Metabolic Profile Linked to Respiratory Disease Risk in September 11 Responders

Anna Nolan, MD

A study has identified several key metabolic pathways that predicted the development of obstructive airways disease (OAD) in firefighters and first responders involved in the aftermath of the attack on the World Trade Centers on September 11.

During the aftermath of disaster 17 years ago today, workers were exposed to particulate matter that consisted of various metals including mercury and iron, and construction materials such as powdered concrete and silicates.

As a consequence, many of those workers developed what is termed World Trade Center Lung Injury (WTC-LI), a collection of chronic respiratory conditions, such as asthma and emphysema.

Senior study investigator, Anna Nolan, MD, associate professor in the Department of Medicine at New York University, said that she and another research team found that metabolic syndrome biomarkers have association with loss of lung function in a study published in 2012.

“For this [current] study, we wanted to look at the 700 or so metabolites that we can quantify in order to better understand what’s going on with the cells involved here,” Nolan said.

Metabolic syndrome is a group of inter-related risk factors that increase the chances of developing heart disease, diabetes, and stroke. Those risk factors include elevated blood sugar, central obesity (excess fat around the stomach), increased blood pressure, high triglyceride levels and low HDL (good cholesterol).

Blood serum samples were taken from 30 firefighters on-site in the September 11 attack aftermath. The participants were non-smokers, all male, exposed to similar levels of WTC dust. Their lung function was tested within 7 months of the disaster and continued to be tested annually. They were divided into 2 groups: firefighters whose lung function had declined severely by 2015 (n = 15) and firefighters whose lung function remained healthy (15).

Results determined a refined metabolite profile consisting of 5 clusters of metabolites that accurately predicted lung injury and disease for most subjects. One of the most prominent pathways included the sphingolipid cluster, which contain sphingosine 1-phosphate, an inflammation mediator and plays a role in asthma triggers.

Another pathway of note is the branched-chained amino acids (BCAA), particularly several leucine, isoleucine, and valine metabolites. Low levels of BCAAs have been found in the blood of patients with chronic obstructive pulmonary disease (COPD) and dietary supplementation of BCAAs has been shown to alleviate respiratory muscle weakness related to COPD.

The possibility of being able to improve or restore lung function with dietary changes or supplementation is an innovative development.

“These findings have been previously identified in other OAD populations,” Nolan said. “But because there seems to be a significant genetic component potentially involved here, these findings should be validated in larger populations that includes confounders, like a smoking population, and other ethnic groups.”

In addition to validating results in a larger population, next steps will also include a randomized clinical trial focused on diet modification in an attempt to alter the factors that were associated with poor lung function.

The study, “Metabolomics of World Trade Center-Lung Injury: a machine learning approach” was published online in the journal BMJ Open Respiratory Research.