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.

项目摘要 这项提案的目的是了解镰状细胞免疫反应如何影响儿童的免疫功能。 细胞疾病（cwSCD）是由暴露在当地环境中形成的，并导致不同的 健康成果。这一建议的基本原理是，我们先前的工作表明， cwSCD在其血液炎症转录谱中具有独特的改变， 基线时的气道微生物组，在急性并发症期间进一步扰动。我们有 还表明，公共卫生问题组（PHE），其中包括来自自然， 建筑，社会和政策环境，影响慢性疾病的炎症。的 拟议的研究是重要的，因为SCD预防性地影响代表性不足 少数民族人口中的许多儿童经常受到多种因素的影响和挑战， 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炎症反应的频率增加， 并发症中心假设将通过追求两个具体目标进行测试：1） 表征SCD基线免疫特征和2）将环境和社会- 从PHE 4.0数据库中的人口统计学因素到个人，社区， 和人口水平。我们将使用复杂的转录和 结合实时PHE数据的新型数据库的免疫特征蛋白质组学分析 和充分表征的临床数据。我们的跨学科免疫学专家团队， 微生物学和公共卫生沿着血液学、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。这项工作的预期成果将建立一个独特的概况， 免疫特征与PHE集成，生成无与伦比的生物数据集 数据与社会和环境因素，影响健康的cwSCD。长期 目的是将研究结果与气道和肠道的综合评估相结合 微生物组和激素应激反应，并纵向评估如何 免疫环境因素预测急性并发症。最终，我们将创造 全面的cwSCD表型特征，以帮助改善预测，预防， cwSCD急性并发症的治疗，超越了目前的范式， 支持性和/或反应性护理。