Assessment of joint effects of pesticides and air pollution in pediatric asthma

该K22职业发展奖（CDA）的研究目标是确定农业农药暴露是否混淆或改变环境空气污染暴露与哮喘儿童肺功能之间的关系。核心假设是，生命早期暴露于农业农药以及暴露于高水平的环境空气污染与肺功能下降显著相关。儿童期长期接触农药对呼吸系统的影响尚不清楚。由于加州州已经要求全面报告农业农药使用超过二十年，因此可以有效地对哮喘病因的假设关键窗口进行社区水平农药应用的回顾性暴露评估。除了接触农药外，该州主要农业区圣华金河谷的土地使用模式和地形也导致了高水平的环境接触。 空气污染（AAP）。弗雷斯诺哮喘儿童环境研究（FACES）提供了一个特征良好的纵向队列，以调查农药和AAP对肺功能变化和哮喘发展的同时影响。研究方法将包括三个具体目标。(Aim 1）、实施三种农药暴露评估策略（基于地理的暴露、灰尘样本收集和尿液生物标志物收集），以估计与FACES队列中当前肺功能的相关性。我们假设肺功能和农药之间的关系将因暴露评估方法和农药类别而异。我们预计，这些短期暴露措施可以用来校准长期农药暴露估计。(Aim 2）：比较两种贝叶斯统计方法，以了解农药暴露与肺功能之间的关系。这一目标将包括统计模拟，将与农药暴露估计告知目标1和回顾性空气污染数据的基础上，从FACES队列（n = 315）的居住历史进行。将使用两种最近开发的统计方法（非参数贝叶斯收缩和曲线回归）分析肺功能、环境暴露和人口统计学协变量（性别和种族）之间的关系。这个目标的目的是了解这些贝叶斯方法的统计模型性能的研究复杂的环境混合物和人口因素。（三）、农药暴露与环境空气污染联合对肺功能的独立和联合影响的评估。我们将估计幼儿期（0 - 1岁）的影响 在目标2的模型中，暴露于社区水平的农药和环境空气污染物对FACES队列（n=315）基线肺功能的影响。我们假设，儿童早期（0 - 1岁）暴露于三类农药将改变空气中 污染和FEV 1在研究入组时测量（6 - 11岁）。CDA候选人是科罗拉多州立大学（CSU）环境和放射健康科学系流行病学终身助理教授，接受过环境和社会流行病学方面的培训。她的短期职业目标是扩大她目前在哮喘流行病学方面的研究，并制定一项研究计划，以解决脆弱社区的多污染物暴露分析，特别关注农业农药暴露和环境空气污染。她的长期职业目标是了解环境污染物，生物源性暴露和宿主因素对儿童哮喘发病率的动态相互作用。该CDA将支持她在毒理学和贝叶斯统计学方面的教学和经验培训。由于传统统计方法的推理局限性，她为申请这项资助而接受的技能训练是必要的（如广义线性模型）用于多污染物分析（即在施用农药混合物或混合物的情况下评估有毒化合物）和多领域分析（即确定农药在各种相关因素组合中的独立作用，包括人为因素和生物因素）。这些统计方法必须了解化合物在毒理学水平上的相互作用。她的生物统计学培训将包括流行病学研究的数据模拟和贝叶斯方法;毒理学培训将包括课程工作，暴露评估的实地工作，以及环境和生物标志物样本分析的实验室工作。她的部门在环境流行病学，暴露评估和毒理学方面拥有专业知识;校园提供应用统计方法和方法的全面培训。这些经验将为CDA的开展以及未来的跨学科研究环境健康提供信息。该CDA通过调查低水平慢性暴露对健康的影响来支持NIEHS的使命。

DESCRIPTION (provided by applicant): The research objective of this K22 Career Development Award (CDA) is to ascertain if agricultural pesticide exposure confounds or modifies the relation between ambient air pollution exposure and pulmonary function in children with asthma. The central hypothesis is that early-life exposure to agricultural pesticides in conjunction with exposure to high levels of ambient air pollution is associated significantly with decreased lung function. The respiratory effects of chronic exposure to agricultural pesticides in childhood remain unknown. As the State of California has required full reporting of agricultural pesticide use for over two decades, retrospective exposure assessment of community-level pesticide application can be conducted effectively for hypothesized critical windows for asthma etiology. In addition to pesticide exposure, the land use patterns and topography of the San Joaquin Valley, the state's major agricultural region, result in high levels of exposure to ambient air pollution (AAP). The Fresno Asthmatic Children's Environment Study (FACES) offers a well-characterized longitudinal cohort to investigate the simultaneous effects of pesticides and AAP on changes in lung function and development of asthma. The research approach will consist of three Specific Aims. (Aim 1): Implementation of three pesticide exposure assessment strategies (geographic-based exposure, collection of dust samples, and collection of urinary biomarkers) to estimate associations with current lung function in the FACES cohort. We hypothesize that the relation between lung function and pesticides will vary by exposure assessment method and by class of pesticide. We anticipate that these short-term exposure measures can be used to calibrate the long-term pesticide exposures estimates. (Aim 2): Comparison of two Bayesian statistical methods to understand the relation between agricultural pesticide exposure and lung function. This aim will consist of statistical simulations that will be conducted with pesticide exposure estimates informed by Aim 1 and retrospective air pollution data based on residential histories from the FACES cohort (n = 315). The relation between lung function, environmental exposures and demographic covariates (sex and race) will be analyzed using two recently developed statistical methods, nonparametric Bayes shrinkage and profile regression. The objective of this aim is to understand the statistical model performance of these Bayesian approaches for research of complex environmental mixtures and demographic factors. (3). Assessment of the independent and joint effects of pesticide exposure in combination with ambient air pollution on lung function. We will estimate the effect of early childhood (ages 0 - 1) exposure to community-level pesticide and ambient air pollutants on baseline lung function from the FACES cohort (n=315) in a model derived in Aim 2. We hypothesize that early childhood (0 - 1 year) exposure to three classes of agricultural pesticides will modify the relation between air pollution and FEV1 measured at study enrollment (ages 6 - 11). The CDA Candidate is a tenure-track Assistant Professor of Epidemiology in the Department of Environmental and Radiological Health Sciences at Colorado State University (CSU) with training in environmental and social epidemiology. Her short-term career goal is to expand her current research in asthma epidemiology and develop a research program to address multi-pollutant exposure analyses in vulnerable communities, with specific focus on agricultural pesticide exposures and ambient air pollution. Her long-term career goal is to understand the dynamic interaction of environmental pollutants, biogenic exposures, and host factors on asthma incidence in children. This CDA will support her didactic and experiential training in toxicology and Bayesian statistics. Her statisticl training for this grant application is necessitated by the inferential limitations of conventional statistical methods (e.g. generalized linear models) for multi-pollutant analyses (i.e. regarding assessment of toxic compounds given application of mixtures or combinations of pesticides) and multi-domain analyses (i.e. ascertainment of the independent contribution of pesticides among combinations of correlated factors, both anthropogenic and biogenic in nature.) These statistical approaches must be informed by an understanding of compound interaction on a toxicological level. Her biostatistics training will include data simulation and Bayesian approaches for epidemiologic studies; toxicology training will include course work, field work in exposure assessment, and laboratory work in environmental and biomarker sample analysis. Her department has expertise in environmental epidemiology, exposure assessment and toxicology; the campus offers comprehensive training in applied statistical approaches and methods. These experiences will inform the conduct of this CDA, as well as future work transdisciplinary research environmental health. This CDA supports the mission of the NIEHS via investigation of the health effects of low-level chronic exposures.