The 2020 ESPINA study follow-up Exam: Fungicides, Insecticides, Inflammation and Child Development

在过去的20年里，农业杀虫剂的销量稳步上升，杀菌剂的使用也在稳步上升 在过去的十年里飞涨。不幸的是，对儿童发育毒性的直接评估 与常用杀菌剂，如唑类或喹酮类体外抑制剂(QOI)的关系不可用 因为它们在生物标本中的量化方法直到最近才被开发出来。处于实验阶段 研究，暴露QOI杀菌剂，导致与神经炎症相关的表观遗传变化，以及更高 自由基的水平。另一种常用的杀菌剂，氮唑类，也与肝脏有关。 体外炎症和毒性。唑类杀菌剂与用于 临床实践中，高达20%的患者与肝酶升高有关。 接触胆碱酯酶抑制剂杀虫剂与短期和长期相关 相关儿童的神经行为/认知延迟。是否持续暴露于有机磷 或其他杀虫剂，如新烟碱或拟除虫菊酯，是否会影响青春期的认知尚不清楚。 我们建议对青少年参与者(16-21岁，n=)进行跟踪调查 2020年儿童和青少年次级农药暴露(ESPINA)研究。这是美国国立卫生研究院资助的 这项研究自2008年以来对厄瓜多尔佩德罗·蒙卡约县的参与者进行了调查。佩德罗·蒙卡约有一个 是美洲最密集的花卉种植园。花卉的生产涉及到一个 杀菌剂使用量过高。我们计划评估持续和长期的 农药暴露与神经认知和炎症标记物(全身、神经和肝脏)有关。致我们的 知识，这将是第一个评估#年健康结果的儿童/青少年流行病学研究 与杀菌剂和新烟碱暴露的关系。这项前瞻性研究利用了现有的血液 2016年的杀虫剂和2008年和2016年的乙酰胆碱酯酶的测量。 具体目标是检验以下假设：2016年杀虫剂的尿代谢物 和2020年(有机磷、新烟碱、拟除虫菊酯)和2016年的杀菌剂(氮唑、QOI)相关 具有：1)更高的全身和神经炎症亚临床标志物(CRP、TNF、IL-6、sICAM-1、sVCAM-1、 Mcp-1、sCD14、sCD163)；2)杀虫剂，特别是唑类杀菌剂与 肝脏炎症标志物：转氨酶(AST和ALT)和细胞角蛋白18。 2016-2018年与所有炎症标志物的前瞻性关联；3)较低的神经认知能力 在青春期。我们将测试杀菌剂和杀虫剂与神经认知的纵向关联 性能，并将对比这些发现在杀虫剂，以评估神经毒性效力。4)作为 探索性目标：我们将评估炎症对农药所致损害的中介或调节作用。 神经行为表现。

The sales of agricultural insecticides have steadily risen in the last 20 years and the use of fungicides have skyrocketed in the last decade. Unfortunately, direct assessments of children's developmental toxicity in relation to commonly used fungicides such as Azoles or Quinone Outside Inhibitors (QoI) are unavailable because methods for their quantification in bio-specimens have only recently been developed. In experimental studies, exposures QoI fungicides, resulted in epigenetic changes related to neuro-inflammation, and higher levels of free-radicals. Azoles, another heavily used fungicide class, have also been linked with liver inflammation and toxicity in-vitro. Azole fungicides share the same structure as azole antifungals used in clinical practice, which are associated with elevations of liver enzymes in up to 20% of patients. Cholinesterase inhibitor insecticide exposures have been associated with short- and long-lasting neurobehavioral/cognitive delays in children associated. Whether continuing exposures to organophosphates or other insecticides such as neonicotinoids or pyrethroids can affect cognition in adolescence is unclear. We propose to conduct a follow-up investigation of adolescent participants (ages 16-21 y, n=535) of the Secondary Pesticide Exposure among Children and Adolescents (ESPINA) study in 2020. This NIH-funded study has examined participants in Pedro Moncayo County, Ecuador since 2008. Pedro Moncayo has one of the highest concentrations of flower plantations in the Americas. The production of flowers involves a disproportionately high use of fungicides. We plan to assess the ongoing and long-term associations of pesticide exposures with neurocognition, and inflammatory markers (systemic, neuro and liver). To our knowledge, this will be the first epidemiologic study of children/adolescents to evaluate health outcomes in relation to fungicide and neonicotinoid exposures. This prospective study capitalizes on existing blood measurements of insecticides in 2016 and acetylcholinesterase in 2008 and 2016. The specific aims are to test the following hypotheses: Urinary metabolites of insecticides in 2016 and 2020 (organophosphates, neonicotinoids, pyrethroids) and fungicides (Azoles, QoI) in 2016 are associated with: 1) higher subclinical markers of systemic and neuro inflammation (CRP, TNF, IL-6, sICAM-1, sVCAM-1, MCP-1, sCD14, sCD163); 2) Pesticides, particularly azole fungicides are associated with subclinical increases in liver inflammation markers: transaminases (AST and ALT) and cytokeratin 18. We will test concurrent and prospective associations with all inflammation markers in 2016-2018; 3) lower neur0-cognitive performance in adolescence. We will test longitudinal associations of fungicides and insecticides with neurocognitive performance, and will contrast such findings across pesticides to evaluate neurotoxic potencies. 4) As an exploratory aim: we will assess mediating or modifying effects of inflammation on pesticide-induced impaired neurobehavioral performance.