Authors
Hannah Van Wyk, Gwenyth O Lee, Robert J Schillinger, Christine A Edwards, Douglas J Morrison, Andrew F Brouwer
Publication date
2024
Journal
medRxiv
Pages
2024.05. 01.24306704
Publisher
Cold Spring Harbor Laboratory Press
Description
Background
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 13C-sucrose breath test (13C-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 13C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration.
Methods
We leveraged 13C-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.
Results
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.
Conclusions
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 …