Aerodigestive Disease in the World Trade Center Exposed FDNY Cohort: Validation of Biomarkers and Defining Risk to Tailor Therapy

Details

• Personal Author:
  Nolan A
• Description:
  Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder in the US with estimates as high as 30%, and leads to substantial morbidity. Globally, GERD prevalence is 10-25%, with increased risk in firefighters. PM is a significant component of ambient and occupational exposures that contribute to 7 million deaths annually. Aerodigestive complications include airway hyperreactivity (AHR), Barrett¡¦s Esophagus (BE), and esophageal adenocarcinoma (EAC). However, studies are limited in clarifying the pathophysiological link between obstructive airways disease (OAD), GERD and premalignant BE. Therefore, discovery of biomarkers of GERD/BE, and the overlap of aerodigestive disease is important to identify populations who may benefit from earlier intervention, targeted therapies, attenuate AHR, and improve quality of life. Our work has focused on resolving current gaps of knowledge to validate biomarkers of WTC-aerodigestive disease. Biomarkers of BE may also identify those at risk for neoplastic disease, and may be generalizable to populations with GERD and biomass/PM exposure. Our productive 1st funding period of this U01, included making substantial progress on all original aims and publishing 14 manuscripts. We have presented 18 abstracts at 7 international conferences, authored the chapter "Acute Inhalational Injury" in Irwin and Rippe's Critical Care Textbook (Edition 9). We have started to validate the utility of some of our clinical and serum biomarkers to predict the development of WTC-Aerodigestive disease (AIM 1): Baseline Cohort was further developed and now includes individuals that have an up to date consent for the WTC-HP which includes the use of banked samples (N=4.192). This includes subjects with AHR (N=307); GERD (N=1,412); No GERD or AHR (N=1,348); an Overlap population that had both GERD and AHR (N=1,127) and BE subjects whose GERD led to the development of BE (N=430). Steroid use was associated with increased ORs (95%CI) of developing GERD by 4.65 [3.74- 5.78] p<0.001 and BE by 2.271 [1.806-2.855] p<0.001. Subjects had a 41.0% higher risk of developing BE if they arrived on the morning of 9/11 compared to 31.7% risk if they arrived in the afternoon. In contrast to our pilot assessment SABA use was associated with increased OR of GERD by 4.08[3.50- 4.75] p<0.001 and BE by 1.965 [1.605- 2.406] p<0.001. Subjects with WTC arrival time in the morning of 9/11 had 34.8% higher risk of GERD, compared to 28.8% higher risk in those who arrived in the afternoon of 9/11. Thus far we have studied 322 of our randomly selected representative-cohort of 837. In contrast, to our prior study, Fractalkine an inflammatory chemokine is not predictive of BE or AHR but rather is protective for the development of GERD. IP-10 expression which is induced at high levels in monocytes, neutrophils, and endothelial cells, by stimulation with interferons or lipopolysaccharide remains predictive of the development of BE. C-peptide predicted GERD in our earlier study, opening a new discussion of involvement of insulin in the prediction of the GERD-BE disease cascade. We now find that C-Peptide is still associated with GERD but not BE. Furthermore, C-peptide is protective in regards to the development of AHR. TNF-a is associated with AHR, but in contrast to our prior study it is protective in the development of GERD and is no longer associated with BE. We published/presented preliminary findings relevant to AIM 2: Utilizing the representative-cohort (AIM 1), we are recruiting a subset N=40/group (AHR, GERD, AHR+GERD, BE, and Controls), to quantify noninvasive measures of inflammation (salivary pepsin, serum biomarkers/metabolome, fractional exhaled nitric oxide, exhaled breath condensate (EBC), aerodigestive quality of life/disease severity measures) to phenotype and quantify under-diagnosis/treatment efficacy. We will increase the dimensionality of the WTC Aerodigestive Biorepository by continuing to recruit and accruing non-invasive measures. Thus far in our recruited subjects, salivary pepsin was significantly increased in GERD/BE when compared to either AHR or controls. Similarly, a lower EBC pH was observed in subjects with GERD/BE when compared to controls. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cohort Studies Firefighters Immune System Occupational Health Particulate Matter Respiratory System Safety September 11 Terrorist Attacks
• Keywords:
  Chronic Inflammation Cohort Studies Fire Fighters Gastroesophageal Reflux Disease GERD Immune Reaction Inhalation Particulates World Trade Center WTC
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Final Cooperative Agreement Report
• Place as Subject:
  New York ; New York City Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-14
• NIOSHTIC Number:
  nn:20070818
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, U01-OH-012069, 2024 Dec; :1-14
• Email:
  Anna.Nolan@nyulangone.org
• Federal Fiscal Year:
  2025
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  False
• Start Date:
  20210701
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5dd4f3c5c7e66049a53d8fa7a38246654f591cfc4d81efdb971113741792f5975967c6ec08bb80acf4582ec6c298cb7a623c09d883d9462d8e994e1262253ee0
• Download URL:
  https://stacks.cdc.gov/view/cdc/219284/cdc_219284_DS1.pdf
• File Type:
  [PDF - 1006.45 KB ]