Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the ¹³...

Environmental enteric dysfunction (EED) is a syndrome characterized by epithelial damage including blunting of the small intestinal villi and altered digestive and absorptive capacity which may negatively impact linear growth in children. The ¹³ C-sucrose breath test ( ¹³ C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity, which is thought to be reduced in EED. We previously showed how various summary measures of the ¹³ C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration.

We leveraged SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, a natural 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 curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers.

Test durations of less than 2 hours generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition, ρ had a higher sensitivity.

We recommend 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 CO ₂ production rate. More research is needed to assess these classifiers in target populations.