A stable isotope breath test with a standard meal for abnormal gastric emptying of solids in the clinic and in research

Abstract

Background & aims: The aim of this study was to validate a [13C]-Spirulina platensis gastric emptying (GE) breath test (GEBT) with a standardized meal.

Methods: Thirty-eight healthy volunteers and 129 patients with clinically suspected delayed GE underwent measurements at 45, 90, 120, 150, 180, and 240 minutes after a 238 kcal meal labeled test with 100 mg [13C]-S platensis and 0.5 mCi 99mTc. We established normal ranges for scintigraphy with this test meal, intraindividual and interindividual coefficients of variation (COVs), and the ability of the [13C] GEBT breath percent dose excreted *1000 values to predict scintigraphic half-life and to categorize GE as delayed, normal, or accelerated.

Results: In health, the 10th and 90th percentiles of half-life for scintigraphic GE with this meal were 52 and 86 minutes; intraindividual COVs for scintigraphy and the GEBT were, respectively, 31% and 27% at 45 minutes, 17% and 21% at 90 minutes, 13% and 16% at 120 minutes, 10% and 13% at 150 minutes, and 8% and 12% at 180 minutes. Interindividual COVs at each time for the [13C] GEBT and scintigraphy were typically approximately 1%-4% lower than intraindividual COVs. Individual breath samples at 45, 150, and 180 minutes predicted GE category; at 80% specificity, 45- and 180-minute samples combined were 93% sensitive to identify accelerated GE, and 150- and 180-minute combined were 89% sensitive for delayed GE.

Conclusions: [13C]-S platensis GEBT is as reproducible as scintigraphy; imprecision with both tests reflects physiologic variation. With 4 breath samples, this method with an off-the-shelf meal is valid to assess GE in clinic and in research.

Figure 1

A. Summary of gastric emptying results by t1/2 group in 129 subjects with clinically suspected delayed gastric emptying. Data show mean ± SD. B. This figure illustrates ¹³CO₂ enrichment of breath excreted over 3 hours (right Y-axis κPCD × 10⁻²), as well as the observed proportion emptied by the stomach by scintigraphy (left Y-axis) and the predicted gastric emptying based on the mathematical formulae and the ¹³CO₂ excretion measured.

Figure 2

Plot of the first canonical variates (linear combinations with maximal correlation) with scintigraphic variate on the Y-axis and the [¹³C]-Spirulina platensis GEBT breath kPCD variate on the X-axis. Specifically, the first canonical variate for the GE proportions (Y-axis in figure) has a strong (negative) relationship with the scintigraphically based t ½ values (Spearman correlation of −0.82, p<0.001). The first canonical variate of the kPCD values (X-axis in figure) was also strongly related to these t ½ values (Spearman correlation of −0.73, p<0.001). Since more delayed GE corresponds to larger t ½ values, the correlation of these canonical variates with t ½ values is negative, reflecting the propensity of the more delayed GE subjects in the lower left quadrant and the more accelerated GE subjects in the upper right quadrant.

Figure 3

Scatterplot of the scintigraphic measured gastric emptying t ½ values (Y-axis) versus the breath test estimated t ½ values (X-axis) obtained from linear interpolation of breath test predicted GE proportions. The dotted line shows X=Y.

Figure 4

Bland-Altman plot of the differences between scintigraphic measured t ½ values and breath test estimated t ½ values (Y-axis) versus the average of the two t ½ values (X-axis) in each subject. Note that subjects with t ½ values greater than 240 minutes by scintigraphy are not used.

Figure 5

ROC curve for the detection of delayed gastric emptying with [¹³C]-Spirulina platensis GEBT measurements relative to the scintigraphic measurement of gastric emptying. Note that the performance characteristics are uniformly excellent even with a single breath sample at 150 minutes, but the sensitivity reaches 89% at 80% specificity when the 180 minute sample is also included. The AUC for the combined 150 and 180 minute samples was 0.893. Note also that the 45 minute sample adds little to the accuracy of determination of the GEBT for categorizing delayed GE above the accuracy of the combined 150 and 180 minute breath samples. Combining the three time points (45, 150 and 180 minutes) resulted in an AUC of 0.890.

Figure 6

ROC curve for the detection of accelerated gastric emptying with breath test measurements relative to the scintigraphic measurement of gastric emptying. Note the proportion emptied at 45 minutes provides fair sensitivity and specificity and the best performance is with all three breath samples. However, the 45 minute breath sample in combination with the 180 minute sample yielded a sensitivity of 93% at 80% specificity. The AUC for the combined 45 and 180 minute samples was 0.895. Combining the three time points (45, 150 and 180 minutes) resulted in an AUC of 0.902