Oxygen-18 stable isotope of exhaled breath CO2 as a non-invasive marker of Helicobacter pylori infection†
We report for the first time the time-dependent excretion kinetics of 18O/16O isotope ratios of CO2 in exhaled breath samples using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method for the detection of Helicobacter pylori (H. pylori) infection in human stomach. We observed large differences in the oxygen-18 isotopic fractionations of breath CO2 between H. pylori positive and negative individuals in response to orally administered, both unlabelled and labelled 13C-enriched urea, suggesting a potential link between H. pylori infections and the 18O-isotopic exchange in exhaled breath. An optimal diagnostic cut-off point of 18O/16O isotope ratios of breath CO2 for the presence of H. pylori infection was determined to be 1.92‰ using the receiver operating characteristic curve (ROC) analysis, which exhibited both diagnostic sensitivity and specificity of 100% with an accuracy of 100%. Moreover, the methodology of monitoring 18O in breath CO2 manifested both positive and negative predictive values of 100%, demonstrating excellent diagnostic accuracy and suggesting that breath C18O16O could be used as a potential marker for the identification of H. pylori infections. Our findings also suggest that monitoring the 18O/16O isotope ratios of breath CO2 is a valid and sufficiently robust novel non-invasive approach for the accurate and specific detection of H. pylori infection in real-time, which may open new perspectives in the molecular diagnosis of H. pylori infection for large-scale screening purposes, early detection and follow-up of patients.