EXposomic Profiling in Airway disease to uNravel Determinants of disease in Asthma (EXPAND-Asthma) Center

气道疾病暴露组分析以解开哮喘疾病的决定因素 (EXPAND-Asthma) 中心

基本信息

批准号：
10744673
负责人：
Stephanie A Christenson
金额：
$ 79.19万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-12 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10744673
关键词：
Acute Adrenergic Agents African American Age Air Pollutants Air Pollution Airway Disease Allergens Allergic Anti-Bacterial Agents Asthma Bacteria Blood Cellular Stress Child Childhood Chronic Disease Clinical Color Communities Complex Custom Data Disease Disease Outcome Emergency department visit Enrollment Environmental Exposure Environmental Risk Factor Event Functional disorder Gene Expression Glucocorticoids Goals Health Heterogeneity Hormones Hospitalization Human Immune Immune response Individual Indoor Air Pollution Inflammation Intervention Latinx Link Mediating Methods Microbe Molecular Monitor Multiomic Data Nitrogen Dioxide Not Hispanic or Latino Outcome Pathologic Pathology Pathway interactions Pharmaceutical Preparations Phenotype Pollution Predisposition Prevalence Psychosocial Stress Recovery Research Infrastructure Resolution Respiratory Tract Infections Risk Factors Role Sampling Signal Transduction Site Social Environment Sputum Stable Disease Stress Techniques Testing Therapeutic Treatment/Psychosocial Effects Viral Virus Vulnerable Populations Work Youth airway immune response airway repair ambient air pollution asthma exacerbation burden of illness clinically relevant cohort community based research data integration fine particles high risk improved indoor pollutant insight low socioeconomic status marginalized community marginalized population metatranscriptomics microbial microbiome multiple omics nasal swab personalized intervention pollutant protein expression psychosocial stressors recruit repaired resilience respiratory response social social factors social stressor socioenvironmental factor stressor study population transcriptomics treatment response

项目摘要

ABSTRACT Asthma is a heterogeneous and highly burdensome disease that is concentrated in communities of color and of low socioeconomic status. Clinical asthma heterogeneity reflects complex interactions between molecular, environmental, and social factors that combine to influence disease outcomes and therapeutic response. Socio- environmental exposures, including psychosocial stressors and air pollution, are concentrated in historically marginalized communities where they contribute to poor asthma outcomes. However, the mechanisms underlying these exposure-related outcomes are poorly understood. There is a critical need to understand how asthma molecular heterogeneity 1) operates in marginalized populations; and, 2) is influenced by prevalent socio-environmental factors. The proposed multi-omics approach considering pathology both systemically and at the main site of disease, the airways, is crucial to unraveling the complex interactions between exposures, mechanisms, and outcomes in these understudied communities. This project aims to enroll 200 youth with and 100 youth without asthma in Richmond, CA, a predominantly Latine community with high socio-environmental stressor burden and asthma prevalence upwards of 25%. Multi-omic data will be derived from blood and airway (nasal swab and sputum) samples collected at disease stability over one year and airway samples collected during acute respiratory events and recovery. These data will be integrated with deep phenotyping and exposure data to test three specific aims. The first aim will examine the relationships between high psychosocial stress and multi-omic outcomes across asthma and health. A hypothesis driven approach will focus on stress- associated asthma-relevant pathologic alterations including systemic and airway immune responses, stress hormone associated microbiome shifts, and beta-adrenergic and glucocorticoid pathology. The second aim will examine the relationships between indoor and outdoor air pollution and multi-omic outcomes across asthma and health. Indoor and fine-resolution outdoor air pollution monitoring will be leveraged for exposure assessments to consider how pollutants relate to immune responses, airway repair, and cellular stress across multi-omic layers. The third aim will examine the role of socio-environmental and microbial precipitants in asthma exacerbation susceptibility and mechanisms, leveraging samples obtained at baseline and during acute respiratory events. A custom multi-omic analytical pipeline that considers microbial exacerbation precipitants along with environmental exposures will be used. Our ultimate goal is to understand the mechanisms underlying socio-environmental exposures that influence asthma outcomes to inform therapeutic and management decisions and influence targets for place-based mitigation efforts.

抽象的哮喘是一种异质和高度繁重的疾病，集中在有色社区和社会经济地位低。临床哮喘异质性反映了分子之间的复杂相互作用环境和社会因素结合起来影响疾病结局和治疗反应。社会环境暴露，包括社会心理压力和空气污染，从历史上集中在历史上边缘化的社区为不良的哮喘结果做出了贡献。但是，机制这些与暴露有关的结果的基础知之甚少。迫切需要了解如何哮喘分子异质性1）在边缘化的人群中运作； 2）受到普遍的影响社会环境因素。拟议中的多词方法都在系统地和在疾病的主要部位，气道对于揭开暴露之间的复杂相互作用至关重要，这些经过研究的社区的机制和结果。该项目旨在注册200名青年和 100名没有哮喘的青年在加利福尼亚州里士满，是一个以高社会环境为主的拉丁社区压力源负担和哮喘患病率超过25％。多摩变数据将来自血液和气道（鼻拭子和痰）在一年内以疾病稳定收集的样品，并收集了气道样品在急性呼吸事件和恢复期间。这些数据将与深度表型和暴露相结合数据测试三个特定目标。第一个目标将研究高社会心理压力之间的关系以及跨越哮喘和健康的多运动结果。假设驱动的方法将集中于压力 - 相关相关的哮喘相关病理改变，包括全身和气道免疫反应，压力激素相关的微生物组移位以及β-肾上腺素能和糖皮质激素病理学。第二个目标检查哮喘和室外空气污染与室外空气污染与多OMIC结局之间的关系健康。室内和精细分辨率室外空气污染监测将被利用以进行暴露评估考虑污染物如何与多摩尼克层之间的免疫反应，气道修复和细胞应激有关。第三个目的将研究社会环境和微生物沉淀剂在哮喘加重中的作用敏感性和机制，利用在基线和急性呼吸事件中获得的样品。一个自定义多摩变分析管道，该管道考虑微生物加重沉淀剂以及环境将使用暴露。我们的最终目标是了解社会环境的基础机制影响哮喘结果的暴露，以告知治疗和管理决策并影响基于场所的缓解工作的目标。