Breath tests for the assessment of gastroparesis

Introduction

Many providers are often faced with the decision of selecting the best test available from their armamentarium to diagnose gastroparesis. This can be challenging with recent evidence showing poor correlation between symptom relief and gastric emptying . There are currently many options on the market, as discussed in other chapters. The Breath Test for gastroparesis is one of the newer tests for gastroparesis available to practitioners, and therefore, one of the least well known. Given its potential utility and efficacy, the Breath Test may supersede Scintigraphy for diagnosing gastroparesis. This chapter will serve as a review of the history of the Breath Test, how it is applied clinically, and its disadvantages and advantages as it relates to its competitors. It will also provide a basic understanding and describe the current utilization of the Breath Test for diagnosing abnormalities in gastric emptying.

History of breath testing in medicine

Analysis of a patients’ breath for detection of various diseases goes back to the time of Hippocrates, the pioneer of medicine. He asked his students to identify diseases by the smell of a patients breath - for example, the odor of rotten apples suggested diabetic ketoacidosis and a urine like odor to the breath suggested renal failure. In the 1770s, Antoine Lavoisier a French chemist discovered the presence of CO ₂ in breath. The adaptation of these findings into medicine specifically, gastroenterology, began during the latter part of the 19th century. Shortly thereafter, Linus Pauling’s milestone discovered the presence of 250 distinct substances within a single exhaled breath, hence presenting hopeful insight into breath testing , thus considered the starting point in the development of exhaled breath analysis.

The physiology behind breath testing

The exhaled human breath consists of well over 3000 different volatile organic compounds (VOCs), and an entire breath cycle consists of around 500 various VOCs, which are reported in part per million (ppm) or part per billion (ppb) . The exhaled breath has long been considered a “breath-print” which can be as unique a fingerprint, which is commonly used as a personalized key. The basic principle of breath testing is that this uniform and standard ratio of substances excreted in a single breath can only change in certain diseased states. The conventional methods for detecting these changes are based on spectrometry techniques, although recently there has been the introduction of gas sensors . While the pathophysiology and therefore methodology of each available test is different, the basic principle remains the same. This principle is that there are abnormal ratios of a certain compound measured in the exhaled breath when there is altered human physiology. This compound is produced by the metabolization of a substrate either in the intestines or in the liver. The product of this reaction contains the gas which is labeled with the stable isotope (Urea and Gastric Emptying Breath test). In the case of the hydrogen breath test there is no tracer, but the test relies on the principle that hydrogen is only made from bacterial fermentation in the gut. The same applies to methane which is a gas excreted by some but not all patients. The gas produced is then transported to the lungs via the blood stream and from the blood it is exchanged by diffusion though the pulmonary alveolar membrane. This exhaled air can easily and painlessly be obtained and analyzed as seen in Fig. 13.3 .

Nuances to remember regarding this process, would be that the first portion of the patient’s exhalation is dead space whereas the latter portion contains alveolar air which contains most of the valuable information . In addition, the anatomy of all breath tests rely on the appropriate function of multiple organ systems (at least the lung, liver, intestine and stomach) and therefore excludes certain patient populations from its usage. Regardless, the field of breath testing continues to grow enormously with evolving technologies in sampling, sensor design, standardization, and analytical methods breath analysis. This is due in part to its simplicity in application.

Current breath tests in clinical practice for gastroenterology

Breath tests have been an important tool for decades for gastroenterologists to explore a number of prevalent diseases related to the gastrointestinal tract. The most common breath tests used can be subdivided into two categories: The Urea Breath Test and The Carbohydrate Breath tests.

The Urea Breath Test (UBT) is the most accurate and best validated of the currently available breath tests . It is a very well-known tool used to diagnose H pylori since the early 2000s. Many diagnostic methods have been developed over the past 2 decades to detect Helicobacter pylori (H pylori) infection—some invasive (rapid urease test, histology, culture, and polymerase chain reaction) because they cannot be performed without endoscopy, and others non-invasive (serology, UBT and more recently, fecal H pylori antigen). The UBT relies upon the oral administration of urea labeled with ¹³ C to identify urease, an enzyme produced in large amounts by H pylori. Urease cleaves the labeled urea to ammonia and labeled bicarbonate, which is subsequently converted to labeled carbon dioxide that is then measured in exhaled breath. The ratio of carbon dioxide would therefore be increased given to its increased production by the bacteria.

The Carbohydrate Breath Test takes advantage of different naturally occurring substrates to assess orocecal transit, carbohydrate malabsorption, or to diagnose patients with small intestinal bacterial overgrowth (SIBO) . To effectively evaluate these disorders the testing depends on the ability of intestinal bacteria to metabolize various carbohydrate substrates (glucose, lactulose and fructose) by releasing hydrogen and/or methane and resulting in the release of quantifiable levels of these gases in exhaled air from the lungs .

The Lactulose Hydrogen Breath test can be used to diagnose Oro-cecal Transit Time, SIBO and lactose intolerance . The Glucose breath test has become more utilized for the diagnosis for SIBO, due to its increased sensitivity. Under normal physiological conditions, glucose is readily absorbed in the small intestine however if there is presence of bacterial overgrowth the flora ferments the glucose prior to it being absorbed. Hence, a breath test showing an inappropriate rise in the hydrogen after consumption of a meal is consistent with the diagnosis of SIBO. The Lactose Breath test uses the principle that the disaccharide is metabolized by the brush border enzyme lactase to glucose and galactose . Reduction or absence of this enzyme leads to excessive exposure of the colon to lactose, where fermentation can result in excessive gastrointestinal symptoms. Fructose is a naturally occurring monosaccharide found in fruits as well as in the disaccharide sucrose. The Fructose breath test is performed to evaluate fructose intolerance. Malabsorption of fructose can lead to its fermentation in the large bowel by the natural flora.