Metabolomic changes in exhaled breath condensate as biomarkers of extraesophageal reflux disease
Lisa Mahoney, MD
BACKGROUND: Children presenting with cough, wheezing, stridor, and pneumonia are frequently treated with acid suppression therapy because general pediatricians, gastroenterologists, pulmonologists and otolaryngologists believe these symptoms may be related to gastroesophageal reflux disease (GERD). This empiric treatment has become mainstream because of a lack of sensitive diagnostic tests for these extra-esophageal symptoms, which has resulted in misdiagnosis and overtreatment.
GAP: Current diagnostic tests for GERD (endoscopy, pH-metry, impedance testing) lack the sensitivity needed to diagnose extraesophageal reflux disease (EERD). The goal of this research study is to develop a sensitive, noninvasive diagnostic test that directly assesses the impact of gastroesophageal reflux on the lung, a significant improvement over current tests which focus only on esophageal reflux burden.
HYPOTHESIS: Our hypothesis is that there is a unique metabolomic exhaled breath condensate (EBC) profile that can be measured non-invasively and can accurately diagnose EERD.
METHODS: In cross-sectional studies in children ages 5-18 with respiratory symptoms and suspected EERD, we will validate the EBC metabolomics profiles against the results of gold standard tests for GERD (validated questionnaires, pH-impedance testing, and endoscopy) and against metabolomic profiles in fluid obtained during bronchoscopy. In a longitudinal study, we will also collect EBC samples in patients before and after initiation of proton pump inhibitors (PPIs) to detect changes in the lung metabolome over time.
IMPACT: The potential impact of these proposed studies is great, as we seek a way to noninvasively diagnose EERD, a common and very costly pediatric disease. This, in turn, may decrease the utilization of invasive diagnostic procedures in children, as well as reduce unnecessary and expensive PPI trials, which have been associated with significant adverse effects in recent research studies.