Mo1981 Reciprocal Regulation of Colonic Epithelial Cell Secretion of Osteoprotegerin by Inflammasome Cytokines

Abstract

Background: Pediatric-onset inflammatory bowel disease (IBD) is significantly increasing in prevalence worldwide. In light of the increasing incidence of IBD and its poorly understood pathogenesis, it is important to develop a simple non-invasive tool to detect patients with IBD. Breath testing is becoming an important diagnostic method to evaluate many disease states. The aim of this study was to analyze exhaled volatile organic compounds to potentially elucidate new pathways involved in IBD pathogenesis and differentiate the breathprints of IBD from healthy controls. Methods: An IRB approved prospective study was conducted at a tertiary center. Patients (age range, 5-21 years) with documented IBD were recruited from the Pediatric Gastroenterology Clinic and healthy controls (age range, 5-21 years) were recruited from the General Pediatrics Clinic. The diagnosis of IBD was confirmed by endoscopic, histologic, and radiographic data. Exhaled breath was collected and analyzed using a selective ion flow tube (SIFT-MS) to identify new markers or patterns of IBD. Results: 117 patients were included in the study (62 with IBD and 55 healthy controls). Routinely analyzed VOCs for SIFT-MS quantification showed significant increases in exhaled isoprene, 1-decene, 1-heptene, 1-octene, and 3-methylhexane in patients with IBD (p value , 0.001) (Table 1). Discriminant analysis via stepwise variable selection of mass scanning ion peak data demonstrated five ion peaks (1-octene, H3O+121+, NO+118+, NO+120+, O2+57+) that classified subjects in a 55 patient training set with no misclassifications (-2 log likelihood 0.172; Wilks' Lambda 0.145 (p , 0.0001)) (Figure 1). The discriminant analysis model was then successfully tested in an independent 62 patient validation cohort with only four misclassifications. Conclusion: Exhaled breath analysis is a promising non-invasive method to distinguish children with IBD from healthy children. Exhaled isoprene, 1-decene, 1heptene, 1-octene, and 3-methylhexane are novel biomarkers that are significantly elevated in the breath of children with IBD as compared to healthy controls. Further analysis of these compounds may help to gain insight into pathophysiological processes and pathways leading to the development of IBD. We provide pilot data to support the hypothesis that a unique breathprint can be demonstrated for IBD in the exhaled metabolome. Table 1. Exhaled VOC concentrations