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.

Inclusion Criteria:

1. Age 37-90

2. FDNY rescue and recovery worker.

3. Male*

4. Documented WTC exposure.

5. Consented/Enrolled in the FDNY WTC Health Program

6. Subjects are willing and able to consent for themselves to study enrollment

7. Subjects are willing and able to participate in study procedures

8. Are able to perform their activities of daily living independently

9. Are either light duty or retired FDNY Firefighters

10. Spirometry available within the last 24 months, and at a post-9/11 visit.

11. 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)

12. Pre-9/11 spirometry with FEV1%predicted ≥LLN and if not available 1st -post 9/11 spirometry with an FEV1 >80% predicted.

13. Exposure at the WTC-site within 2 weeks of the 9/11/2001

14. Entered WTC-HP before the site closure on 7/24/2002.

15. Serum from their first post 9/11 WTC-HP visit is available in the FDNY WTC biorepository and may be assayed

16. Are not currently being treated for malignancy

17. 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

18. 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

19. 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:

1. Unwilling to complete an informed consent.
2. Not enrolled in the WTC-HP
3. 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.
4. 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.
5. High dose steroid (>20mg prednisone or equivalent) or other hormonal treatments/chemotherapy use in the last month, including testosterone supplementation.
6. Life-expectancy < 6 months
7. Female*

Less than 1 % of the FDNY-HP subjects are female. As such our prior work has excluded females. In addition, due to this small sample size and since there is significant literature that biomarkers are different in these two sexes, the study team will not be enrolling females.

Male FDNY rescue and recovery workers between the ages of 37 and 90.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose will have access to the data to achieve aims in the approved proposal. Requests should be directed to anna.nolan@med.nyu.edu. To gain access, data requestors will need to sign a data access agreement.