Relating Diesel Exhaust Exposure to Respiratory and Immune Outcomes in Early Life

将柴油机尾气暴露与生命早期的呼吸和免疫结果联系起来

• 批准号: 8519137
• 负责人: Paloma I Beamer
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-16 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8519137
• 关键词: Address; Age; Air Pollution; Allergens; Allergic; Arizona; Asthma; Biomedical Research; Biometry; Birth; Chemistry; Child; Childhood; Chronic Disease; Clinical; Cohort Studies; Communities; Data; Development; Development Plans; Diesel Exhaust; Disease; Engineering; Enrollment; Environment; Environmental Engineering technology; Environmental Epidemiology; Environmental Exposure; Environmental Irritants; Environmental Pollutants; Epidemiologic Studies; Epidemiology; Evaluation; Exposure to; Foundations; Future; Geographic Information Systems; Goals; Human; IgE; Immune; Immune response; Immune system; Immunotoxicology; Incidence; Infant; Inflammatory; Intervention; Investigation; Journals; Laboratory Study; Lead; Life; Link; Lung; Lung diseases; Measures; Mentors; Mentorship; Modeling; Natural History; Nursery Schools; Outcome; Participant; Peer Review; Phenotype; Physics; Pollution; Positioning Attribute; Prevalence; Primary Prevention; Production; Prospective Studies; Publishing; Research; Research Personnel; Research Project Grants; Respiratory Center; Respiratory System; Respiratory physiology; Risk; Risk Factors; Role; Science; Scientist; Source; Symptoms; Techniques; Testing; Time; Training; Underserved Population; Virus Diseases; Vulnerable Populations; Wheezing; airway inflammation; base; career; career development; case control; chemokine; cohort; community setting; cytokine; design; disease natural history; early childhood; exhaust; experience; immune function; in vivo; infancy; inflammatory marker; meetings; novel; pollutant; programs; prospective; respiratory; skin prick test; therapy development

DESCRIPTION (provided by applicant): Relating Diesel Exhaust Exposure to Respiratory and Immune Outcomes in Early Life The goal of this career development plan is to help Dr. Paloma Beamer, an environmental engineer, launch an independent biomedical research program. Asthma is a heterogeneous disease and the natural history, risk factors and clinical expression of the disease differ between asthma and wheezing phenotypes. Common to all forms of asthma is intermittent or persistent airway inflammation during critical time periods of development as a result of altered immune responses to viral infection, allergic sensitization, or environmental irritants. Vehicle exhaust is the primary source of air pollution in urban environments, where asthma prevalence rates are highest. Exposure to diesel exhaust has been associated with respiratory outcomes including asthma and decreased lung function in epidemiological studies and has also been linked with airway inflammation via in vivo human laboratory studies. The main objective of the research plan is to assess longitudinally the role of diesel-related pollutant exposure during infancy in developmental alterations of the immune and respiratory systems that lead to transient early life wheezing or asthma. The proposed project will use data collected from two on-going prospective birth cohort studies that provide extensive longitudinal data for 1730 children on IgE, cytokines, lung function and respiratory symptoms. To complete the aims, Dr. Beamer will use GIS techniques to model diesel-related pollution exposure based on birth and childhood addresses. She will then assess if diesel-related pollutant exposure in early life is associated with: (1) increased incidence of asthma-related respiratory symptoms; (2) decreased lung function; (3) increased bronchial responsiveness; (4) predominance of Th2 versus Th1 cytokine production and (5) increased allergic sensitization as measured by total and allergen-specific IgE and skin prick tests. Findings from these analyses will aid Dr. Beamer in designing age- appropriate interventions that she can evaluate in future community-based trials aimed at the primary prevention of asthma. This research plan forms the basis of a 5-year career development plan for Dr. Beamer under the mentorship of Dr. Fernando Martinez (respiratory diseases, epidemiology), Dr. Lynn Gerald (asthma, community-based research), Dr. Duane Sherrill (biostatistics), and Dr. Eric Betterton (atmospheric chemistry and physics). Additional collaborators include Dr. Anne Wright (asthma epidemiology) and Dr. Andrew Comrie (urban air pollution, spatial analysis). This interdisciplinary group has designed a career development program that includes (1) formal training in biostatistics, epidemiology, immunotoxicology, spatial analysis, intervention development and evaluation, (2) regular meetings with mentors and collaborators, (3) participation in seminars, (4) presenting results at scientific meetings, (5) publishing in peer-reviewed journals, and (6) submitting an R01. Completion of this career development plan will establish Dr. Beamer as a researcher at the interface of environmental engineering and epidemiology, and position her to design and evaluate novel interventions aimed at reducing the burden of respiratory disease from environmental exposures.

职业发展计划的目标是帮助环境工程师Paloma Beamer博士启动一项独立的生物医学研究计划。哮喘是一种异质性疾病，哮喘和喘息型的自然病史、危险因素和临床表现不同。所有形式的哮喘的共同之处是，由于对病毒感染、过敏反应或环境刺激物的免疫反应改变，在发育的关键时期出现间歇性或持续性的呼吸道炎症。汽车尾气是城市环境空气污染的主要来源，那里的哮喘患病率最高。在流行病学研究中，接触柴油废气与包括哮喘和肺功能下降在内的呼吸结果有关，通过活体人体实验室研究，也与呼吸道炎症有关。该研究计划的主要目标是纵向评估婴儿期与柴油有关的污染物暴露在免疫和呼吸系统发育变化中的作用，这些变化会导致短暂的早期喘息或哮喘。拟议的项目将使用从两项正在进行的前瞻性出生队列研究中收集的数据，这两项研究提供了1730名儿童关于IgE、细胞因子、肺功能和呼吸道症状的广泛纵向数据。为了实现这些目标，比默博士将使用地理信息系统技术，根据出生和童年住址对与柴油相关的污染暴露进行建模。然后，她将评估早期接触柴油相关污染物是否与以下因素有关：(1)哮喘相关呼吸道症状的发生率增加；(2)肺功能下降；(3)支气管反应性增强；(4)Th2相对于Th1细胞因子的产生占优势；(5)通过总和过敏原特异性IgE和皮肤点刺试验衡量，过敏反应增加。这些分析的结果将有助于比默博士设计适合年龄的干预措施，她可以在未来旨在哮喘一级预防的社区试验中进行评估。这项研究计划构成了Beamer博士在Fernando Martinez博士(呼吸系统疾病，流行病学)、Lynn Gerald博士(哮喘，社区研究)、Duane Sherrill博士(生物统计学)和Eric Betterton博士(大气化学和物理)的指导下的五年职业发展计划的基础。其他合作者包括Anne Wright博士(哮喘流行病学)和Andrew Comrie博士(城市空气污染，空间分析)。这个跨学科小组设计了一个职业发展计划，其中包括(1)生物统计学、流行病学、免疫毒理学、空间分析、干预发展和评估方面的正式培训，(2)与导师和合作者的定期会议，(3)参加研讨会，(4)在科学会议上展示结果，(5)在同行评议期刊上发表文章，以及(6)提交R01。这一职业发展计划的完成将使比默博士成为环境工程和流行病学领域的研究人员，并使她能够设计和评估旨在减轻环境暴露造成的呼吸道疾病负担的新型干预措施。