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

项目摘要/摘要 这项以患者为导向的导师研究职业发展奖将为S.Christy Sadreameli，M.D.，M.H.S. 拥有经验和培训，将成为儿科肺病学的独立研究员，专注于 环境暴露对镰状细胞性贫血(SCA)肺部发病率和炎症的影响。尽管在这方面取得了进展 预防和治疗SCA，受影响的儿童和年轻人继续遭受大量 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 气喘吁吁。在SCA中几乎没有发现可修改的危险因素，但新出现的数据表明，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，如二手货 烟雾(SHS)和对老鼠和蟑螂的致敏/暴露是肺部炎症和 SCA的发病率。这项提案关注的是这些可能发生在儿童家中的常见接触。 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雷梅利博士之前的路线 表明烟草暴露的生物标志物(唾液可替宁)与SCA之间存在强烈关联的研究 发病率。该项目将把SHS、老鼠和蟑螂暴露的客观测量与临床肺部疾病联系起来 中性粒细胞和嗜酸性下呼吸道炎症的结果和几种非侵入性措施提供新的 关于室内环境暴露对SCA肺部发病率和炎症的影响的数据。目标1将 评估SHS、肺转归和中性粒细胞炎症之间的关系。目标2将评估协会 过敏反应和暴露于老鼠和蟑螂、肺部结局和嗜酸性炎症之间的关系。 有了这项建议，萨德雷亚梅利博士将以她以前的经验和培训为基础，获得宝贵的专业知识 下呼吸道炎症的环境暴露评估和非侵入性测量。这项研究项目是 可能导致未来对家庭干预措施进行环境改造的临床试验。此外，它将提供 关于SCA下呼吸道疾病炎症机制的有意义的数据。Sadreameli博士已经组装了一个 具有广泛研究和指导经验的多学科研究团队。她的主要导师莎伦·麦格拉思- Morrow医学博士是一位儿科肺科医生，他将提供科学指导，重点是测量 肺部炎症和生理结果与职业指导。她的联合导师包括詹姆斯·F·卡塞拉，医学博士， 一名儿科血液学家，将提供有关镰状细胞病病理生理学和 全身性炎症结果的生物标记物，米歇尔·埃金博士，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研究相关的专业知识方面，以及Kirsten Koehler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 暴露在环境中。研究和职业发展计划以及她导师的指导和专业知识将 帮助Sadreameli博士成功实现她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.