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Gastric Motility Breath Test Background


It has been estimated that symptoms of functional gastrointestinal disorders, those without noticeable structural, infectious, or biochemical cause, occur to some degree in nearly one quarter of all individuals who are otherwise healthy (1,2). Of those who seek treatment, many are diagnosed with non-ulcer dyspepsia (NUD), endoscopy-negative gastroesophageal reflux disease (GERD), and irritable bowel syndrome. These functional disorders are often caused or exacerbated by gastrointestinal motility disturbances or gastroparesis (delayed gastric emptying). The non-specific nature of symptoms often requires gastric emptying to be measured objectively.

Gastric scintigraphy is currently the established procedure for monitoring solid and liquid phase gastric emptying. This technique monitors gastric emptying directly by measuring the transit time of a radiolabeled test meal. The test meal is labeled with a gamma emitting marker prior to ingestion. A gamma camera positioned over the abdomen monitors the change in signal as the test meal is digested.

Breath tests employing stable isotopes offer an alternative to scintigraphic techniques for the measurement of gastric emptying. The 13C-octanoate breath test (OBT) has been shown to measure solid phase gastric emptying and correlates with scintigraphic emptying of an egg meal (3).  In this test, 13C-octanoate is mixed into an egg and baked into a meal at the clinical site.  Metabolic Solutions has been active in developing a commercially viable alternative to the 13C-octanoic acid breath test.  Widespread use of the OBT has not occurred because it is not clinically practical due to the inconvenience and lack of uniformity of cooking the egg-based test meal and the demanding time requirement for breath collection. Our research efforts have resulted in a product we call the Gastric Motility Breath Test (GMBT). The GMBT uses an easy to prepare, low-fat muffin meal along with Metabolic Solutions simple breath collection system to provide a convenient and reliable means to monitor solid phase gastric emptying.  This test is a significant advancement in promoting rapid and successful diagnosis for individuals suffering from motility disorders.

Principle of the Gastric Motility Breath Test

A muffin test meal is labeled with 13C-octanoate and administered after an overnight fast. Octanoic acid is a naturally occurring eight-carbon, medium chain fatty acid (MCFA) typically found in butter as an ester.  MCFAs are absorbed by the small intestine and rapidly transported to the liver bound to serum albumin. In the liver, MCFAs freely enter the mitochondria where they are oxidized to CO2. This process is depicted below:


GMBTPIC.gif (62683 bytes)

Gastric emptying is estimated by monitoring the appearance of 13CO2 in breath subsequent to ingestion and metabolism of 13C-octanoate. Mathematical analysis of the 13CO2 appearance in breath reveals estimates of gastric emptying parameters.  The octanoic acid breath test is an indirect measure of gastric emptying because the 13CO2 appearance curve reflects the sum influence of gastric emptying, digestion, absorption, and metabolism. However, the metabolic processing of octanoate is rapid and reproducible, thus delays in emptying are due to differences in gastric motility.

Limitations of Current Gastric Emptying Tests

There are significant limitations with scintigraphy that prevent its frequent use.  A scintigraphic examination costs approximately $1000; requires access to expensive equipment and highly trained personnel; and exposes patients to ionizing radiation.  In addition, due to the nature of the test procedure, the instrument is only capable of performing a few scintigraphies per day.  As a result, scintigraphy is impractical for monitoring the course of treatment and is not an attractive diagnostic option.

The GMBT has several advantages over scintigraphy:

  •  no radioactivity;
  •  the test can be administered at any location;
  •  only limited medical training is required to administer the test;
  •  lower cost;
  •  it can be repeated as necessary to monitor treatment, and
  •  the results are operator independent and will not vary among locations.
Although the principle of the GMBT is biochemically similar to the Octanoate Breath Test described by Ghoos (3), it improves upon the original concept because it replaces the egg meal with a standardized, easy to prepare muffin meal.  For the egg-based tests, the yolk and egg white are first separated because the tracer is only readily solubilized in the yolk.  The octanoic tracer is added to the yolk, which is then beaten.  The egg white is added back and again beaten, followed by cooking by stove top/burner. In comparison, the GMBT uses a standardized muffin meal requiring just the addition of water to a powdered mix, stirring of the contents, and microwaving for 1-2 minutes.

The GMBT has several advantages over the Octanoate Breath Test with egg-based meal:
  •  standardization of the meal (eggs vary in caloric content, size and  composition)
  •  ease of preparation
  •  is operator independent
  •  standardized cooking conditions allows valid inter-clinical site
     comparisons

References

(1) Parkman, H.P., M.A. Miller and R.S. Fisher. Sem. Nucl. Med. 1995; 25:289-305.
(2) Horowitz, M. and R.J.L. Fraiser. Scand. J. Gastroenterol. 1995; 30:7-16.
(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.

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