Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the13C-sucrose breath test.

Abstract

The13C-sucrose breath test (13C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity and is a promising test for SIM deficiency, which can cause gastrointestinal symptoms, and for intestinal mucosal damage caused by gut dysfunction or chemotherapy. We previously showed how various summary measures of the13C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration.
Methods: We leveraged13C-SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, an SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier, ρ, and three empirical classifiers (cumulative percent dose recovered at 90 minutes (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic (ROC) curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers.
Results: Test durations of less than 2 hours generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest ROC area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition, ρ had a higher sensitivity.
Conclusions: We recommend13C-SBT tests run for at least a 2-hour duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of CO2production rate. More research is needed to assess these classifiers in target populations.&#xD.