Prenatal and lifetime exposure to pesticides and particulate matter and respiratory health in young adults from the CHAMACOS birth

摘要 在美国，目前有2270万人患有哮喘，估计给社会带来了巨大的成本 的身价为10亿美元。环境暴露已被确认在哮喘的病因和肺部中起作用。 功能发育及其与空气污染暴露的关系在更多的城市地区得到了很好的确立。农药 暴露也与哮喘和工人肺功能下降有关。在健康中心 对Salinas母亲和孩子的评估(CHAMACOS)研究，一项对拉丁裔农场工人的纵向研究 在加利福尼亚州萨利纳斯的家庭中，我们观察到早期接触几种杀虫剂，通过测量 生物标志物或居民区靠近农业用途与儿童哮喘和肺功能较差有关。 这些关系是否会持续到成年还不得而知。很少有研究考察过 接触颗粒物和杀虫剂等污染物混合物的影响。来自中国的DNA甲基化 鼻细胞与哮喘和呼吸道炎症有关，而且有证据表明差异甲基化。 与接触污染物有关，这表明环境暴露与呼吸健康之间可能存在联系。 我们研究的长期目标是找出与新生儿呼吸健康相关的可改变因素。 已经成年的一群人。我们将利用CHAMACOS独特的预期出生队列 研究以解决这些问题。参与者目前21岁，500名参与者仍住在附近 萨利纳斯山谷，250名儿童在7岁时完成了肺功能测试。我们在这项建议中的目标是 为了确定早期接触杀虫剂是否会继续影响他们成年后的呼吸健康， 确定农药和空气污染暴露的相对重要性、敏感期(产前、早期 生命和童年/青春期)，改变这些关系的因素和涉及 鼻细胞的甲基化。我们假设，在生命早期接触更多的杀虫剂和空气污染物将 导致较差的呼吸道健康，DNA甲基化将是这些关系的生物标记物。我们会 在22岁进行肺活量测试，并利用加州独特的农药使用情况估计农药暴露情况 报告产前、早期生活(0-3岁)、儿童/青春期(4-20岁)和最近(前一年)的数据。 我们将通过遥感和空气监测相结合的方法估计暴露在颗粒物空气污染中的量 数据。我们将测量从鼻拭子中收集的DNA的甲基化。我们将评估协会是否 在CHAMACOS队列中观察到的7岁时接触杀虫剂与呼吸健康之间的关系一直持续到早期 并确定接触杀虫剂和颗粒物混合物与 呼吸道症状、哮喘、过敏和肺功能。我们将描述DNA甲基化之间的联系 与环境暴露和呼吸健康有关。在这项研究中，我们希望确定最重要的 与不利的呼吸道健康有关的暴露和暴露时间。我们的发现将有助于向未来 与农药使用和空气质量有关的政策，旨在保护呼吸健康。

Abstract In the U.S., there are currently 22.7 million people living with asthma with a large cost to society estimated at $89 billion. Environmental exposures have been identified as playing a role in asthma etiology and lung function growth and the relationship with air pollution exposure is well established in more urban areas. Pesticide exposure has also been related to asthma and decline in lung function in workers. In the Center for the Health Assessment of Mothers And Children Of Salinas (CHAMACOS) Study, a longitudinal study of Latino farmworker families in Salinas California, we observed that early life exposure to several pesticides, as measured by biomarkers or residential proximity to agricultural use, were associated with childhood asthma and poorer lung function at age 7. It is unknown if these relationships persist into adulthood. Few studies have examined the impact of exposure to mixtures of pollutants such as particulate matter and pesticides. Methylation of DNA from nasal cells has been related to asthma and airway inflammation and there is evidence of differential methylation with exposure to pollutants, suggesting a possible link between environmental exposures and respiratory health. The long-term goal of our research is to identify modifiable factors related to respiratory health in a birth cohort that has reached young adulthood. We will leverage the unique CHAMACOS prospective birth cohort study to address these questions. Participants are currently 21 years of age and 500 participants still live near the Salinas Valley, and 250 completed lung function testing at 7 years of age. Our objectives in this proposal are to determine whether early life exposure to pesticides continue to impact their respiratory health in adulthood, identify the relative importance of pesticide and air pollution exposures, periods of susceptibility (prenatal, early life and childhood/adolescence), factors that modify these relationships and potential mechanisms involving the methylation of nasal cells. We hypothesize that higher exposure to pesticides and air pollutants in early life will result in poorer respiratory health and that DNA methylation will be a biomarker of these relationships. We will conduct spirometry testing at 22y and estimate pesticide exposure using California’s unique Pesticide Use Report data for the prenatal, early life (0-3y), childhood/adolescence (4-20y) and recent (previous year) periods. We will estimate exposure to particulate matter air pollution by combining remote sensing and air monitoring data. We will measure methylation in DNA collected from nasal swabs. We will assess whether associations observed in the CHAMACOS cohort between pesticide exposure and respiratory health at 7y persist into early adulthood and determine associations of exposure to a mixture of pesticides and particulate matter with respiratory symptoms, asthma, allergy, and lung function. We will characterize associations of DNA methylation with environmental exposures and respiratory health. In this study, we expect to identify the most important exposures and periods of exposure related to adverse respiratory health. Our findings will help inform future policies related to pesticide use and air quality designed to protect respiratory health.