Combined Lactulose H2-breath Test With Abdominal Imaging

Overview

Hydrogen (H₂) breath tests serve several purposes. (i) detect malabsorption of carbohydrates such as lactose and fructose, (ii) measurement of oro-caecal transit time (iii) associate hydrogen production with the onset of abdominal symptoms like bloating, flatulence, pain, and diarrhea (which indicates carbohydrate intolerance), and (iv) diagnose small intestinal bacterial overgrowth (SIBO). It is important to distinguish between carbohydrate intolerance and SIBO because their treatments differ significantly. Carbohydrate intolerance is typically managed through dietary restrictions, while SIBO requires antibiotic therapy. However, recent guidelines have questioned the accuracy of hydrogen breath tests in diagnosing SIBO due to variability in OCTT measurements. This limitation can be addressed by combining H₂ breath tests with imaging techniques such as scintigraphy, which independently confirm OCTT. When this combined approach is used, SIBO is diagnosed if the rise in breath H₂ occurs before the contrast agent appears in the large bowel. Despite its benefits, this combined method faces organizational and financial challenges that limit its routine clinical use. This retrospective cohort study aims to assess the clinical performance of a cheap and simple test that combines a 20g lactulose H₂ breath test with simple radiographic abdominal imaging to assess OCTT, SIBO, and carbohydrate tolerance. The novel innovation in this method is to confirm oro-caecal transit by taking an X-ray of the abdomen when H₂ production increases during the examination. If the contrast agent is not visible in the cecum when H₂ rises, this indicates the presence of SIBO. Conversely, if the contrast agent is present in the cecum at that time, it confirms normal OCTT, and any abdominal symptoms occurring after this point support a diagnosis of carbohydrate intolerance. If the method is proven to be valid, then this simple test will greatly facilitate the accurate diagnosis of SIBO and carbohydrate intolerance, allowing for more appropriate treatment decisions.

Carbohydrate malabsorption can be detected by hydrogen (H2) breath tests because this gas is not generated by human cells but is derived exclusively through anaerobic fermentation of carbohydrates by enteric microflora. Increased concentrations of this biomarker in breath after oral ingestion of a fermentable carbohydrate indicates that this substrate has not been fully absorbed by the small bowel and has come into contact with saccharolytic bacteria. Several substrates have been used in H2 breath tests. The aims of these tests include (I) detection of carbohydrate malabsorption of lactose and fructose and other substrates that are variably absorbed in the small bowel, (II) measurement of the time interval between ingestion of an unabsorbable carbohydrate, such as lactulose, and its contact with colonic bacteria in the cecum (oro-cecal transit time, OCTT), and (III) association of H2 gas production with onset of abdominal symptoms like bloating, flatulence, abdominal pain and diarrhea, i.e. carbohydrate intolerance (IV) diagnosis of small intestinal bacterial overgrowth (SIBO) by an "early rise" (e.g.; \<90 minutes) in H2 after ingestion of a test substance (e.g. glucose or lactulose), due to abnormally high concentrations of bacteria in the small intestine. The distinction between carbohydrate intolerance and SIBO is important because treatment of the two conditions is different. The former is most often managed by dietary restriction, whereas the latter is treated by antibiotics. Recent guidelines and editorials have questioned the accuracy of H2 breath tests in the detection of SIBO primarily due to high variation in measurements of OCTT. In particular, rapid OCTT leading to an early rise in H2 after ingestion of a substrate can lead to a false positive diagnosis of SIBO and treatment with inappropriate medication. This limitation can be addressed by combining H2 breath tests with scintigraphic imaging that provides an independent assessment of OCTT. When this methodology is applied, SIBO is diagnosed when there is an increase in breath H2 before scintigraphic contrast appears in the large bowel. However, there are important organizational and financial barriers to implementation of this approach in routine clinical practice. This retrospective cohort study reports the performance of a cheap and simple test that combines a 20g lactulose H2 breath test with radiographic abdominal imaging to assess OCTT, SIBO, and carbohydrate tolerance. The novel innovation in this method is to confirm oro-caecal transit by taking an X-ray of the abdomen when H2 production increases during the examination. If contrast agent is NOT visible in the caecum when H2 increases, then SIBO is present. Otherwise, if contrast agent is present in the caecum, then results confirm OCTT and the occurrence of abdominal symptoms after this time is consistent with the diagnosis of carbohydrate intolerance. The rationale of using 20g lactulose in this investigation is based on the results of a series of studies from the principle investigator and others that showed (i) H2 breath test results after ingestion of 20g lactulose are statistically not different to those after ingestion of 20g lactose in a patient with lactase deficiency. (ii) The 20g lactulose nutrient challenge test can identify patients with carbohydrate intolerance (i.e. lactulose is a representative FODMAP) especially in patients with visceral hypersensitivity, a common feature of patients with irritable bowel syndrome (IBS). (iii) a dose response relationship between the amount of substrate ingested and the likelihood of symptoms occurring in health and disease, with IBS patients statistically significantly more likely to have symptoms after ingestion of 20g indigestible carbohydrate compared to healthy controls (OR \>3). (iv) pilot data that suggests patients with SIBO identified using combined 20g lactulose H2 breath test with abdominal imaging have more severe symptoms than patients with food intolerance without SIBO and also report an improvement in abdominal symptoms after treatment with a non-absorbable antibiotic (rifaximin) which does not occur in patients without SIBO.