Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)

Official title

AERODIGESTIVE DISEASE IN THE WORLD TRADE CENTER EXPOSED FDNY COHORT: a Single Center Observational Study of Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)

Overview

A majority of Fire Department of New York (FDNY) World Trade Center (WTC) exposed rescue and recovery workers developed gastroesophageal reflux disease (GERD), a risk factor for Barrett's Esophagus (BE) and subsequent esophageal cancer. There is diminished health-related quality of life and productivity associated with aerodigestive diseases such as GERD and BE. This proposal will leverage the longitudinally phenotyped WTC exposed cohort, validate biomarkers of WTC-aerodigestive disease, and develop novel, noninvasive disease phenotyping of premalignant diseases such as BE, and identify potential targeted therapeutics to improve care.

Primary outcome measures

• Levels of salivary pepsin [Time frame: up to Day 365]
• pH Levels from Exhaled Breath Condensate (EBC) [Time frame: up to Day 365]
• Histamine Concentration from Exhaled Breath Condensate (EBC) [Time frame: up to Day 365]
• Score on Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) Questionnaire [Time frame: up to Day 365]
• Score on Patient Assessment of Upper Gastrointestinal Disorders-Symptoms (PAGI-SYM) Questionnaire [Time frame: up to Day 365]
• Score on St. George's Respiratory Questionnaire (SGRQ-C) [Time frame: up to Day 365]
• 36-Item Short Form Survey Instrument (SF-36) [Time frame: up to Day 365]

Eligibility criteria

Inclusion criteria

• Age 37-90
• FDNY rescue and recovery worker.
• Male\*
• Documented WTC exposure.
• Consented/Enrolled in the FDNY WTC Health Program
• Subjects are willing and able to consent for themselves to study enrollment
• Subjects are willing and able to participate in study procedures
• Are able to perform their activities of daily living independently
• Are either light duty or retired FDNY Firefighters
• Spirometry available within the last 24 months, and at a post-9/11 visit.
• Have means to accommodate transportation to/from in-person visit Are able to attend a single visit at the CTSI (462 1st Avenue, C \& D 4th Floor)
• Pre-9/11 spirometry with FEV1%predicted ≥LLN and if not available 1st -post 9/11 spirometry with an FEV1 >80% predicted.
• Exposure at the WTC-site within 2 weeks of the 9/11/2001
• Entered WTC-HP before the site closure on 7/24/2002.
• Serum from their first post 9/11 WTC-HP visit is available in the FDNY WTC biorepository and may be assayed
• Are not currently being treated for malignancy
• Subjects will either need to be defined as having WTC-AHR, WTC-GERD, WTC-BE or be designated controls as per the following additional inclusion criteria are specific to the WTC-aerodigestive disease that the subjects have
• AHR--A positive methacholine (PC20<16) and/or positive bronchodilator response (ATS/ERS guidelines: improvement of FEV1 by 12% and at least 200mL) at least once post-9/11.\[95, 96\]No recorded positive AHR testing prior to 9/11
• GERD Inclusion Criteria

• Erosive esophagitis LA grade C or D (as described on endoscopy), OR
• Stricture or Barrett's esophagus on endoscopy, OR
• Esophageal acid exposure time >6% on a pH or pH impedance study

19\. BE Inclusion Criteria

• Columnar epithelium lining ≥1 cm of the distal esophagus. AND
• Histologic examination of biopsy specimens from that columnar epithelium must reveal intestinal metaplasia characterized with goblet cells.

Exclusion criteria

• Unwilling to complete an informed consent.
• Not enrolled in the WTC-HP
• Do not meet eligibility criteria for AIM 1 or did not have serum available in the biorepository from the first post 9/11 WTC-HP visit.
• Have pre-existing and documented conditions or concurrent diagnoses, including (and not necessarily limited to) active cancer, severe heart disease, significant cognitive impairment, eating disorders, significant psychiatric illness, end-stage COPD, severe pulmonary hypertension, or organ transplant.
• High dose steroid (>20mg prednisone or equivalent) or other hormonal treatments/chemotherapy use in the last month, including testosterone supplementation.
• Life-expectancy < 6 months
• Female\*

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• NYU Clinical & Translational Science Institute Clinical Research Center (CTSI CRC) — New York

Publications

• Javed U, Podury S, Kwon S, Liu M, Kim DH, Fallahzadeh A, Li Y, Khan AR, Francois F, Schwartz T, Zeig-Owens R, Grunig G, Veerappan A, Zhou J, Crowley G, Prezant DJ, Nolan A. Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN) in World Trade Center exposed firefighters: a case-control observational study protocol. BMC Gastroenterol. 2024 Aug 9;24(1):255. doi: 1 PMID 39123126
• Javed U, Podury S, Kwon S, Liu M, Kim D, Fallah Zadeh A, Li Y, Khan A, Francois F, Schwartz T, Zeig-Owens R, Grunig G, Veerappan A, Zhou J, Crowley G, Prezant D, Nolan A. Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN): a Case-Control Observational Study Protocol. Res Sq [Preprint]. 2024 May 15:rs.3.rs-4355584. doi: 10.21203/rs.3.rs-4355584/v1. PMID 38798396

Identifiers

NCT: NCT05216133 · 21-00679

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗