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Metabolite Analysis Predicts 9/11 Lung Damage

Analysis of blood samples taken from World Trade Center (WTC) firefighters soon after 9/11 led to the identification of more than two dozen metabolites that, in a retrospective analysis, reliably predicted which workers would go on to develop lung disease.

The metabolomic study identified “plausible pathways associated with loss of lung function” that could potentially lead to metabolic tests for the early detection of lung damage associated with exposure to fire, smoke, and toxic chemicals, New York University Langone School of Medicine researchers reported in BMJ Open Respiratory Research.

The findings also raise the intriguing possibility that dietary changes aimed at reducing triglycerides and raising high-density lipoprotein cholesterol could prevent declines in lung function following injury due to smoke or toxic chemical exposure, Anna Nolan, MD, of the Department of Environmental Medicine, told MedPage Today.

She said the investigators plan to test the theory in the first dietary study involving WTC-exposed firefighters by comparing lung outcomes among those on standard diets with those who eat a mostly plant, olive oil, and fish-based Mediterranean diet.

In the newly reported study, the researchers analyzed blood levels of 580 metabolites from never-smoking, male WTC-exposed firefighters with documented normal pre-9/11 lung function from blood samples taken within 200 days of the disaster. Lung function testing was performed annually following the participants’ work at Ground Zero.

Using advanced computer software incorporating machine learning techniques, the researchers analyzed the metabolic data from firefighters whose lung functions sharply declined after 9/11 and those whose lung functions remained normal.

When the investigators plotted all the metabolites on graphs, they were able to identify groups of chemical signatures that were highly predictive of obstructive airway disease and lung injury. Metabolite profiles highly predictive of obstructive airway disease and lung injury included the following:

  • Decreases in sphingolipids, such as sphingosine 1-phosphate, which is a fat that has previously been linked with asthma and inflammation
  • Declines in branch-chain amino acids, including leucine and valine, which have been linked with chronic obstructive pulmonary disease in some studies
  • Increases in levels of stress hormones, including vanillylmandelate, which may lead to elevated levels of fatty acids leading to inflammation

Using the computer analysis, the researchers correctly classified subjects with a 93.3% estimated success rate. Principal component analysis of the refined profile explained 68.3% of variance in five identified components, demonstrating class separation.

“Although the metabolome reflects the complex interaction between many different parent cells, our data suggest that the most biologically active WTC-lung injury-associated metabolites reflect lipids and amino acids.

“Several of these have been identified as associated with broader categories of obstructive lung injury, and, in line with our hypothesis, these metabolites clustered in patterns representative of their established mechanisms; however, other clusters contain novel metabolites. Overall, these metabolite clusters represent biologically plausible signalling cascades.”

In addition, Nolan and co-authors noted, dietary fatty acids may be able to alter the lipidomic signature that characterized the WTC-lung injury subjects: “Specifically, a diet that is low in saturated fat intake and has a low omega-6-to-omega-3 fatty acid ratio may help correct high ceramide and the imbalance in phospholipid-derived long-chain PUFA metabolites, which could have downstream beneficial effects on inflammatory and insulin signalling pathways.”

Regarding the future study, Nolan told MedPage Today that the plan is to recruit approximately 140 WTC firefighters for the dietary investigation, which will be funded by the National Institute for Occupational Safety and Health. Participants will be asked to follow a standard diet or a Mediterranean diet high in olive oil, vegetables, and grains and low in red meat for 6 months to determine if those following the Mediterranean diet show improvements in lung function or body mass index.

Funding for the research was provided by the National Institute of Health‘s National Center for Advancing Translational Sciences and the Saperstein Scholars Fund.

Nolan and co-authors reported having no relevant relationships with industry related to the research.

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