Associations between Phthalate Exposure, Immune Response, and lung Function in Taiwanese Adults

Abstract Background Experimental studies have indicated that phthalate exposure may influence immune function, while other studies suggest that immune responses may impact lung function. However, the epidemiological evidence connecting phthalate exposure, immune response markers, and lung function is limited. This study aims to investigate these associations and explore potential mediation and interaction effects. Methods Data from healthy adults in the Taiwan Biobank (baseline 2008–2015; follow-up 2011–2020) were analyzed (N = 759). At baseline, 10 urinary phthalate metabolites were measured including monoethyl phthalate (MEP) mono（2-ethyl-5-oxy-hexyl）phthalate (MEOHP), mono（2-ethyl-5-hydroxyhexyl）phthalate (MEHHP), and mono（2-ethyl-5-carboxypentyl）phthalate (MECPP). Immune indicators were estimated using DNA methylation data for granulocytes, CD4+ T cells, and CD8+ T cells. Lung function at follow-up was assessed via predicted FVC, FEV₁, and FEV₁/FVC. Generalized linear models and mediation models assessed associations, interactions and mediating effects, respectively. Results MEP was positively associated with granulocytes (β = 0.009, 95% CI: 0.002, 0.015), while MEHHP was positively associated with CD4+ T cells (β = 0.030, 95% CI: 0.001, 0.059). MEHHP and MECPP were inversely associated with FEV₁/FVC (β= -0.014, 95% CI: -0.025, -0.003 for MEHHP; β= -0.016, 95% CI: -0.032, -0.001 for MECPP). 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). Significant interactions between MEHHP and MEOHP levels and CD8+ T cell levels with FEV₁ and FEV₁/FVC were observed. Conclusions Exposure to specific phthalates or increased levels of certain immune cells may be linked to the risk of impaired lung function. Additionally, the association between phthalate exposure and lung function impairment may be affected by elevated immune responses. Key messages • Phthalate exposure and immune dysregulation may increase the risk of impaired lung function in adults. • Associations between phthalate exposure and lung function may be dependent on immune responses.