Metabolomic profiling of extraesophageal reflux disease in children

Although respiratory symptoms in children are often attributed to gastroesophageal reflux disease, establishing a clear diagnosis of extraesophageal reflux disease (EERD) can be challenging, as there are no sensitive or specific EERD biomarkers. The aim of this study was to evaluate the metabolite profile in bronchoalveolar (BAL) fluid from children with suspected EERD and assess the impact of reflux treatment on these metabolites. In this prospective pilot study, we performed nontargeted global metabolomic profiling on BAL fluid from 43 children undergoing testing with bronchoscopy, upper endoscopy, and multichannel intraluminal impedance with pH (pH-MII) for evaluation of chronic respiratory symptoms. Twenty-three (54%) patients had an abnormal pH-MII study. Seventeen (40%) patients were on proton pump inhibitors (PPIs) for testing. Levels of histamine, malate, adenosine 5'-monophosphate, and ascorbate were significantly lower in subjects with abnormal pH-MII studies compared to those normal studies. Furthermore, in children off PPI therapy, those with abnormal pH-MII studies had robust increases in a number of glycerophospholipids within phospholipid metabolic pathways, including derivatives of glycerophosphorylcholine, glycerophosphoglycerol, and glycerophosphoinositol, compared to those with normal pH-MII studies. These findings offer insight into the impact of reflux and PPIs on the lungs and provide a foundation for future studies using targeted metabolomic analysis to identify potential biomarkers of EERD.