of asthma. CONCLUSIONS: Our findings supported the adjuvant effect of phthalates in enhancing immune system response. However, no clear evidence of a link between higher oxidative stress biomarkers and asthma, possibly due to limited sample size and exposure window.