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Gastric Motility Breath Test Validation |
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Binding of Tracer to Muffin
The amount of tracer remaining associated with the muffin
meal after incubation in gastric fluid has been determined
to be greater than 95%. These in vitro results show
that 13C-octanoate is bound to the muffin during
microwave cooking and is suitable to trace solid phase
gastric emptying.
Determination of Meal Size
The test meal must challenge gastric motility. The
size of the test meal is important because it determines
the ability of the test to differentiate individuals with
impaired motility from normals. Electrogastrography
(EGG) was employed as an independent measure of gastric
motility. EGG records the gastric myoelectrical
activity using cutaneous electrodes. The half emptying
time (T½) was compared to the EGG P/F power ratio obtained
for two different sized muffins (250 and 350 calories)
in the fasting and postprandial states (1).
The results of the EGG analysis showed that the P/F power
ratio was significantly higher with the 350 calorie muffin.
Secondly, T½ was significantly longer for the 350 calorie
meal. Most importantly, the T½ of the 350 calorie
meal was significantly correlated with the P/F power ratio
(r=0.926, p<0.01). However, there was no correlation
between T½ and the P/F power ratio for the 250 calorie
muffin. These results showed that the 350 calorie
muffin meal is able to better stimulate gastric motility
than the smaller sized meal.
Comparison to Scintigraphy
A double-labeled muffin study was conducted to determine
how well the GMBT correlated with the “gold standard”
gastric emptying scintigraphy (GES) (2). Added to the
muffin mix was 13C-octanoate and technetium-99m
sulfur colloid. The meal was ingested also with water
labeled with indium-111DTPA. Ten (10) normal subjects
(6 females, 4 males; age range: 18-62 years) without gastrointestinal
symptoms and twenty-three (23) patients (19 females, 3
males; age range 20-72 years) with dyspeptic symptoms
of nausea, vomiting, early satiety, upper abdominal pain
and/or discomfort, or abdominal bloating underwent simultaneous
GES and the GMBT. Scintigraphic images (anterior and posterior)
for Tc-99m and In-111 were obtained with a gamma camera
immediately following completion of the meal for four
hours. Breath samples were collected every 15 minutes
for 6 hours for 13C-carbon dioxide analysis.
Each scintigraphic image obtained was analyzed to determine
the gastric counts. The gastric region of interest was
manually drawn around the total stomach at each time interval.
A geometric mean of the gastric counts was used to correct
for depth changes [geometric mean counts = square root
(anterior counts x posterior counts)]. The counts were
corrected for radioisotope decay. The data was expressed
as percent of the initial meal remaining in the stomach
versus time and fitted to a modified power exponential
function. The breath data was expressed as the percent
dose exhaled/hour and cumulative percent of the dose over
time. Curves fitted to the percent dose/hour and cumulative
percent of dose provided constants to calculate the gastric
emptying parameters T½ and Tlag according to the method
of Ghoos et al. (3).
In normal subjects, the T½ for the GMBT significantly
correlated with T½ solids by GES (r=0.86; p<0.001),
but did not correlate with T½ liquids by GES (r=0.08;
p=0.83). In dyspeptic patients, the GMBT also significantly
correlated with the GES T½ solids (r=0.86; p<0.001)
and GES T½ liquids (r=0.75; p<0.001). Combining the
data from normal and dyspeptic patients, there was a significant
correlation of the GMBT with GES T½ solids (r=0.86; p<0.001).
The equation of the regression line for the T½ solids
by GMBT is GES = 0.49 x (GMBT) – 1.34. This equation
now relates the GMBT to scintigraphy. The approximate
doubling of the T½ with the GMBT is due to the processing
time of octanoate. We can apply this regression equation
to equate the two tests.
Using the upper limit of normal (95% confidence interval),
delayed gastric emptying was identified in 7 of 33 subjects
by scintigraphy. The sensitivity and specificity of the
GMBT to identify delayed gastric emptying was 86% and
96% , respectively.
In conclusion, we found a significant correlation between
the GMBT, using an easilyprepared muffin meal and GES
of solids. We further showed a strong correlation between
the half emptying times of GES with both the muffin
meal and the standard egg meal used for scintigraphic
gastric emptying studies suggesting that the simple
muffin meal is a valid substitute for the egg meal to
measure gastric emptying.
Determination of Normal Range of GMBT
One hundred individuals without motility symptoms were
administered the GMBT to understand the inter-subject
variation and normal range of the test (4). Using
the regression equation found above, we determined that
the normal range with the GMBT test was 40 to 90 minutes.
A histogram plot of the results showed a normal distribution.
The Anderson-Darling Normality Test had an A squared value
of 0.988 (p=0.013). The mean for these subjects
was 66 minutes with a standard deviation of 11 minutes.
This mean and standard deviation compares favorable to
results reported by Ghoos in 42 normals (mean = 72 and
SD=22). The standard deviation for normal motility
measured with the GMBT was about half encountered with
the egg-based meal. We attribute this lower variability
to the standardization of the GMBT meal and the ease of
test administration that minimizes testing protocol deviations
and thus improves the reliability of the test.
Normal Distribution of GMBT Test
Click to enlarge figure
Pharmacological Modulation
Pharmacological modulation of gastric
emptying to further validate the GMBT has been performed
(4). Two drugs with a known influence on gastrointestinal
motor activity were used, erythromycin, which accelerates,
and propantheline, which delays gastric emptying.
Forty (40) volunteers were administered a GMBT test
to determine T½ rates. Volunteers were randomly
selected to receive 200 mg erythromycin intravenously
or 30 mg propantheline orally, just prior to the GMBT.
Erythromycin caused a significant reduction in the gastric
half-emptying time. Propantheline, an anticholinergic
drug, significantly delayed gastric half-emptying times.
The results of pharmacological modulation are presented
below:
Table 1: Effect of erythromycin on the GMBT.
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Treatment
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T½ (min) |
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Control
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69 ± 17 |
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Erythromycin
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48 ± 8.7 |
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t test Significance
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p<0.0001 |
Values shown are mean ± standard deviation
Table 2: Effect of propantheline on the GMBT.
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Treatment
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T½ (min) |
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Control
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69 ± 17 |
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Propantheline
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92 ± 38 |
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t test Significance
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p=0.0072 |
Values shown are mean ± standard deviation
These results demonstrate that the GMBT can accurately
predict stimulation or delay of modulated gastric emptying
by drugs.
Conclusions
These results show a significant correlation
between the GMBT and gastric scintigraphy for solids
using an easily prepared, low-fat, standardized muffin
meal. The GMBT is both sensitive and specific
to delayed gastric emptying in dyspeptic patients.
The GMBT also predicts stimulation or delay of gastric
emptying caused by drug administration. The performance
of this test, combined with the significantly decreased
cost, decreased test and personnel time, and simpler
and more efficient instrumentation requirements, makes
the GMBT a very attractive new methodology for assessing
gastric motility disorders both in the pharmaceutical
industry and ultimately in routine clinical practice.
References
(1) Gonlachanvit, S., W.D. Chey, K.J. Goodman and H.P.
Parkman. Dig. Dis. Sci. 2001; 46:2643-2650.
(2) Bromer, M.Q., S.B. Kantor, D.A. Wagner, L.C. Knight,
A.H. Mauer and H.P. Parkman. Dig. Dis. Sci. 2002; 47:1657-1663.
(3) Ghoos, Y.F., B.D. Maes, B. Geypens, G. Mys, M.I. Hiele,
P.J. Rutgeerts and G. Vantrappen. Gastroenterology 1993;
104:1640-1647.
(4) Wagner, D.A., D.L. Bolt, K.G. Goodman and M. Rosenberg
(unpublished data). |
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