Individual and joint association of phenols, parabens, and phthalates with childhood lung function: Exploring the mediating role of peripheral immune responses.

The functioning of the respiratory system can be interfered with by exposure to mixtures of environmental chemicals, however, the evidence is still ambiguous. We evaluated the association of exposure to mixtures of 14 chemicals, including 2 phenols, 2 parabens, and 10 phthalates, with four major lung function metrics. Based on data from the National Health and Nutrition Examination Survey 2007-2012, this analysis was conducted among 1462 children aged 6-19 years. Linear regression, Bayesian kernel machine regression, quantile-based g-computation regression, and a generalized additive model were performed to estimate the associations. Mediation analyses were performed to investigate plausible biological pathways mediated by immune cells. Our results indicated that the phenols, parabens, and phthalates mixture was negatively related to lung function parameters. And BPA and PP were identified as important contributors to negative associations with FEV1, FVC, and PEF, with non-linear relationships observed between BPA and those outcomes. The most influential factor for a probable FEF25-75 % decline was MCNP. BPA, and MCNP had an interaction effect on FEF25-75 %. The association of PP with FVC and FEV1 has been postulated to be mediated by neutrophils and monocytes. The findings offer insights into the associations of chemical mixtures with respiratory health and the possible driving mechanism, which would be of significance in adding novel evidence of the role of peripheral immune responses, as well as calling for remediation actions to be prioritized during childhood.