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

基本信息

批准号：
10678701
负责人：
Anna Nolan
金额：
$ 59.97万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/10678701
关键词：
Metabolomics World Trade Center Lung

项目摘要

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.

概括世界贸易中心不久后表达的代谢综合征生物标志物（METSYN）和血管疾病（WTC）颗粒物（PM）暴露预测WTC肺损伤（WTC-LI）的发展。但是，鉴定WTC-PM相关疾病的生物签名和分子决定因素尚未全面表征并保持未开发的资源。而遗传和环境因素是许多疾病过程的基础，代谢组分析提供了与疾病表型的紧密联系并受到微生物组的深刻影响。组合的多构方法具有成为WTC-LI早期诊断的有效工具疾病预后，治疗反应的监测标志物以及进一步疾病发展的检测。此外，通过技术支持的多学科营养减少METSYN风险因素干预还可以改善BMI，肺功能和生活质量度量。我们假设WTC-LI的多层生物签名将有助于理解动态生物学环境影响改变的途径导致对PM暴露的异源反应和治疗。我们将调查： 1。多组学，包括现象学，代谢物，微生物组和与WTC-LI相关的基因组谱在我们的试点症状消防室RCT队列中。然后，我们将使用系统生物学整合多组优化特定疾病模型并确定WTC-LI的相关途径。 2。使用纵向表型和身体，心肺和心理健康的多学科评估。反馈将使用焦点小组和问卷。 3。可行性和需求评估。这将是首次在WTC暴露受试者中的多构研究，能够识别WTC-LI个体中的独特模式，并激发特定的治疗性方法。这将使我们能够最终实施消防屋模型。我们将使用共同的决策进行可行性，并需要评估。我们的验证其他人群中的营养结果将证明其普遍性并有助于其他WTC暴露的人群。四年结束时的总体目标是了解我们量身定制的营养的长期影响干涉。该赠款产生的数据将提高对WTC-LI的理解，并增强我们的能力诊断和治疗与WTC相关的气道损伤。合格的生物签名可以在其他方面进行外部验证可能会从技术中受益的BMI和大型PM暴露的同类人群支持的饮食修饰。可以在面对的其他同类团队中验证从这项调查中学到的经验教训由于大量的PM暴露而引起的大量公共卫生问题，谁可能会从有针对性的疗法中受益。