Early life exposure to metal mixtures: impacts on asthma and lungdevelopment

生命早期接触金属混合物：对哮喘和肺部发育的影响

基本信息

批准号：
10678307
负责人：
Ruwan Thilakaratne
金额：
$ 4.48万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10678307
关键词：
Address Adult Affect Air Allergens Allergic American Animals Area Asthma Biological Markers Birth Blood California Child Child Health Childhood Childhood Asthma Chronic Disease Chronic Obstructive Pulmonary Disease Collaborations Competence Complement Data Development Developmental Process Diagnosis Diet Educational workshop Ensure Environment Environmental Epidemiology Environmental Health Erythrocytes Evaluation Exposure to Extrinsic asthma Faculty Fellowship First Pregnancy Trimester Forced expiratory volume function Future Growth Health Health Expenditures Housing Hypersensitivity IgE Immediate hypersensitivity Immune Immune system Individual Intervention Investments Joints Knowledge Lead Life Life Cycle Stages Link Lung Massachusetts Measures Mediating Mediation Mentors Metal exposure Metals Methods Morbidity - disease rate Mothers Outcome Oxidative Stress Pathogenesis Pathology Pathway interactions Perinatal Epidemiology Perinatal Exposure Prevention strategy Productivity Public Health Pulmonary Pathology Recommendation Research Research Personnel Resources Risk Role Scientist Serum Shapes Source Spirometry Statistical Computing Systems Development Time Toxicology Training Universities Water Work Writing Zinc airborne allergen career development cohort cost dietary early childhood early life exposure early pregnancy epidemiology study epigenome exposed human population immune function improved in utero innovation insight lung development lung health meetings neurodevelopment novel postnatal prenatal prenatal exposure protective effect public health priorities pulmonary function recruit respiratory health respiratory morbidity symposium

项目摘要

PROJECT SUMMARY Pediatric asthma is a major burden on child health, affecting 7% of American children (6 million children) annually. Additionally, lung function in childhood is highly predictive of adult pulmonary morbidity. In utero and early childhood exposure to metals, both essential (beneficial for health) and non-essential (harmful to health), may shape respiratory health. Toxicologic evidence suggests prenatal and early childhood exposure to non- essential metals causes oxidative stress, which disrupts normal immune system development and alters the epigenome, a strong determinant of immune and lung development. The ubiquity of metals in the maternal and child environments, and their modifiable sources in water, air, diet, and housing, imply potentially large public health impacts. However, the few existing studies examining these associations have limitations: almost all analyze metals individually rather than as a mixture, and consider only a single timepoint of exposure. The proposed research utilizes data from Project Viva, a large, well-characterized pre-birth cohort of 2,128 mother- child pairs recruited between 1999-2002 in eastern Massachusetts, to address these gaps. The proposed research will assess impacts of metal mixture exposure in the first trimester and early childhood on: (1) blood levels of total and allergen-specific immunoglobulin E (IgE) in early childhood, biomarkers of allergic sensitization; (2) prevalent asthma in mid-childhood, and mediation of prenatal metal effects by early childhood IgE; and (3) lung function in mid-childhood. The proposed research overcomes the limitations of prior work by analyzing 14 metals jointly rather than individually, and distinguishing contributions of metal exposure in early pregnancy vs. early childhood to immune system and lung pathology. Overall, this research will provide evidence for interventions, such as dietary recommendations, to modulate metal exposure in order to promote respiratory health, and suggest optimal time windows for such interventions. The training plan for the Fellowship applicant was developed in collaboration with the sponsorship team, including Dr. Alan Hubbard (sponsor), Dr. John Balmes (co-sponsor), and Dr. Andres Cardenas (co-sponsor), and centers on competency in causal inference, the analysis of exposure mixtures, and subject area knowledge in children’s environmental health, such as toxicology, asthma, and perinatal epidemiology. Coursework in these areas is enriched by attendance to conferences, trainings, and workshops. Regular meetings with individual sponsors and the sponsorship team as a whole will further facilitate training. The environment at the University of California, Berkeley is highly supportive of this training, providing access to a diverse array of faculty and research collaborations in environmental epidemiology, and abundant resources in statistical computing, scientific writing, career development, mentoring, and advising. Overall, the training plan and environment will ensure the applicant matures into a productive and innovative researcher in children’s environmental health.

项目概要小儿哮喘是儿童健康的主要负担，影响 7% 的美国儿童（600 万儿童）此外，儿童时期的肺功能可以高度预测成人子宫内和成人期间的肺部发病率。儿童早期接触金属，包括必需的（有益于健康）和非必需的（有害健康），毒理学证据表明，产前和儿童早期接触非物质可能会影响呼吸系统健康。必需金属会引起氧化应激，从而破坏正常的免疫系统发育并改变表观基因组，免疫和肺部发育的重要决定因素金属在母体和肺部的普遍存在。儿童环境及其可改变的水、空气、饮食和住房来源，潜在的大型公共场所然而，现有的少数几项研究这些关联的研究都存在局限性：几乎所有研究都存在局限性。单独分析金属而不是混合物，并仅考虑单个暴露时间点。拟议的研究利用了 Viva 项目的数据，该项目是一个由 2,128 名母亲组成的大型、特征明确的产前队列—— 1999 年至 2002 年期间在马萨诸塞州东部招募了一对儿童，以解决这些差距。研究将评估孕早期和幼儿期接触金属混合物对以下方面的影响：(1) 血液儿童早期总免疫球蛋白 E 和过敏原特异性免疫球蛋白 E (IgE) 的水平，过敏的生物标志物 (2) 儿童中期哮喘的流行以及儿童早期对产前金属效应的调节 IgE；(3) 儿童中期的肺功能本研究克服了先前工作的局限性。 14 种金属联合分析而不是单独分析，并区分早期金属暴露的贡献总的来说，这项研究将为免疫系统和肺部病理学提供证据。采取干预措施，例如饮食建议，调节金属暴露以促进呼吸健康状况，并建议此类干预措施的最佳时间窗口奖学金申请人的培训计划。是与赞助团队合作开发的，包括 Alan Hubbard 博士（赞助商）、John 博士 Balmes（共同发起人）和 Andres Cardenas 博士（共同发起人），重点关注因果推理能力，接触混合物的分析以及儿童环境健康的学科领域知识，例如通过参加毒理学、哮喘和围产期流行病学，这些领域的课程内容得到了丰富。与个人赞助商和赞助团队定期举行会议、培训和研讨会。加州大学伯克利分校的整体环境将进一步促进培训。该培训的目的是提供环境方面各种教师和研究合作的机会流行病学，以及统计计算、科学写作、职业发展、指导等方面的丰富资源，总体而言，培训计划和环境将确保申请人成熟并富有成效。儿童环境健康方面的创新研究人员。