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

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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.