Indoor environmental exposures and pulmonary inflammation and morbidity in sickle cell anemia

项目总结/摘要 这个指导病人为导向的研究职业发展奖将提供S。Christy Sadreameli医学博士M.H. S 有经验和培训，成为一个独立的研究者在儿科肺病的重点是影响 环境暴露对镰状细胞性贫血（SCA）肺部发病率和炎症的影响。尽管取得了进展， 预防和治疗SCA，受影响的儿童和年轻人继续遭受大量的 肺部发病率，包括急性胸部综合征（ACS）和呼吸道症状，如咳嗽和 气喘在SCA中几乎没有发现可改变的风险因素，但新的数据表明，暴露于SHS和 其他环境因素与肺部发病率有关。室内环境暴露，如二手 吸烟（SHS）和致敏/暴露于小鼠和蟑螂是肺部炎症潜在来源， SCA的发病率。这项建议的重点是这些常见的接触，可能发生在家庭的儿童， SCA，其中许多人生活在城市，受到贫困的影响。这项提议将扩展萨德里梅利博士以前的路线 一项研究表明，烟草暴露的生物标志物（唾液可替宁）与SCA之间存在很强的相关性， 发病率该项目将把SHS、小鼠和蟑螂暴露的客观测量与临床肺 结果和几种非侵入性措施的嗜酸性和嗜酸性下气道炎症，以提供新的 关于室内环境暴露对SCA肺部发病率和炎症影响的数据。目标1将 评估SHS、肺部结局和嗜肺性炎症之间的相关性。目标2将评估协会 过敏性致敏与暴露于小鼠和蟑螂、肺部结果和嗜酸性粒细胞炎症之间的关系。 通过这项提议，Sadreameli博士将利用她以前的经验和培训，获得以下方面的宝贵专业知识： 环境暴露评估和下气道炎症的非侵入性测量。该研究项目是 可能导致未来的临床试验的环境改造的家庭为基础的干预措施。此外，它将提供 关于SCA下气道疾病炎症机制的有意义的数据。萨德里梅利博士召集了一个 多学科研究团队，具有丰富的研究和指导经验。她的主要导师，莎伦麦格拉思- 莫罗医学博士是一名儿科肺病学家，将提供科学指导，重点是测量 肺部炎症和生理结果以及职业指导。她的共同导师包括詹姆斯F。卡塞拉医学博士， 一名儿科血液学家，将提供与镰状细胞病病理生理学相关的培训和专业知识， 全身炎症结果的生物标志物，Michelle Eakin博士，一位行为心理学家将提供培训 在行为矫正和与健康的社会决定因素的研究相关的专业知识，和克尔斯滕克勒博士， 一位环境健康科学家，他将提供与测量和健康影响有关的指导， 环境暴露。她的研究和职业发展计划以及导师的指导和专业知识将 帮助Sadreameli博士成功实现成为一名成功的独立调查员的长期目标。

Project Summary/Abstract This Mentored Patient-Oriented Research Career Development Award will provide S. Christy Sadreameli, M.D., M.H.S. with experience and training to become an independent investigator in pediatric pulmonology with a focus on the effects of environmental exposures on pulmonary morbidity and inflammation in sickle cell anemia (SCA). Despite advances in the prevention and treatment of SCA, affected children and young adults continue to suffer from a substantial amount of pulmonary morbidity, including episodes of acute chest syndrome (ACS) and respiratory symptoms such as cough and wheezing. Few modifiable risk factors have been identified in SCA, but emerging data suggest that exposure to SHS and other environmental factors are associated with pulmonary morbidity. Indoor environmental exposures such as secondhand smoke (SHS) and sensitization/exposure to mouse and cockroach are potential sources of pulmonary inflammation and morbidity in SCA. This proposal focuses on these common exposures that are likely to occur in the homes of children with SCA, many of whom live in cities and are impacted by poverty. This proposal will extend Dr. Sadreameli’s previous line of research that demonstrated a strong association between a biomarker of tobacco exposure (salivary cotinine) and SCA morbidity. This project will link objective measurement of SHS, mouse, and cockroach exposure with clinical pulmonary outcomes and several non-invasive measures of neutrophilic and eosinophilic lower airway inflammation to provide novel data about the impact indoor environmental exposures have on pulmonary morbidity and inflammation in SCA. Aim 1 will evaluate associations between SHS, pulmonary outcomes, and neutrophilic inflammation. Aim 2 will evaluate associations between allergic sensitization and exposure to mouse and cockroach, pulmonary outcomes, and eosinophilic inflammation. With this proposal, Dr. Sadreameli will build upon her previous experience and training to gain valuable expertise in environmental exposure assessment and non-invasive measurement of lower airway inflammation. This research project is likely to lead to future clinical trials of environmental modification of home-based interventions. Further, it will provide meaningful data about the inflammatory mechanisms of lower airway disease in SCA. Dr. Sadreameli has assembled a multidisciplinary research team with extensive research and mentorship experience. Her primary mentor, Sharon McGrath- Morrow, M.D., is a pediatric pulmonologist who will provide scientific mentorship with focus on measurement of pulmonary inflammatory and physiologic outcomes and career mentorship. Her co-mentors include James F. Casella, M.D., a pediatric hematologist who will provide training and expertise related to sickle cell disease pathophysiology and biomarkers of systemic inflammatory outcomes, Michelle Eakin, Ph.D., a behavioral psychologist who will provide training in behavioral modification and expertise related to the study of social determinants of health, and Kirsten Koehler, Ph.D., an environmental health scientist who will provide mentorship related to the measurement of and health effects from environmental exposures. The research and career development program and the guidance and expertise of her mentors will help Dr. Sadreameli succeed in her long-term goal of becoming a successful independent investigator.