SUMMARY The destruction of the World Trade Center (WTC) led to the exposure of thousands of first responders and inhabitants of New York City to WTC-particulate matter (WTC-PM). WTC-PM exposure in our Fire Department of New York (FDNY) cohort is associated with the development of obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE). GERD is a well-known risk factor of the metaplastic changes of BE, which can subsequently lead to adenocarcinoma. GERD is also associated with occupational or environmental exposure related OAD. Overall, WTC-exposed firefighters with OAD had a three times higher risk of developing GERD. At least 40% of WTC rescue and recovery workers have developed GERD symptoms, which is 8.2 times its pre-9/11 prevalence. It is in the context of these findings that we propose to study, Aerodigestive Disease in the World Trade Center Exposed FDNY Cohort: Validation of Biomarkers and Defining Risk to Tailor Therapy. This will further define and phenotype aerodigestive/gastrointestinal health biomarkers, as well as determine impact on lung health to improve care thereby fulfilling the mandate of the James Zadroga 9/11 Health & Compensation Act: PAR-20-280. GERD diminishes health-related quality of life and productivity. Complications of GERD can further extend beyond BE; extra-esophageal reflux can incite or exacerbate allergies, sinusitis, chronic bronchitis, and asthma. Management of reflux is challenging, as often refractory to therapy, diagnosis can be invasive and have significant associated costs. Patients with WTC-PM exposure associated asthma more often had persistent GERD. Furthermore, GERD increases the odds of developing WTC-AHR, independent of exposure intensity. Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. We have successfully identified metabolic, vascular and inflammatory biomarkers of WTC-airway hyperreactivity (WTC-AHR). We have also identified biomarkers of GERD/BE in our WTC exposed population with respiratory disease, facilitating the identification of biologically relevant immune pathways. We propose two AIMs to explore the HYPOTHESIS that serum biomarkers will differentiate FDNY rescue and recovery workers with aerodigestive morbidity who proceed to develop GERD/BE. Noninvasive biomarkers will identify subjects that may require improved treatment. We are requesting funding of our translational research to leverage the longitudinally phenotyped FDNY-WTC cohort and identify Biomarkers of Airway Disease, Barrett’s and Underdiagnosed Reflux Noninvasively (BAD-BURN). We will develop the WTC aerodigestive repository, validate biomarkers of GERD and BE (AIM 1), and phenotype subgroups with aerodigestive disease to identify noninvasive biomarkers of diagnosis/treatment efficacy to inform future biologically plausible therapies to improve care (AIM 2).