CLINICIANS GUIDE TO HYDROGEN BREATH TESTING HELP YOUR PATIENTS MANAGE IRRITABLE BOWEL SYNDROME AND FOOD INTOLERANCES

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CLINICIANS GUIDE TO HYDROGEN BREATH TESTING HELP YOUR PATIENTS MANAGE IRRITABLE BOWEL SYNDROME AND FOOD INTOLERANCES Introduction Hydrogen (H2) breath testing is used to investigate patients with irritable bowel syndrome (IBS), food intolerances and suspected bacterial overgrowth syndromes. Breath hydrogen tests provide clinicians with a scientific basis to plan low FODMAP diets for their patients and to advise on dietary exclusions. The tests are now used routinely in gastroenterology, are simple, non-invasive and are performed after a short period of fasting. This clinician s guide addresses the principles behind the tests, how they are conducted, appropriate patient selection and result interpretation. Why test for breath Hydrogen? In humans, hydrogen gas is produced by bacterial fermentation of carbohydrates that are incompletely absorbed in the small intestine and delivered undigested to the large intestine. Hydrogen, methane, short chain fatty acids, acetate and sulfides are the byproducts of the process and may be responsible for intestinal bloating, abdominal pain, wind, diarrhoea and other reported symptoms of irritable bowel syndrome (IBS). Intestinal gas is passed as flatus but also absorbed across the intestinal mucosa into the blood stream. Gas transfer at the lungs allows measurement of expired breath hydrogen. Recently described FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) including lactose, fructose and sorbitol are poorly absorbed in patients with IBS and are strongly implicated in the pathogenesis of symptoms. FODMAPs are not only subject to fermentation and excess gas production but are also highly osmotic drawing fluid into the bowel further altering gut motility. Small intestinal bacterial overgrowth (SIBO) should all be considered in the aetiology of functional gut syndromes. FODMAP s DESCRIPTION DETAILS EXAMPLE FOODS F Fermentable By colonic bacteria O Oligosaccharides Fructans, Galacto-oligosaccharides Wheat, barley, rye, onions, lentils D Disaccharides Lactose Milk, chocolate, ice cream M Monosaccharides Excess Fructose (fructose in excess of glucose) Apples, pears, mangoes, honey A And P Polyols Sorbitol, mannitol, maltiol, xylitol Apples, pears, confectionery COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 48

Breath testing for hydrogen production provides a reliable method of identifying patients with functional gut syndromes associated with carbohydrate malabsorption and those with small intestinal bacterial overgrowth. It is important to note that breath hydrogen is derived wholly from bacterial fermentation; there is no other physiological source of hydrogen in the human body. A small group of test patients (about 10%) may be predominant methane producers. Very little hydrogen is found in the breath of these patients despite active gastrointestinal symptoms. Lactulose testing conducted as part of the recommended panel of tests identifies this cohort. - KEY POINT - Measurement of breath hydrogen accurately reflects intestinal fermentation of incompletely digested or poorly absorbed carbohydrates. Elevated breath hydrogen after ingestion of a specific test agent identifies intolerance and a potential trigger of symptoms. BREATH HYDROGEN ASSESSMENT REFLECTS CARBOHYDRATE MALABSORPTION COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 49

What tests are available? LACTULOSE: Lactulose is not absorbed across the small intestinal mucosa and is used to assess hydrogen production. Lactulose testing also measures small bowel transit time and is utilised to assess bacterial fermentation in the small bowel (bacterial overgrowth) where an early peak in hydrogen production is observed. An absence of H2 production with lactulose indicates predominant methane production, symptom recording in this cohort helps to identify intolerance. LACTOSE: This is used to measure how well the lactase enzyme system is working and investigates lactose intolerance. FRUCTOSE: This is the sugar commonly found in fruits, fruit juices and confectionery. Complex fructose molecules are referred to as fructans and these can be found in onions, lentils and other vegetables. SORBITOL: This is present in common fruits such as apples and pears as well as artificial sweeteners. GLUCOSE: Can be used as an aid in testing for small intestinal bacterial overgrowth (SIBO). The following are a list of carbohydrates used in clinical breath testing. CARBOHYDATE LACTULOSE LACTOSE FRUCTOSE SORBITOL GLUCOSE DEFICIENCY TESTED BACTERIAL OVERGROWTH LACTOSE INTOLERANCE (10-15% Caucasians) FRUCTOSE MALABSORPTION (45% Population) SORBITOL MALABSORPTION (70% with IBS) BACTERIAL OVERGROWTH Who should be tested? Testing should be considered in patients with IBS, specific food intolerances and in those suspected of having small intestinal bacterial overgrowth (SIBO). Bloating, generalised abdominal discomfort, passage of excessive flatus and altered bowel habit identifies patients who may benefit from further analysis. Current data suggests that 45% of the Australian population have fructose intolerance. Lactose intolerance is present in 10-15% of Caucasians and in up to 85% of Asians. Consumption of fructose or lactose in these patients may result in IBS-like symptoms. Patients with IBS commonly have intolerance to FODMAP s including complex fructose molecules called fructans. COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 50

Studies show that up to 75% of patients with IBS experience a significant improvement in symptoms with dietary manipulation. Small intestinal bacterial overgrowth syndromes (SIBO) occurs where there is altered gut transit as seen in some patients with scleroderma and where surgical blind loops exist. SIBO may also be seen in patients with more typical IBS-like symptoms even in the absence of scleroderma or previous surgical history. - KEY POINT - Indications for Testing IBS patients Suspected lactose intolerance Suspected fructose intolerance Suspected small intestinal bacterial overgrowth How is the test performed? A safe and simple hand held gas analyser machine (gastrolyser) is used to detect small amounts of exhaled hydrogen after patients ingest a test dose of carbohydrate. An exclusion diet is followed the evening before the test and a 5 hour fast required. A baseline hydrogen value is taken before test carbohydrates are administered. A standard dose of a specific carbohydrate (fructose, lactose or sorbitol, etc.) is ingested and readings are taken at 20 minute intervals looking for a rise of at least 20 ppm of H2. If there is no increase in breath hydrogen and no abnormal symptoms the test carbohydrate has been completely absorbed. A rise in breath H2 of more than 20ppm indicates incomplete absorption of the test sugar and intolerance. During the analysis symptoms are recorded and must be considered along with the measured hydrogen levels to establish the diagnosis of carbohydrate intolerance. Only one test can be performed per day, a 2-3 day break is required between testing. Testing is non-invasive, takes 2-3 hours, and is safe for all ages over 5 years. Testing may be performed during pregnancy after exclusion of gestational diabetes. Diabetic patients must contact the testing centre before investigation to discuss glycaemic control. COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 51

Which test should be ordered first? Testing should be considered carefully in relation to the clinical history. 1. All testing commences with lactulose. This identifies adequate hydrogen production but also provides information regarding small bowel bacterial overgrowth (early hydrogen peak) and small bowel transit time. 2. For Irritable Bowel Syndrome subsequent testing with fructose and lactose is recommended. Proceed to sorbitol when the above investigations are negative and symptoms prevail. 3. Assessment of small intestinal bacterial overgrowth (SIBO) is made with lactulose. Supplementary testing with glucose may be helpful in these patients. Testing does not exclude other coexisting or independent organic diagnoses. It is important clinicians consider the possibility of peptic ulcer disease, coeliac disease, inflammatory bowel disease, neoplasia, biliary disease, etc. in their management. These diagnoses may require further consideration and evaluation in the same subset of patients referred for breath test analysis. The following algorithm may be of assistance in the clinical workup of Irritable Bowel Syndrome. SYMPTOM AND DIETARY HISTORY CONSIDER FOOD INTOLERANCES CAREFUL PHYSICAL EXAM BLOOD WORK UP INCLUDING ASSESSMENT OF IRON STORES, COELIAC PANEL, ELECTROLYTES, THYROID AND LIVER FUNCTION CONSIDER AXR TO ASSESS FOR CONSTIPATION CARBOHYDRATE BREATH TESTING LACTULOSE FRUCTOSE, LACTOSE SORBITOL, GLUCOSE CONSIDER UPPER AND LOWER GI ENDOSCOPY WITH SMALL BOWEL, COLONIC AND ILEAL BIOPSY CONSIDER BILIARY IMAGING AND CT ABDOMEN COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 52

How to interpret breath test results: Positive Test Interpretation of breath test results is based on measured hydrogen levels and described symptoms. A rise of hydrogen by 20 ppm has been shown in clinical trials to reflect a positive result (abnormal fermentation) and points to the potential value of limiting this carbohydrate from a patient s diet. Increasing levels of measured hydrogen usually correlate with reported symptoms. Referral to a dietician with expertise in dietary exclusions should be considered. Borderline Tests Borderline test results must be interpreted in the context of patient s clinical symptoms during the test. A rise of 20-25 ppm in the absence of any reported symptoms during the carbohydrate challenge indicates the patient is only mildly intolerant some restriction without strict lifelong avoidance of the identified carbohydrate may be appropriate in such cases. Low breath hydrogen levels in the setting of reported symptoms This group of patients may be methane producing and will have been identified by the initial lactulose test. Symptom evaluation is very important. The identification of significant symptoms during the analysis even with low hydrogen values suggests clinical management with appropriate dietary exclusion may be valuable. Low breath hydrogen levels with no symptoms Negative Test This group has no intolerance to the test carbohydrate. Early hydrogen peak with lactulose This test result may be explained by bacterial colonisation of the small bowel (SIBO) with early hydrogen release. A similar picture may result from rapid small bowel transit and lactulose delivery to the large intestine (with subsequent fermentation). Glucose testing could be considered as a confirmatory test in this cohort where clinical symptoms are relevant. Absence of hydrogen production with lactulose Non-production of hydrogen with a lactulose test suggests the patient is a predominant methane producer. Further testing can proceed with test sugars but symptom development will be the primary guide to test interpretation in such cases. COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 53

Typical results seen during Hydrogen breath testing LACTULOSE NEGATIVE (No hydrogen production, No symptoms) TIME (mins) 20 40 60 80 100 120 150 180 H2 (ppm) 4 4 4 4 4 4 4 4 SYMPTOM - - - - - - - - LACTULOSE POSITIVE (Suggestive of SIBO as hydrogen production and symptoms occur early) TIME (mins) 20 40 60 80 100 120 150 180 H2 (ppm) 4 24 56 39 19 16 11 8 SYMPTOM - - - - - LACTULOSE POSITIVE (Hydrogen positive, unlikely to be SIBO as hydrogen production occurs late) TIME (mins) 20 40 60 80 100 120 150 180 H2 (ppm) 4 6 6 9 24 36 30 16 SYMPTOM - - - - POSITIVE (Any carbohydrate test hydrogen production and symptoms) TIME (mins) 0 20 40 60 80 100 120 H2 (ppm) 6 12 15 25 40 37 57 SYMPTOMS - - - Bloating Bloating Bloating Bloating NEGATIVE (Any carbohydrate test No significant hydrogen production and No symptoms) TIME (mins) 0 20 40 60 80 100 120 H2 (ppm) 10 9 10 11 9 13 13 SYMPTOMS - - - - - - - BORDERLINE (Any carbohydrate test Low level of hydrogen production and symptoms) TIME (mins) 0 20 40 60 80 100 120 H2 (ppm) 10 9 10 14 28 27 13 SYMPTOMS - - Nauseous - COPYRIGHT 2014 MELBOURNE BREATH TEST PAGE 54