— Sphingolipids in breath condensate had high predictive accuracy in distinguishing two conditions
October 20, 2026 • 3 min read
PHOENIX -- Exhaled sphingolipids appeared to distinguish between idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis, potentially offering a path toward noninvasive testing, researchers reported here.
The presence of sphingomyelin C24:0 in exhaled breath condensate correctly predicted fibrotic hypersensitivity pneumonitis in 80% of cases and IPF in 85.7%, for an area under the receiver operating curve of 0.897.
A blood test for plasma dihydrosphingosine had modest predictive accuracy on its own, with an area under the receiver operating curve of 0.737, and didn't add much to the performance of the breath test (combined AUC 0.906), Jon Mullholand, MD, of Virginia Commonwealth University in Richmond, reported at the CHESTopens in a new tab or window meeting hosted by the American College of Chest Physicians.
"There's a diagnostic challenge when we're trying to differentiate these [two conditions] at end-stage disease, as they can have overlapping clinical presentations as well as imaging features, even pathologic slides," he said. "And it's important to distinguish these because they have differences in management as well as prognosis."
Getting the wrong treatment in either direction ultimately impacts outcomes and potentially mortality, Mullholand noted.
The results showed that the sphingolipid species in exhaled breath condensate alone "is the strongest predictor that we have to date with noninvasive sampling whatsoever," he said.
These tests are not available as a common assay in the case of plasma sphingolipids nor accepted for analysis by many labs across the U.S. in the case of exhaled breath condensate, Mullholand noted.
"Ultimately the testing is actually cheap, noninvasive, and easy to collect," he told MedPage Today. "So if we can verify [the results in an external validation study], ultimately I think this could be quickly applied to clinical practice."
Exhaled breath condensate is collected in a tube akin to an inhaler. A refrigerant inside condenses the patient's breath into a sample that can be pulled out for testing. However, research into exhaled breath condensate dropped off around a decade ago, in part for practical reasons, Mullholand said: "It's kind of a volatile assay, and of itself it's difficult for people to do. ... It takes anywhere from 15 to 20 minutes. And then if you ask somebody with bad lungs to do that, it's tough."
Sphingolipids play a role in inflammation and fibrosis, and prior studies have identified altered sphingolipids in IPF.
Breath condensate gives a window into the "actual local environment" in the lungs, rather than the more systemic picture painted by a blood sample, Mullholand said. In the study, blood samples showed more changes in IPF, which some argue is a more systemic disease than fibrotic hypersensitivity pneumonitis. On the other hand, breath condensate from IPF patients was "actually very similar to controls, but with the [fibrotic hypersensitivity pneumonitis], which we consider as a local pulmonary inflammatory state, was much more highly upregulated," he said.
The study included 101 patients who provided blood samples: 28 healthy controls, 33 IPF patients, and 40 fibrotic hypersensitivity pneumonitis patients. Among them, 10, 21, and 18 persons, respectively, provided exhaled breath condensate.
Along with validation studies, the sphingolipids might point to a mechanistic pathway that can begin to be explored, Mullholand said.
"We've never actually looked at sphingolipids alone. There's all these higher-order lipid profiles. Can we target this, is this part of the disease pathway, or is this a consequence of the disease pathway?" he speculated.