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

这个职业发展计划的目标是帮助Paloma Beamer博士，一位环境工程师，启动一个独立的生物医学研究项目。哮喘是一种异质性疾病，哮喘和喘息表型之间的自然病史、危险因素和临床表现存在差异。所有形式哮喘的共同特点是，在发育的关键时期，由于对病毒感染、过敏致敏或环境刺激物的免疫反应改变，出现间歇性或持续性气道炎症。在哮喘患病率最高的城市环境中，汽车尾气是空气污染的主要来源。在流行病学研究中，暴露于柴油废气与呼吸系统疾病有关，包括哮喘和肺功能下降，在人体实验室研究中也与气道炎症有关。研究计划的主要目的是纵向评估婴儿时期柴油相关污染物暴露在导致早期短暂喘息或哮喘的免疫和呼吸系统发育改变中的作用。拟议的项目将使用从两个正在进行的前瞻性出生队列研究收集的数据，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技术来模拟基于出生和童年地址的柴油相关污染暴露。然后，她将评估生命早期与柴油相关的污染物暴露是否与：(1)哮喘相关呼吸道症状的发生率增加有关；(2)肺功能下降；(3)支气管反应性增高；(4) Th2与Th1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致敏性增加。这些分析的发现将帮助Beamer博士设计适合年龄的干预措施，她可以在未来以社区为基础的哮喘初级预防试验中进行评估。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，该研究计划构成了Beamer博士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)在生物统计学、流行病学、免疫毒理学、空间分析、干预开发和评估方面的正式培训，(2)与导师和合作者定期会面，(3)参加研讨会，(4)在科学会议上展示成果，(5)在同行评审的期刊上发表文章，(6)提交R01。该职业发展计划的完成将使Beamer博士成为环境工程和流行病学界面的研究员，并使她能够设计和评估旨在减少环境暴露引起的呼吸系统疾病负担的新干预措施。

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.