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.

项目摘要儿科哮喘是儿童健康的重大烧伤，影响了7％的美国儿童（600万儿童）在子宫内，此外，儿童期的肺功能高度预测了成人肺部发病率。儿童早期接触金属，无论是必不可少的（对健康有益）和不必要的（对健康有害），可能会塑造呼吸健康。毒理学证据表明产前和幼儿暴露于非 - 基本金属会导致氧化应激，这破坏了正常的免疫系统发育并改变表观基因组，是免疫和肺发育的强大决定因素。孕产妇中金属的无处不在儿童环境及其在水，空气，饮食和住房中可修改的来源，这意味着潜在的大型公众健康影响。但是，少数研究这些关联的现有研究有局限性：几乎全部单独分析金属而不是作为混合物，并仅考虑一次暴露时间点。这拟议的研究利用了Viva项目的数据，Viva是一个大型，特征良好的出生前队列，为2,128个母亲儿童对在1999年至2002年在马萨诸塞州东部招募，以解决这些差距。提议研究将评估孕期金属混合物暴露的影响：（1）血液幼儿期的总和特异性免疫球蛋白E（IgE）的水平，过敏症的生物标志物敏化；（2）年龄中期流行的哮喘，以及幼年时期产前金属效应的调解 ige; （3）肺部功能在中期。拟议的研究克服了先前工作的局限共同分析14种金属而不是单独分析，并在早期区分金属暴露的贡献怀孕与幼儿期至免疫系统和肺病理学。总体而言，这项研究将提供证据为了进行干预措施，例如饮食建议，以调节金属暴露以促进呼吸健康，并建议进行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，包括艾伦·哈伯德（Alan Hubbard）（赞助商），约翰博士 Balmes（共同提案国）和Andres Cardenas博士（共同赞助者），并以因果推断的能力为中心，暴露混合物的分析以及儿童环境健康中的主题领域知识，例如毒理学，哮喘和围产期流行病学。这些领域的课程工作通过出勤而丰富会议，培训和讲习班。与个人赞助商和赞助团队定期会议整体将进一步支持。加州大学伯克利分校的环境得到了高度支持。在这项培训中，提供了在环境中访问一系列教师和研究合作的渠道流行病学和统计计算，科学写作，职业发展，心理发展的丰富资源和咨询。总体而言，培训计划和环境将确保适用的适应为生产力和儿童环境健康的创新研究员。