Household air pollution, inflammation, and effects on hemoglobin concentration among pregnant women and infants

项目总结/摘要 家庭空气污染（HAP）是疾病的主要风险因素，特别是对近30亿人来说 世界各地主要使用固体燃料（如木材，煤炭，作物废料）做饭的人。同时，贫血 影响到全球6.13亿（33%）育龄妇女和2.7亿（42%）五岁以下儿童。的 拟议项目的长期目标是加强项目的科学证据和理由， 政策和研究，以解决家庭空气污染和贫血，通过假设的组合- 驱动和发现科学。本申请的总体目标是通过以下方式定义生物学机制： 哪些家庭空气污染可能影响血红蛋白浓度，并确定与血红蛋白浓度相关的新生物标志物。 暴露程度和血红蛋白浓度核心假设是，多种生物途径 同时和以相反的方向操作，潜在地掩盖了生理上重要的关系。 中心假设将通过追求两个具体目标进行测试：1）确定 干预、暴露（PM2.5、一氧化碳）、炎症生物标志物水平和血红蛋白 家庭空气污染干预网络中登记的孕妇和婴儿的浓度 （HAPIN）试验;和2）在婴儿的一个子集中，确定空气污染物与 血红蛋白，使用非靶向代谢组学和代谢扰动的调解分析。这两个目标将 使用从危地马拉农村HAPIN试验地点的参与者中收集的现有干血斑（DBS）。下 第一个目标是对孕妇（妊娠24-28周）和婴儿（6岁）的DBS进行实验室分析 月）将针对一组炎症生物标志物进行。结果数据将与 关于参与者暴露和血红蛋白浓度的现有数据， 孕妇和婴儿，以检查潜在的影响途径。对于第二个目标，来自100名婴儿的DBS (age 6个月）将使用非靶向高分辨率代谢组学工作流程进行分析， 将分析代谢信号、暴露于特定污染物和血红蛋白之间的关联 浓度的第二个目标还将涉及探索性的中介分析，以检查 暴露、代谢组学扰动和血红蛋白浓度，使用“中间相遇”框架 approach.这项申请中提出的研究具有创新性，因为它使用了严谨、前沿的 利用HAPIN试验中已经完成的现有数据、样本和多年工作的方法， 产生新的证据和发现，与家庭空气污染和 贫血这项研究具有重要意义，因为它有望为以下问题提供一个有说服力的新论据： 政策制定者促进和补贴清洁烹饪，减少家庭空气污染， 弱势群体中的贫血患病率，特别是在怀孕和分娩的关键时期， 生命的第一年。

PROJECT SUMMARY/ABSTRACT Household air pollution (HAP) is a leading risk factor for disease, particularly for the nearly 3 billion people worldwide who primarily use solid fuels (e.g. wood, coal, crop waste) for cooking. At the same time, anemia affects 613 million (33%) women of reproductive age and 270 million (42%) children under age five globally. The long-term goal of the proposed project is to strengthen the scientific evidence and justification for programs, policy, and research to address both household air pollution and anemia, through a combination of hypothesis- driven and discovery science. The overall objective for this application is to define biological mechanisms through which household air pollution may affect hemoglobin concentrations and to identify novel biomarkers associated with exposures and hemoglobin concentration. The central hypothesis is that multiple biological pathways are operating simultaneously and in opposing directions, potentially masking physiologically important relationships. The central hypothesis will be tested by pursuing two specific aims: 1) identify relationships between the intervention, exposures (PM2.5, carbon monoxide), levels of biomarkers of inflammation, and hemoglobin concentrations among pregnant women and infants enrolled in the Household Air Pollution Intervention Network (HAPIN) trial; and 2) in a subset of infants, identify novel biomarkers of associations between air pollutants and hemoglobin, using untargeted metabolomics and mediation analysis of metabolic perturbations. Both aims will use existing dried blood spots (DBS) collected from participants in the HAPIN trial site in rural Guatemala. Under the first aim, laboratory analyses of DBS from pregnant women (24-28 weeks gestation) and infants (age 6 months) will be performed for a panel of biomarkers of inflammation. The resulting data will be combined with existing data on participants’ exposures and hemoglobin concentrations in separate mediation models for pregnant women and infants, to examine potential pathways of effect. For the second aim, DBS from 100 infants (age 6 months) will be analyzed using an untargeted high-resolution metabolomics workflow, and resulting data will be analyzed for associations between metabolic signals, exposures to specific pollutants, and hemoglobin concentrations. The second aim will also involve an exploratory mediation analysis to examine patterns between exposures, metabolomic perturbations, and hemoglobin concentration, using a “meet in the middle” framework approach. The research proposed in this application is innovative because of its use of rigorous, cutting-edge methods that leverage the existing data, samples, and years of work already completed in the HAPIN trial, to generate new evidence and discoveries related to biological mechanisms linking household air pollution and anemia. The proposed research is significant because it is expected to provide a persuasive new argument for policymakers to promote and subsidize clean cooking, to reduce exposure to household air pollution as well as anemia prevalence among vulnerable populations, especially during the critical periods of pregnancy and the first year of life.