Immune response as a modifier linking phthalate exposure to lung function decline: Results from a longitudinal study

Experimental studies have suggested that phthalate exposure influences immune function and that immune responses may affect lung function. However, epidemiological evidence connecting phthalate exposure, immune response markers, and lung function remains limited. In this study, these associations and potential mediation and interaction effects were investigated. Data were collected from 759 community-dwelling individuals in the Taiwan Biobank cohort. The concentrations of 11 urinary phthalate metabolites were quantified. Immune biomarkers were estimated through DNA methylation analysis for granulocytes, monocytes, B cell, CD4⁺ T cells, CD8⁺ T cells, and natural killer cells. Lung function was evaluated according to percent predicted forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), and the FEV₁/FVC ratio. Generalized linear models were applied to examine the associations and interactions between the study variables. Quantile g-computation was performed to evaluate overall mixture effects. MEP was positively associated with granulocytes (β = 0.009, 95% confidence interval [CI]: 0.002, 0.015). MEHHP was positively associated with CD4⁺ T cells (β = 0.030, 95% CI: 0.001, 0.059). MEHHP (β = -0.014, 95% CI: -0.025, -0.003) and MECPP (β = -0.016, 95% CI: -0.032, -0.001) were inversely associated with FEV₁/FVC. MEOHP was negatively associated with both predicted FEV₁ (β = -0.027, 95% CI: -0.050, -0.005) and FEV₁/FVC (β = -0.018, 95% CI: -0.033, -0.002). MBzP and MCMHP and CD8⁺ T cell levels exerted a significant interaction effect on FEV₁/FVC. Exposure to specific phthalates or increased levels of certain immune cells may correlate with lung function impairment. Elevated immune responses may exacerbate the association between phthalate exposure and lung function impairment in our exploratory data. Further longitudinal research is required to determine the exact directionality and biological mechanism involved.