Childhood and In utero Exposure to Organophosphate and Replacement Brominated Flame Retardants and Child Respiratory Outcomes

项目摘要 由于环境和健康问题，以前用作火焰的多溴联苯醚（PBDEs） 从2004年开始，美国逐步淘汰了阻燃剂，代之以有机磷酸盐（OPFR）， 替代溴化阻燃剂（RBFR）。吸入受污染的房屋灰尘和蒸汽作为一种途径 暴露于这些化学品引起了人们对呼吸系统健康的担忧，因为它们能够引起刺激， 氧化应激、支气管收缩、内分泌干扰和表观遗传变化。然而，这些协会 暴露与呼吸系统结局的关系尚不清楚，特别是在儿童中，由于较高的呼吸系统疾病风险较高， 暴露在化学品中。这个项目的目标是检验儿童期和子宫内暴露于 OPFR和RBFR与呼吸道症状和肺功能受损有关。我们将使用 健康结果和环境措施（HOME）研究，一项多种族妊娠和出生队列研究 来自大辛辛那提，俄亥俄州，环境暴露与美国全国平均水平相似。的接触会 包括在1岁儿童和妊娠20周产前测量的粉尘OPFR和RBFR 作为前3年每年以及妊娠16周和26周产前测量的尿OPFR酯 在交付。呼吸结局将包括每半年评估一次的症状，直至5岁，并强制 在4岁和5岁时测量的1秒呼气量（FEV 1）。脐带血DNA甲基化 使用Illumina Infinium MethylationEPIC BeadChip阵列分析。三个具体目标来检验我们的假设 将确定1）儿童期和子宫内暴露于OPFR和RBFR与不良反应之间的关系， 呼吸结果; 2）OPFR和RBFR相互作用和混合物与不良反应的相关性 产前和产后暴露的呼吸结果; 3）脐带血DNA甲基化变化 产前OPFR和RBFR与儿童呼吸结果相关。这一创新项目 这将是第一个关于阻燃剂和呼吸系统健康的前瞻性研究，包括RBFR，产前暴露， 评估和肺功能的客观测量。完成后，我们将确定更换 阻燃剂，单独或混合物，与不良呼吸结果有关。我们还将 确定了呼吸道风险增加的暴露临界值、易感性窗口和DNA 甲基化改变介导的协会。

PROJECT SUMMARY Due to environmental and health concerns, polybrominated diphenyl ethers (PBDEs) previously used as flame retardants were phased out in the U.S. starting 2004 and substituted with organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs). Inhalation of contaminated house dust and vapor as a route of exposure to these chemicals has raised concerns for respiratory health due to their ability to cause irritation, oxidative stress, bronchoconstriction, endocrine disruption, and epigenetic changes. Yet, the association of these exposures with respiratory outcomes is unknown, especially in children who may be at higher risk due to higher exposure to the chemicals. The goal of this project is to test the hypothesis that childhood and in utero exposure to OPFRs and RBFRs is associated with respiratory symptoms and impaired lung function. We will use the Health Outcomes and Measures of the Environment (HOME) Study, a multiethnic pregnancy and birth cohort from the Greater Cincinnati, Ohio, with environmental exposures similar to U.S. national averages. Exposure will include dust OPFRs and RBFRs measured at child age 1 year and prenatally at 20 weeks of gestation as well as urine OPFR esters measured annually for the first 3 years and prenatally at 16 and 26 weeks of gestation and at delivery. Respiratory outcomes will include symptoms assessed biannually until age 5 years and forced expiratory volume in 1 second (FEV1) measured at ages 4 and 5 years. DNA methylation of cord-blood was profiled using the Illumina Infinium MethylationEPIC BeadChip array. The 3 specific aims to test our hypothesis will be to determine 1) the association of childhood and in utero exposure to OPFRs and RBFRs with adverse respiratory outcomes; 2) the association of OPFRs and RBFRs interactions and mixtures with adverse respiratory outcomes for prenatal and postnatal exposures; and 3) the cord blood DNA methylation changes related to prenatal OPFRs and RBFRs associated with children’s respiratory outcomes. This innovative project will be the first prospective study on flame retardants and respiratory health to include RBFRs, prenatal exposure assessments, and objective measures of lung function. Upon completion, we will have identified the replacement flame retardants, alone or in mixtures, associated with adverse respiratory outcome. We will have also determined the exposure cut-offs for increased respiratory risk, the windows of susceptibility, and the DNA methylation changes mediating the associations.