SMILE: Sickle Cell Disease Microbiologic and Immunologic Links to Health Equity

SMILE：镰状细胞病微生物学和免疫学与健康公平的联系

• 批准号: 10574746
• 负责人: Susan Creary
• 金额: $ 22.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574746
• 关键词: Acute; Address; Age; Air; Anti-Inflammatory Agents; Big Data Methods; Biological; Blood; Caring; Cell Culture Techniques; Characteristics; Child; Child Health; Chronic; Chronic Disease; Clinical; Clinical Data; Cohort Analysis; Communities; Data; Data Set; Databases; Development; Disease Outcome; Disparate; Environment; Environmental Exposure; Environmental Risk Factor; Erythrocytes; Event; Exogenous Factors; Exposure to; Foundations; Frequencies; Future; Gene Expression Profile; Genetic; Genetic Transcription; Goals; Health; Hematological Disease; Hematology; Hormonal; Human; Immune; Immune response; Immune system; Immunologics; Immunology; Individual; Inflammation; Inflammatory; Knowledge; Lead; Link; Liquid substance; Longitudinal cohort; Lung; Microbe; Microbiology; Minority Groups; Mission; Modeling; Morbidity - disease rate; Nasal Epithelium; Outcome; Outcome Study; Pain; Participant; Pathway interactions; Phenotype; Policies; Population; Predictive Factor; Prevention; Proteomics; Public Health; Pulmonology; Race; Recurrence; Research; Risk; Sampling; Shapes; Sickle Cell; Sickle Cell Anemia; Signal Transduction; Societal Factors; Soil; Specialist; Technology; Testing; Therapeutic Intervention; Time; Underrepresented Minority; United States National Institutes of Health; Variant; Water; Work; acute chest syndrome; biological adaptation to stress; built environment; cohort; design; disorder control; effective intervention; experience; gut microbiome; health disparity; health equity; health outcome disparity; high risk; immune function; improved; innovation; mortality; novel; novel strategies; preventive intervention; prospective; respiratory microbiome; social; social health determinants; sociodemographic factors; stressor; transcriptomics; vaso-occlusive pain

PROJECT SUMMARY The objective of this proposal is to understand how immune responses in children with sickle cell disease (cwSCD) are shaped by exposures in their local environment and lead to disparate health outcomes. The rationale underlying this proposal is that our prior work demonstrates that cwSCD have unique alterations in their blood inflammatory transcriptional profiles and upper airway microbiomes at baseline with further perturbations during acute complications. We have also shown that the public health exposome (PHE), which includes stressors from the natural, built, social, and policy environments, influences inflammation in chronic diseases. The proposed research is significant because SCD disproportionally impacts underrepresented minority populations with many children frequently exposed to and challenged by multiple negative social determinates of health. The central hypothesis is that the PHE is associated with altered inflammatory signaling in cwSCD leading to increased frequency of acute complications. The central hypothesis will be tested by pursuing two specific aims: 1) Characterize SCD baseline immune signatures and 2) Link environmental and socio- demographic factors from the PHE 4.0 database to SCD outcomes at the individual, community, and population-levels. We will pursue these aims using sophisticated transcriptional and proteomic profiling of immune signatures combined with a novel database of real-time PHE data and well-characterized clinical data. Our interdisciplinary team of experts in immunology, microbiology, and public health along with hematology, pulmonology, and ID specialists combines complementary clinical and research expertise to take a new approach to study outcomes in cwSCD. The expected outcome of this work will establish a unique profile of immune signatures integrated with the PHE to generate an unparalleled dataset of biologic data with societal and environmental factors that influence health in cwSCD. The long-term goal is to integrate findings with a comprehensive assessment of the airway and gut microbiomes and hormonal stress responses from this cohort and longitudinally evaluate how immune-environmental factors predict acute complications. Ultimately, we will create comprehensive phenotypic profiles of cwSCD to help improve prediction, prevention, and treatment of acute complications in cwSCD that move beyond the current paradigm of supportive and/or reactive care.

项目总结 这项建议的目的是了解患有镰刀的儿童的免疫反应 细胞疾病(CwSCD)是由暴露在当地环境中形成的，并导致不同的 健康结果。这一提议背后的理由是，我们之前的工作表明 慢性硬膜下血友病患者的血液炎性转录水平和上 在急性并发症期间有进一步扰动的基线的呼吸道微生物群。我们有 还表明，公共卫生暴露(PHE)，包括来自自然的压力源， 固有的、社会的和政策的环境影响慢性疾病的炎症。这个 拟议的研究意义重大，因为SCD对代表性不足的影响不成比例 有多个孩子的少数族裔人口经常接触和挑战 健康的负面社会决定因素。中心假设是Phe与 CwSCD中炎症信号的改变导致急性 并发症。核心假设将通过追求两个具体目标来检验：1) 表征SCD基线免疫特征和2)将环境和社会- 人口因素，从Phe 4.0数据库到个人、社区、 和人口水平。我们将使用复杂的转录和 免疫特征的蛋白质组学分析与一个新的实时Phe数据数据库相结合 和具有良好特征的临床数据。我们跨学科的免疫学专家团队， 微生物学和公共卫生，以及血液学、肺病学和ID专家 结合互补的临床和研究专业知识，采取新的研究方法 Cwscd的结果。这项工作的预期结果将建立一个独特的概况 与Phe集成的免疫特征生成无与伦比的生物数据集 Cwscd中影响健康的社会和环境因素的数据。长期的 目标是将发现与对呼吸道和肠道的全面评估相结合 来自该队列的微生物群和激素应激反应以及纵向评估如何 免疫环境因素可预测急性并发症。最终，我们将创造 CwSCD的全面表型特征有助于改进预测、预防和 慢性阻塞性肺疾病急性并发症的治疗超越了目前的 支持性和/或反应性护理。