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Rescue workers exposed to World Trade Center particulate matter on September 11, 2001 (9/11), had a wide range of lung function outcomes. As part of the , a longitudinal study of nearly 13,000 first responders at the 9/11 disaster site, ��ɫtv Langone Health researchers have identified specific physiologic factors that may account for these differences—factors that predict World Trade Center lung injury (WTC-LI) and, separately, factors that are associated with resistance to lung injury.

Metabolic Syndrome as a Predictive Factor

Researchers found that the most significant single predictive factor of post-9/11 lung disease in first responders is metabolic syndrome (MetSyn)—diagnosed by the presence of three or more of following: abdominal obesity, insulin resistance, hypertriglyceridemia, low levels of high-density lipoprotein (HDL), and hypertension. In fact, MetSyn exerts a greater effect on the risk for WTC-LI (increased risk of 55.7 percent) than having the highest level of exposure to particulate matter (30.1 percent) or history of cigarette smoking (15.2 percent). What’s more, the study found a MetSyn dose–response effect. Presence of just one of the five MetSyn criteria increased risk by 30.2 percent; two increased risk by 30.5 percent.

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“Our study confirms that metabolic syndrome has as much of an impact on the lungs as it does on the heart,” says study senior investigator Anna Nolan, MD, associate professor in the at ��ɫtv Langone. “It’s a vital step in the investigation of MetSyn as a potentially modifiable risk factor for lung disease associated with particulate matter.”

Individual Metabolome Can Predict Protection Against Post-9/11 Lung Injury

In a separate investigation, , ��ɫtv Langone researchers assessed the metabolome (the ecosystem of low-molecular-weight metabolites) of a small subset of 9/11 firefighters who demonstrated resistance to lung injury. Of 594 qualified metabolites looked at, researchers identified 30 that were present in greater amounts in subjects who did not develop obstructive airway disease (OAD) compared with controls. Those more likely to be resistant had elevated amino acid and long-chain fatty acid metabolites, as well as reduced hexose monophosphate shunt metabolites.

This study is the first to suggest the specific compounds associated with resistance to subsequent loss of lung function in emergency workers who arrived at the World Trade Center disaster site before September 13, 2001.

“The metabolic pathways that characterize those who were resistant to lung disease could inform the development of potential therapeutic targets,” says Dr. Nolan.

Applying These Findings Beyond 9/11 Responders

Although the exposure of 9/11 emergency workers to the particulate matter of that disaster may be unique, the study findings may apply to individuals exposed to toxic particulate matter from wildfires and urban air pollution. Researchers are hopeful that drugs, dietary changes, and regular exercise can be protective.

Disclosures: Anna Nolan, MD, received funding for the Scientific Reports study from National Institutes of Health grants R01HL119326, UL1TR000038, 200-2017-93426, 200-2017-93326; National Institute for Occupational Safety and Health/Centers for Disease Control and Prevention grant U01OH11300; and the Saperstein Scholars Fund.