Implementation and interpretation of hydrogen …

1 IOP PUBLISHINGJOURNAL OFBREATHRESEARCHJ. Breath (2008) 046002 (9pp) and interpretation ofhydrogen breath testsAlexander Eisenmann1, Anton Amann2,4, Michael Said3, Bettina Datta1and Maximilian Ledochowski1,4,51 Department of Clinical Nutrition, Medical Hospital of Innsbruck, Austria2 Department of Anesthesia and General Intensive Care, Medical University of Innsbruck, Austria3 Department of Medicine, Military Hospital 2, Innsbruck, Austria4 Breath Research Unit of the Austrian Academy of Sciences, Dammstr 22, 6850 Dornbirn, 29 May 2008, in final form 2 July 2008 Published 24 July 2008 Online breath tests are non-invasive and safe diagnostic tools used to investigate functionalintestinal disorders. For the diagnosis of fructose or lactose malabsorption as well as for thedetection of small intestinal bacterial overgrowth syndrome, hydrogen breath tests are evenregarded as gold standard. However, standardization of the testing procedure and theinterpretation of the test results are still lacking.

2 In this paper, reliable information on theimplementation of the most common hydrogen breath tests and precise guidelines for theinterpretation of the test results are presented.(Some figures in this article are in colour only in the electronic version)1. IntroductionAt present, it is known that the exhaled breath of human beingscontains at least 2000 different substances and that, apart frombreathing, the lung s further essential function is the excretionof volatile substances [1 3]. hydrogen breath tests are basedon the physiological fact that healthy humans when fasting andat rest do not exhale hydrogen . As hydrogen is only generatedduring anaerobic metabolism and the human organism at restdoes not have anaerobic metabolism, the hydrogen excretedwith the exhaled air must originate from anaerobic bacteria[4]. The large bowel contains an enormous number of bacteriathat are predominantly anaerobes and produce a large quantityof hydrogen . It is assumed that the large intestine containsaround 1015bacteria whilst there is only a very small quantityof anaerobic bacteria in the small intestine [5].

3 Under normalconditions, the bacterial concentration in the small intestine isno higher than 102up to a maximum of 105. If the bacterialconcentration is above 105bacteria ml 1of the small intestinalcontent, a small intestinal bacterial overgrowth syndrome(SIBOS) exists [6 8]. Anaerobic bacteria prefer to metabolize5 Correspondence to: Dr Maximilian Ledochowski, Departmentof Clinical Nutrition, Medical University of Innsbruck, Innrain 66a, A-6020 Innsbruck, molecules, which, as part of a fermentation reaction,are initially broken down into short-chain fatty acids (SCFA),carbon dioxide (CO2) and hydrogen (H2), as illustrated large part of the CO2remains in the intestines andleads to the symptom of bloating. SCFA generate an osmoticgradient and, by doing so, absorb water into the intestinallumen, which leads to the symptom of diarrhea. The hydrogengenerated in the intestines passes the intestinal wall, ends up inthe bloodstream, is transported to the lungs and excreted as partof the exhaled breath.

4 There is strong evidence that the exhaledhydrogen indicates the quantity and the metabolic activity ofanaerobic bacteria in the intestines. Exhaled hydrogen canbe measured in parts per million (ppm) non-invasively andrelatively easily with hand-held breath test devices [9 11].The time at which the hydrogen concentration rises during abreath test gives an indication as to the part of the intestineswhere the fermentation takes place [12].2. SampleThis paper reflects our findings based on a total ofN=3374patients, who visited a doctor s office for internal medicine inInnsbruck, Austria, presenting functional intestinal +09$ 2008 IOP Publishing Ltd Printed in the UKJ. Breath (2008) 046002A Eisenmannet alFigure reaction of sugar molecules (lactose) in theintestines as found in lactose data were collected from January 1997 to April mean age of our patients was years (range ), including (n=1064) male and (n=2310) female subjects. We carried out 1783 fructose, 1590lactose, 271 lactulose, 200 sorbitol, 14 xylose and 9 xylitolload tests on our patients.

5 The investigation conforms withthe principles outlined in the Declaration of Helsinki, andinformed written consent was obtained from each participantto be included in this Preparation for the testPrior to the test, the patient should fast for at least 12 h. Duringthis time, he must not drink anything apart from water. Inparticular, he must be advised to avoid milk and/or fruit juiceson the day prior to the test. The last meal on the day precedingthe test should not be too ample and should ideally not consistof any fiber. On the day prior to the test, products such asonions, leeks, garlic, cabbage, pickled cabbage or beans shouldbe avoided. Twelve hours prior to the test, the patient shouldstop smoking and chewing gum [13]. If, due to an oversight,the patient does smoke, it is still possible to conduct the testat a low basal H2value (<5 ppm). If, repeatedly, increasedbasal H2values are measured in a patient, it is recommendedto measure the exhaled content of carbon monoxide (CO) toestablish whether the patient did smoke shortly before the from vitamins, laxatives and antibiotics, medicinescan be taken with pure water on the day of the of dentures must not use an adhesive on the day ofthe test.

6 The claim that it is contraindicated to brush theteeth prior to the breath test because most types of toothpastecontain sorbitol or xylitol is incorrect. In our sample we havenever encountered problems due to patients brushing teethin the morning. In contrast, when patients fail to brush theirteeth, increased basal H2concentrations may occur and evendistort the test result. Besides, carrying out the test on patientswho did not brush their teeth beforehand is unpleasant for thepatient and the staff What must be done prior to starting the breath test?First of all, it is most important to establish that there are nocontraindications against the breath test. This applies above allto children with suspected hereditary fructose intolerance. InTable for hydrogen breath contraindications Known or suspected hereditary fructoseintolerance (CI for fructose load test, sorbitol load test) Known or suspected (postprandial) hypoglycaemiaRelative contraindications Administration of antibiotics (in the last four weeks) Colonoscopy (in the last four weeks) Irrigoscopy (in the last four weeks) Fluoroscopy of the small bowelaccording to Sellink (in the last four weeks) Ileostomy (except for the diagnosis of SIBOS)the case of hereditary fructose intolerance (HFI), a fructoseload is strictly contraindicated as it could generate severehypoglycaemia.

7 As the clinical symptoms of HFI and fructosemalabsorption can be very similar, particular care needs tobe taken with regard to children. In such cases, a moleculargenetic test to establish HFI should always be carried out priorto a fructose load test. In very rare cases, mainly in compoundheterozygotic cases where the clinical course of the conditionis not quite severe, it is possible that HFI is not diagnosed untiladulthood [14].Additionally the patient s current and most recentmedication needs to be documented. Antibiotics continueto distort the test result of the hydrogen breath test to up tofour weeks after they have been discontinued [15]. Therefore,it is recommended not to carry out the test if this has been thecase. Equally, the taking of laxatives, in particular of lactulose(LaevolacR ) should be discontinued at least three days priorto the test. After a colonoscopy the intestinal flora needs upto four weeks to recover. Therefore, hydrogen breath testsshould not be carried out before this time has passed.

8 In anycase, after a colonoscopy, one has to wait until the patient hashad at least three normal bowel movements. The same appliesafter the execution of other intestinal examinations where prior bowel cleaning has been carried out, such as, for example,after an irrigoscopy, a Sellink procedure or other bowel tests [16]. A list of contraindications for hydrogen breath tests isfeatured in Emergency medicationWhilst emergencies associated with breath tests tend to berare, it is still important to be prepared for all complaints occur, they tend to be migraine attacks,headaches or stomach cramps. However, in rare cases,patients may experience panic attacks, dizziness, allergy-like reactions or tachyarrhythmias. Appropriate emergencymedications should be stocked by a breath test laboratory(antihistamines, cortisone, migraine drugs, spasmolytics,paracetamol etc). Fasting stateThe fasting state has to be validated. This is usually done bya basal H2measurement.

9 The basal H2level should be below10 ppm (better<5 ppm). If the basal H2is 10 ppm or above, the2J. Breath (2008) 046002A Eisenmannet alSymptoms during FTT (N=1790) paindiarrhoedizinessindigestionmiscellan eousbelchingchillheartbrunno symptomsFigure of symptoms during fructose tolerance test (N=1790).breath test cannot be used. In such a case, the patient shouldbe asked to return on another day and to fast for at least 16 hbefore undergoing the breath test again. Beside fibre the lastmeal prior to the test should not contain milk (dairy products)either, if lactose intolerance is suspected. If potential fructoseintolerance is suspected, the last meal should additionally bedevoid of fruit. Furthermore, it is advisable that, on themorning of the day when the test is carried out, the patientdrinks a glass of hot water. This assists the peristalsis andproduces a wash out of the bowel bacteria, which contributeto the production of fasting breath DocumentationThe production of comparable and reliable results ofhydrogen breath tests does not just require a standardizedimplementation of the breath test but also exact from measured H2levels, it is above all necessary toestablish the symptoms that existed each time a measurementis taken.

10 The establishment of symptoms is essential for theinterpretation of the test results and is of major importancefor the clinical consequences. The symptoms that may occurduring a test are not at all limited to gastrointestinal symptomssuch as bloating, hyperperistalsis, diarrhea or abdominal , the patient experiences extra-intestinal symptomssuch as fatigue, dizziness, headache or heartburn (seefigure2).4. Implementation of hydrogen breath testsEach breath test starts with an initial measurement in thefasting state (basal value) prior to the patient having beenadministered a test substance. The procedure of exhalingshould be carried out according to the instructions of themanufacturer of the breath test device. As hydrogen isdistributed differently depending on the body position, thepatient must adopt the same position as during the basalmeasurement [17]. When outpatient, non-bedridden patientsare tested, we recommend to conduct measuring on a sittingsubject.