Metabolomics of World Trade Center-Lung Injury: Biomarker Validation, Longitudinal Assessment and Dietary Intervention

世贸中心肺损伤的代谢组学：生物标志物验证、纵向评估和饮食干预

• 批准号: 10535944
• 负责人: Anna Nolan
• 金额: $ 59.99万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10535944
• 关键词: Metabolomics; World; Trade; Center; Lung

SUMMARY Biomarkers of metabolic syndrome(MetSyn) and vascular disease expressed soon after World Trade Center (WTC) particulate matter (PM) exposure predict development of WTC-Lung Injury (WTC-LI). However, the identification of biosignatures and molecular determinants of WTC-PM related disease are yet to be comprehensively characterized and remain as untapped resources. Whereas genetic and environmental factors are the foundation of many disease processes, metabolomic profiling provides a close link to disease phenotype and is profoundly influenced by the microbiome. A combined multiOMIC approach has the potential to be an effective tool for early diagnosis of WTC-LI, predictor of disease prognosis, surveillance marker of treatment response, and detection of further disease development. Furthermore, reducing MetSyn risk factors through a technology-supported multidisciplinary nutritional intervention can also improve BMI, lung function and quality of life measures. We hypothesize that multiOMIC biosignatures of WTC-LI will facilitate the understanding of the dynamic biologic pathways that are altered by environmental influences that lead to a heterogenous response to PM exposure and treatment. We will investigate the: 1. MULTIOMICS, including phenomics, metabolites, microbiome and genomic profiles associated with WTC-LI in our pilot symptomatic FIREHOUSE RCT cohort. We will then integrate the MultiOME using systems biology to optimize disease specific models and identify pertinent pathways of WTC-LI. 2. LONG-TERM EFFECTIVENESS of the FIREHOUSE treatment model using longitudinal phenotypic and multidisciplinary assessment of physical, cardiopulmonary, and mental health. Feedback will be obtained using focus groups and questionnaires. 3. FEASIBILITY AND NEED ASSESSMENT. This will be the first multiOMIC study in WTC-exposed subjects, enabling the identification of distinctive patterns in individuals with WTC-LI, and motivating specific therapeutic approaches. This will allow us to lay the ground work for the eventual implementation of the FIREHOUSE model. We will undertake a feasibility and need assessment using shared decision-making. VALIDATION of our nutritional findings in additional cohorts will prove its generalizability and assist other WTC exposed populations. The overall goal at the end of four years will be to understand the long-term effects of our tailored nutritional intervention. Data generated by this grant will improve the understanding of WTC-LI and enhance our ability to diagnose and treat WTC-related airway injury. Qualified bio-signatures can be externally validated in other cohorts that face significant elevations of BMI and heavy PM exposure who may also benefit from the technology- supported diet modification. Lessons learned from this investigation can be validated in other cohorts who face significant public health concerns due to heavy PM exposure, and who may benefit from targeted therapies.

摘要 代谢综合征(MetSyn)和血管疾病的生物标志物在世贸中心后不久表达 (WTC)颗粒物(PM)暴露可预测WTC-肺损伤(WTC-LI)的发生。然而， WTC-PM相关疾病的生物学特征和分子决定因素的鉴定尚未完成 全面表征，并仍是未开发的资源。鉴于遗传和环境因素 是许多疾病过程的基础，代谢组谱与疾病表型密切相关 并且深受微生物群的影响。 多OMIC联合检测有可能成为WTC-LI早期诊断的有效工具 疾病预后、治疗反应的监测标记物和疾病进一步发展的检测。 此外，通过技术支持的多学科营养降低MetSyn风险因素 干预还可以改善BMI、肺功能和生活质量指标。 我们推测WTC-LI的多OMIC生物签名将有助于理解动态的生物 被环境影响改变的途径，导致对PM暴露的异质性反应 和治疗。我们将调查： 1.多生物学，包括与WTC-LI相关的表型组学、代谢产物、微生物组和基因组图谱 在我们的飞行员症状消防站RCT队列中。然后我们将使用系统生物学来整合多OME 优化疾病特异性模型，寻找WTC-LI的相关途径。 2.消防站治疗模式的长期有效性使用纵向表型和 身体、心肺和精神健康的多学科评估。反馈将通过以下方式获得 焦点小组和问卷调查。 3.可行性和必要性评估。这将是第一次在WTC暴露的受试者中进行多OMIC研究， 能够识别患有WTC-LI的个体的独特模式，并激发特定的治疗 接近了。这将使我们能够为最终实施消防站模式奠定基础。 我们将利用共享决策进行可行性和需求评估。验证我们的 在其他队列中的营养发现将证明其普适性，并有助于其他WTC暴露人群。 四年后的总体目标将是了解我们量身定做的营养的长期影响 干预。这笔赠款产生的数据将增进对WTC-LI的了解，并增强我们的能力 诊断和治疗WTC相关的呼吸道损伤。合格的生物签名可以在其他 面临BMI显著上升和大量PM暴露的队列，他们也可能从这项技术中受益- 支持饮食修改。从这次调查中吸取的教训可以在其他面临 由于大量PM暴露而引起的重大公共卫生问题，以及谁可能受益于靶向治疗。