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

家庭空气污染、炎症以及对孕妇和婴儿血红蛋白浓度的影响

• 批准号: 10650731
• 负责人: Sheela Selin Sinharoy
• 金额: $ 23.47万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10650731
• 关键词: Address; Adherence; Affect; Age; Air Pollutants; Air Pollution; Anemia; Anemia due to Chronic Disorder; Behavior; Biological; Biological Markers; Biological Process; Biomass; Blinded; Blood; C-reactive protein; Carbon; Carbon Black; Carbon Monoxide; Carrying Capacities; Child; Child Development; Coal; Cookstove; Country; Creativeness; Data; Data Collection; Development; Disease; Dryness; Enrollment; Environmental Exposure; Environmental Health; Exposure to; Fostering; Future; Gases; Goals; Guatemala; Health; Hemoglobin; Hour; Household Air Pollution; Impairment; India; Infant; Inflammation; Interleukin-6; Intervention; Laboratories; Life; Link; Low Birth Weight Infant; Maternal and Child Health; Mediation; Mediator; Metabolic; Methods; Mission; Modeling; Mothers; Outcome; Oxygen; Participant; Pathway Analysis; Pathway interactions; Pattern; Persons; Peru; Petroleum; Physiological; Pneumonia; Policies; Policy Maker; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Public Health; Randomized, Controlled Trials; Research; Resolution; Risk Factors; Role; Rural; Rwanda; Sampling; Science; Signal Transduction; Site; Solid; Spottings; Study Subject; Surveys; Testing; Time; United States National Institutes of Health; Vulnerable Populations; Woman; Wood material; Work; World Health Organization; biological systems; biomarker panel; burden of illness; cooking; critical period; demographics; fine particles; improved; infancy; innovation; iron absorption; metabolomics; novel marker; pollutant; post intervention; primary outcome; programs; reproductive; secondary outcome; solid fuel; wasting

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.

项目概要/摘要 家庭空气污染 (HAP) 是疾病的主要危险因素，尤其是对近 30 亿人来说 全世界主要使用固体燃料（例如木材、煤炭、农作物废料）进行烹饪的人。同时，贫血 影响全球 6.13 亿（33%）育龄妇女和 2.7 亿（42%）五岁以下儿童。这 拟议项目的长期目标是加强科学证据和方案的合理性， 通过结合以下假设来解决家庭空气污染和贫血问题的政策和研究： 驱动和发现科学。该应用程序的总体目标是通过以下方式定义生物机制： 哪些家庭空气污染可能影响血红蛋白浓度并确定相关的新型生物标志物 与暴露和血红蛋白浓度有关。中心假设是多种生物途径 同时和相反的方向运作，可能掩盖重要的生理关系。 中心假设将通过追求两个具体目标来检验：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 加入家庭空气污染干预网络的孕妇和婴儿的浓度 (HAPIN) 试验； 2) 在婴儿子集中，确定空气污染物与空气污染物之间关联的新生物标志物 血红蛋白，使用非靶向代谢组学和代谢扰动的中介分析。这两个目标都将 使用从危地马拉农村 HAPIN 试验地点的参与者收集的现有干血斑 (DBS)。在下面 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 几个月）将对一组炎症生物标志物进行检测。结果数据将与 单独中介模型中参与者的暴露和血红蛋白浓度的现有数据 孕妇和婴儿，检查潜在的影响途径。第二个目标是对 100 名婴儿进行 DBS （6 个月大）将使用非目标高分辨率代谢组学工作流程进行分析，并得到结果数据 将分析代谢信号、特定污染物暴露和血红蛋白之间的关联 浓度。第二个目标还将涉及探索性中介分析，以检查之间的模式 使用“中间相遇”框架来评估暴露、代谢组学扰动和血红蛋白浓度 方法。本申请中提出的研究具有创新性，因为它使用了严格的前沿技术 利用现有数据、样本和 HAPIN 试验中已完成的多年工作的方法， 产生与家庭空气污染与生物机制相关的新证据和发现 贫血。拟议的研究意义重大，因为它有望为以下问题提供有说服力的新论据： 政策制定者提倡和补贴清洁烹饪，减少家庭空气污染以及 弱势人群贫血流行率，特别是在怀孕和产后的关键时期 生命的第一年。