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 CO2 production rate. More research is needed to assess these classifiers in target populations.

The authors have declared no competing interest.

This project was funded through the International Atomic Energy Agency (IAEA) coordinated research projects E4.10.16 and E430336, United States National Science Foundation (NSF) grant DMS1853032, and United States National Institutes of Health (NIH) grant K01AI145080. The NSF and NIH were not involved in study design; collection, analysis, and interpretation of data; writing of the report. The IAEA was involved in study design of the data collection. The supporting sources did not have restrictions regarding publication.

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Data described in the manuscript (Data_MLE.csv) are made publicly and freely available without restriction at https://doi.org/10.5281/zenodo.8387995.

https://doi.org/10.5281/zenodo.8387995