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

描述（由申请人提供）：柴油废气暴露与呼吸和免疫结果在早期生活这个职业发展计划的目标是帮助博士帕洛玛比默，环境工程师，推出一个独立的生物医学研究计划。哮喘是一种异质性疾病，其自然史、危险因素和临床表现在哮喘和喘息表型之间存在差异。所有形式的哮喘的共同点是在发展的关键时期由于对病毒感染、过敏性致敏或环境刺激物的免疫应答改变而引起的间歇性或持续性气道炎症。汽车尾气是城市环境中空气污染的主要来源，哮喘患病率最高。在流行病学研究中，暴露于柴油机废气与呼吸系统结果（包括哮喘和肺功能下降）相关，并且通过体内人体实验室研究也与气道炎症相关。研究计划的主要目标是纵向评估婴儿期柴油相关污染物暴露在导致短暂性早期喘息或哮喘的免疫和呼吸系统发育变化中的作用。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，这些研究为1730名儿童提供了关于IgE、细胞因子、肺功能和呼吸道症状的广泛纵向数据。为了完成这些目标，Beamer博士将使用GIS技术，根据出生和童年地址来模拟与柴油相关的污染暴露。然后，她将评估生命早期柴油相关污染物暴露是否与以下因素相关：（1）哮喘相关呼吸道症状发生率增加;（2）肺功能下降;（3）支气管反应性增加;（4）Th 2相对于Th 1细胞因子产生的优势;（5）通过总IgE和过敏原特异性IgE和皮肤点刺试验测量的过敏性致敏性增加。这些分析的结果将帮助Beamer博士设计适合年龄的干预措施，她可以在未来的社区试验中评估这些干预措施，以预防哮喘。该研究计划构成了Beamer博士在Fernando Martinez博士（呼吸系统疾病，流行病学），林恩杰拉尔德博士（哮喘，社区研究），Duane Sherrill博士（生物统计学）和Eric Betterton博士（大气化学和物理学）指导下的5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，包括（1）生物统计学，流行病学，免疫毒理学，空间分析，干预开发和评估的正式培训，（2）与导师和合作者定期会议，（3）参加研讨会，（4）在科学会议上展示结果，（5）在同行评议的期刊上发表，以及（6）提交R 01。Beamer博士将成为环境工程和流行病学界面的研究人员，并使她能够设计和评估旨在减少环境暴露呼吸系统疾病负担的新型干预措施。

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.