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

• 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
• 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

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.

摘要 哮喘是一种异质性和高度负担的疾病，集中在有色人种和少数民族社区。 社会经济地位低下。临床哮喘异质性反映了分子， 联合收割机影响疾病结果和治疗反应的环境和社会因素。社会的，社会的 环境暴露，包括心理社会压力和空气污染，历史上集中在 边缘化的社区，他们有助于哮喘的不良结果。然而，机制 对这些与自杀相关的结果的基本原因知之甚少。我们迫切需要了解 哮喘分子异质性1）在边缘人群中起作用; 2）受流行性哮喘的影响， 社会环境因素。所提出的多组学方法从系统和 在疾病的主要部位，呼吸道，对于解开暴露之间的复杂相互作用至关重要， 机制和结果。该项目旨在招收200名青年， 在加利福尼亚州里士满（一个主要为拉丁裔的社区，具有较高的社会环境风险）的100名无哮喘的青年 压力源负担和哮喘患病率高达25%。多组学数据将来自血液和气道 （鼻拭子和痰液）在疾病稳定超过一年时采集的样本和采集的气道样本 在急性呼吸道事件和恢复期间。这些数据将与深度表型分析和暴露相结合 测试三个具体目标。第一个目标是研究高心理社会压力与 以及哮喘和健康的多组学结果。假设驱动的方法将侧重于压力- 相关的哮喘相关的病理改变，包括全身和气道免疫反应，应激 激素相关的微生物组变化以及β-肾上腺素能和糖皮质激素病理学。第二个目标将 检查室内和室外空气污染与哮喘多组学结果之间的关系， 健康将利用室内和高分辨率室外空气污染监测进行暴露评估， 考虑污染物如何与免疫反应、气道修复和跨多组学层的细胞应激相关。 第三个目标是研究社会环境和微生物沉淀物在哮喘急性发作中的作用 敏感性和机制，利用基线和急性呼吸事件期间获得的样本。一 自定义多组学分析管道，其考虑微生物恶化沉淀物沿着环境 曝光将被使用。我们的最终目标是了解社会环境的潜在机制 影响哮喘结果的暴露，以告知治疗和管理决策， 以地点为基础的缓解努力的目标。