Associations between phthalate metabolites and two novel systemic inflammatory indexes: A cross-sectional analysis of NHANES data

Abstract

Background The potential risky effects of phthalate metabolites on inflammation and immune function have attracted much attention in recent years. However, direct studies on the relationship between these metabolites and the systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are limited. Methods This cross-sectional study used Generalized linear regression models (GLM), Restricted cubic splines (RCS), Weighted quantile sum (WQS), and Bayesian kernel-machine regression (BKMR) to analyze data from 3,325 U.S. adults aged between 20 and 80 years, obtained from the U.S. National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. The study aimed to investigate the relationship between urine samples of nine phthalate metabolites and levels of SII and SIRI in a single, nonlinear, and mixed relationship, and explored the robustness of the findings under single and mixed effects using two sensitivity analyses for completeness. Furthermore, sex-specific differences in outcomes were explored by conducting stratified analyses to identify potentially significant subgroups. Results In single exposure analyses, MnBP, MEP, MBzP, and MEOHP were positively associated with SII and SIRI, and the associations were more pronounced in the female population. Except for MnBP, MBzP, and MiBP, the dose-exposure relationships between the other four phthalate metabolites and the two inflammatory indices were linear. The findings from the two mixed exposure models demonstrated a positive association between the collective concentrations of phthalate metabolites and levels of SII and SIRI. Additionally, an interplay was observed between the phthalate metabolites MBzP and MEHHP, with MBzP being identified as a significant contributor to the urinary levels of phthalate metabolites. The results of the two sensitivity analyses were in general agreement with the above findings. Conclusion Positive correlations were identified between phthalate metabolites and systemic inflammatory indexes SII and SIRI. Additionally, among the metabolites, MBzP was determined to have the most significant impact.