A clinical laboratory test developed, validated, and performed at NewYork-Presbyterian and Columbia helps identify a biomarker of aspiration from gastroesophageal reflux, a risk factor for lung injury and allograft dysfunction, providing an early warning of complications in lung transplant recipients.
The test detects the presence of bile acids in the airways — a sign of gastrointestinal reflux-related aspiration (GRASP), which is associated with lung injury and allograft rejection, among other negative outcomes. Although gastroesophageal reflux can be diagnosed using esophageal pH testing, there has been no gold standard test to diagnose aspiration of refluxed gastrointestinal juices in the lungs, making early intervention difficult for transplant pulmonologists.
“Aspiration of gastrointestinal juices as a consequence of gastroesophageal reflux has been a diagnosis by exclusion, with the assumption that if you have acid esophageal reflux you may aspirate the refluxed gastric juices,” says Frank D’Ovidio, M.D., Ph.D., professor of surgery in the Department of Surgery at Columbia, and lung transplant and general thoracic surgeon at NewYork-Presbyterian and Columbia, who has been studying and validating this specific biomarker and spearheaded the test’s development. “Until now there has been no specific diagnostic tool to document aspiration of gastrointestinal juices. This clinical tool facilitates a more precise medical diagnosis and helps triage the management of our patients.”
Testing has already helped inform care for patients at NewYork-Presbyterian and is now available as a service for other lung transplant centers.
“Antacids, proton pump inhibitors, histamine-2 blockers, and other gastric acid-reducing medications change the pH of gastric juices to treat heartburn and esophagitis from acid reflux, but they do not eliminate the reflux of other gastrointestinal juices, such as bile acids, which may be inadvertently aspirated — particularly at night while sleeping, causing lung injury,” says Dr. D’Ovidio.
Gastrointestinal reflux-related aspiration (GRASP) is associated with lung injury and is a predictor of lung dysfunction. GRASP occurs when gastrointestinal juices reflux into the esophagus and enter the upper airway and lungs. Testing for the presence of bile acids in the airways is diagnostic for GRASP.
Large airway bronchial washing (LABW) is a routine post-transplant surveillance procedure in which sterile saline is washed into parts of the lung airways through a bronchoscope and suctioned back out. The liquid sample collected during LABW is then tested for bile acids using liquid chromatography and tandem mass spectrometry.
Developing the Clinical Assay
Development at Columbia began when Dr. D’Ovidio approached clinical laboratory researchers in search of an assay that could measure bile acids from bronchial washings, which is performed during routine surveillance bronchoscopies for lung transplant recipients. He wanted to confirm precisely his original translational research findings that bile acids detected in the airways are a biomarker for gastroesophageal reflux-related aspiration and a predictor of lung dysfunction; he also sought to eventually build an accurate and accessible diagnostic clinical test for GRASP.
After trying several types of bile acid assays, Serge Cremers, Ph.D., PharmD, professor of pathology and cell biology and medicine in the Department of Pathology and Cell Biology at Columbia and co-director of the Clinical Pharmacology and Toxicology Laboratory, and his colleagues determined that mass spectrometry, an analytical technique that can measure the molecular weight of sample components, was specific and sensitive enough to detect trace amounts of bile acids in bronchial washings. A research mass spectrometry-based assay was first developed in the Biomarkers Core Laboratory at Columbia’s Irving Institute for Clinical and Translational Research and subsequently transferred to the Clinical Pharmacology and Toxicology Laboratory.
Once Dr. D’Ovidio completed clinical studies through the Biomarkers Core Laboratory and discovered that a subset of bile acids, known as conjugated bile acids, could accurately predict lung injury, Dr. Cremers and team began to redevelop the assay specifically for patient care. “With research assays, you collect all the samples and run them in one batch, and then you may not run it again for another year,” explains Dr. Cremers. “With a clinical assay, we run samples every day or every week, which necessitates a different, more rigorous validation than the validation of the mass spectrometry-based assay developed by the Biomarkers Core Lab for research.”
It would take a few years to develop a robust clinical assay, which obtained New York State regulatory approval as a laboratory-developed test in June 2025, an effort that was led by Alex Lyashchenko, M.D., Ph.D., assistant professor of pathology and cell biology in the Department of Pathology and Cell Biology at Columbia, pathologist at NewYork-Presbyterian and Columbia, and co-director of the Clinical Pharmacology and Toxicology Laboratory. “At New York-Presbyterian and Columbia, we get to collaborate with our clinical colleagues to develop tests that are not yet routine but have the potential to be very useful for clinical care in the future,” says Dr. Lyashchenko.
Laboratory supervisor Sandye Chauncey runs bronchial washing samples through the assay in the Clinical Pharmacology and Toxicology Laboratory at Columbia.
Expanding Access to Bile Acids Testing
Since receiving regulatory approval, the NewYork-Presbyterian and Columbia lung transplant team has been able to send samples from bronchial washings to the onsite lab, and results can typically be expected within one week. Knowing that a transplant patient’s bronchial washing is positive for bile acids gives clinicians an opportunity to address the aspiration of gastroesophageal reflux early, such as through a fundoplication, and potentially prevent lung injury or allograft failure. “The difficulties posing an indication for fundoplication often have led to delays in getting the treatment. But early fundoplication has been shown to be greatly protective against lung dysfunction and chronic rejection,” says Dr. D’Ovidio.
Other transplant centers can also send samples to NewYork-Presbyterian and Columbia for analysis, and the team welcomes the opportunity to share their knowledge with institutions who are interested in establishing their own clinical assay. “Right now, we’re the only ones in the world set up to do this test in support of patient care, but you always want peers to compare your data and results with,” says Dr. Cremers.
While lung transplant recipients are the current target patient population, Dr. D’Ovidio believes the assay will be useful for other lung diseases. “Looking ahead, I believe this new clinical test will also help patients with interstitial lung diseases and pulmonary fibrosis, cystic fibrosis, and chronic obstructive pulmonary disease, whose outcomes are known to be associated with presumed aspiration of gastroesophageal reflux,” he says.
“We’re very receptive to our clinicians coming to us and saying that they think a certain test would be useful for patient care, because we have the experience to get it properly validated and approved,” adds Dr. Lyashchenko. “Developing this tool is representative of what our lab does.”
