Faculty Bibliography

The metabolome of World Trade Center (WTC) particulate matter (PM) exposure has yet to be fully defined and may yield information that will further define bioactive pathways relevant to lung injury. A subset of Fire Department of New York firefighters demonstrated resistance to subsequent loss of lung function. We intend to characterize the metabolome of never smoking WTC-exposed firefighters, stratified by resistance to WTC-Lung Injury (WTC-LI) to determine metabolite pathways significant in subjects resistant to the loss of lung function. The global serum metabolome was determined in those resistant to WTC-LI and controls (n = 15 in each). Metabolites most important to class separation (top 5% by Random Forest (RF) of 594 qualified metabolites) included elevated amino acid and long-chain fatty acid metabolites, and reduced hexose monophosphate shunt metabolites in the resistant cohort. RF using the refined metabolic profile was able to classify cases and controls with an estimated success rate of 93.3%, and performed similarly upon cross-validation. Agglomerative hierarchical clustering identified potential influential pathways of resistance to the development of WTC-LI. These pathways represent potential therapeutic targets and warrant further research.

Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001-24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor.