Application of the breath hydrogen test in gastroenterology]

The diagnostic capacities of the breath hydrogen test in gastroenterology are discussed in the article. The authors describe the results of their own research--determination of the intestinal bacterial contamination in patients with chronic biliary pancreatitis with the help of the Micro H2 breath hydrogen analyzer.     

Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation

BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.     

Lactulose hydrogen breath test in orocecal transit assessment

Orocecal transit time can be studied easily using the hydrogen breath test with lactulose, but the method has some important limitations. The orocecal transit time of 10 patients suffering from irritable bowel syndrome was measured twice, at a one-week interval, by breath test and scintigraphy simultaneously using an aqueous solution of 20 g lactulose containing 74 MBq of [^99mTc]DTPA. Abdominal radioactivity and alveolar hydrogen values obtained every 5 min were noted and used to obtain the following: orocecal transit time by the two methods; ileocecal lactulose flow; total and per gram of lactulose hydrogen production; mean hydrogen concentration during the right colon filling; and measurement error of the breath test with respect to the scintigraphy. In the case of the breath test, the orocecal transit time intrapatient reproducibility was better (coefficient of variation =13.5%) when a hydrogen threshold increment of 5 ppm was used; the best correlation with the scintigraphic measurement was observed at this threshold (r=0.90,P<0.001). The breath test overestimated orocecal transit time with the error correlating negatively and significantly with the total hydrogen production and, particularly, the mean hydrogen concentration (r=0.79,P<0.01): for a mean hydrogen concentration of more than 15 ppm, the error was negligible, while within this value there was a noticeable overestimation. To conclude, the lactulose hydrogen breath test is capable of giving an accurate measurement of orocecal transit time if a hydrogen threshold increment of 5 ppm is chosen and if the mean hydrogen concentration in the first 30 min of the right colon filling is taken into account.     

Acidic colonic microclimate--possible reason for false negative hydrogen breath tests.

About 5% of normal subjects fail to produce increased hydrogen breath concentration after ingestion of the non-digestible carbohydrate lactulose (low hydrogen producers). The existence of low hydrogen producers limits the diagnostic use of hydrogen (H2) breath tests. We studied the effects of lactulose and of magnesium sulphate (MgSO4) pretreatment on stool-pH and on hydrogen exhalation after oral loading with lactulose or lactose in 17 hydrogen producers and 12 low hydrogen producers. In seven hydrogen producers acidification of stool pH by lactulose pretreatment (20 g tid) decreased hydrogen exhalation and three of seven (43%) became low hydrogen producers. In contrast, after pretreatment of eight low hydrogen producers with magnesium sulphate (5 g twice daily) all eight produced hydrogen after a lactulose load. Similarly four lactose intolerant low hydrogen producers had abnormal lactose hydrogen breath tests after MgSO4 pretreatment. MgSO4 pretreatment neither resulted in false positive lactose hydrogen breath tests in five lactose tolerant hydrogen producers, nor increased the hydrogen exhalation in five additional hydrogen producing controls after ingestion of lactulose. The results of these studies confirm that hydrogen production from lactulose decreases when the colonic pH is lower (lactulose pretreatment), and increases when colonic pH is higher (MgSO4 pretreatment). In low hydrogen producers the lacking increase of H2 exhalation after ingestion of non-digestible carbohydrates can be overcome by MgSO4 pretreatment, thus increasing the sensitivity of the test by avoiding false negative hydrogen breath tests in low hydrogen producers with disaccharide malabsorption or maldigestion. The underlying mechanism of this remarkable effect of MgSO4 pretreatment warrants further investigation.     

The effect of gastric secretion on orocoecal transit time measured with the hydrogen (H2) breath test

Orocoecal transit time was studied by means of a hydrogen (H2) breath test after a standard meal in patients with peptic disease before and during treatment with ranitidine, in patients with gastric achlorhydria, and in healthy acid-secreting volunteers. Treatment with ranitidine prolonged the orocoecal transit time in patients with peptic disease from 201.9 +/- 18.3 (SEM) to 242.3 +/- 18.3 min (p less than 0.05). Also in patients with achlorhydria, the orocoecal transit time was prolonged (276.2 +/- 20.3 min), compared to the control group of healthy acid-secreting volunteers (213.5 +/- 15.7 min), (p less than 0.05). The orocoecal transit time did not correlate with gastric bacterial concentrations in the groups investigated, nor with the subjects' age. It was not correlated to the pH in the gastric juice of acid-secreting individuals, either with or without treatment. As gastric emptying was not evaluated in this study, it is impossible to state whether gastric stasis or inhibited small bowel motility, or both, cause the delayed transit in achlorhydria and during treatment with ranitidine. We suggest that the reduction of gastric juice volume could be the cause.     

乳果糖氢呼吸试验测定口-盲肠传递时间

目的测定功能性消化不良（ＦＤ）和肠易激综合征（ＩＢＳ）患者口－盲肠传递时间（ＯＣＴＴ）．方法应用乳果糖氢呼吸试验（ＬＨＢＴ）测定了正常人１３例，ＦＤ２０例和ＩＢＳ（其中１５例主诉腹泻，１６例主诉便秘）３１例患者的ＯＣＴＴ．结果正常人ＯＣＴＴ为９５４±１９６ｍｉｎ，ＦＤ患者（９９２±２４５ｍｉｎ）与正常人比较无显著性差异（Ｐ＞００５），但其中５例动力障碍型ＦＤ的ＯＣＴＴ则显著延长（１２９０±１２０ｍｉｎ，Ｐ＜００１），以便秘为主的ＩＢＳ患者ＯＣＴＴ显著延长（１５４４±５５７ｍｉｎ，Ｐ＜００１），以腹泻为主的ＩＢＳ患者ＯＣＴＴ显著缩短（７３１±２２２ｍｉｎ，Ｐ＜００５）．结论ＦＤ和ＩＢＳ患者存在小肠动力学异常，ＬＨＢＴ可作为辅助检查小肠动力学异常的手段之一．     

Hydrogen breath test as an indicator of the quality of colonic preparation for colonoscopy

BACKGROUND: Breath hydrogen levels after ingestion of polyethylene glycol were evaluated as a method of predicting the quality of colonic preparation. METHODS: One hundred patients undergoing nonemergency colonoscopy were recruited for this study. After fasting overnight, they were instructed to ingest a polyethylene glycol solution containing 12 g lactulose at a rate of 50 mL every 5 minutes for 2 hours. During ingestion of the polyethylene glycol solution, breath samples were taken at 15-minute intervals for 240 minutes and breath hydrogen concentration was measured. RESULTS: The preparation for colonoscopy was judged to be poor in 18% and adequate in 82%. The breath hydrogen levels over 90 minutes were significantly higher in the poor group than in the adequate group. In all patients with a breath hydrogen level less than 10 parts per million at 240 minutes, the preparation was adequate. Conversely, all patients with a poor preparation had a breath hydrogen level of more than 10 ppm at 240 minutes. CONCLUSIONS: The hydrogen breath test effectively predicts adequacy of colonic preparation.     

Evaluation of the hydrogen breath test in man: definition and elimination of the early hydrogen peak.

After ingestion of a non-absorbable carbohydrate breath hydrogen excretion increases early at about 10 minutes, and again later when the ingested carbohydrate enters the caecum. The late rise has been used as a marker of mouth to caecum transit time, but the source of the early rise has not been satisfactorily explained. We studied in 60 healthy volunteers the source and frequency of the early rise in breath hydrogen after ingestion of a non-absorbable carbohydrate. After ingestion of either lactulose solution (10 g in 150 ml water), lentil soup (46 g carbohydrate) or solid meal containing baked beans (15 g carbohydrate), breath hydrogen was significantly raised above basal concentrations within 10 minutes (81 +/- 27, 395 +/- 138 and 110 +/- 52% above basal respectively). A significant rise in breath hydrogen (75 +/- 21%) occurred 10 minutes after sham lactulose feeding (lactulose applied to oral cavity but not swallowed), but no early peak occurred after sham saccharin feeding (non-fermentable carbohydrate), intragastric or intraduodenal administration of lactulose. Ten of the 12 subjects given lactulose sham feeding were restudied after oral hygiene with chlorhexidine mouthwash. In these the early hydrogen peak was abolished. Oral hygiene also reduced the occurrence and magnitude of the early hydrogen rise after lactulose ingestion. These findings indicate that the early rise in breath hydrogen observed after ingestion of lactulose is produced by interaction with oral bacteria.     

Evaluation of the rice breath hydrogen test for small intestinal bacterial overgrowth

OBJECTIVES: The aims of this study were 1) to document the sensitivity, specificity, and predictive values of the rice breath hydrogen test for small intestinal bacterial overgrowth; 2) to determine the possible influence of concurrent gastric bacterial overgrowth and gastroduodenal pH on the efficacy of this test; and 3) to investigate whether reliability is limited by an inability of small intestinal luminal flora to ferment rice or its product of hydrolysis, maltose. METHODS: Twenty adult subjects were investigated with microbiological culture of proximal small intestinal aspirate and a 3-g/kg rice breath hydrogen test. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of small intestinal luminal flora to ferment rice and maltose, its product of hydrolysis, were determined. RESULTS: Sensitivity of the rice breath hydrogen test for small intestinal bacterial overgrowth was 33% and remained low even when subjects with small intestinal overgrowth with oropharyngeal-type (38%) and colonic-type flora (20%) and those with concurrent small intestinal and gastric bacterial overgrowth (40%) were considered separately. Sensitivity remained suboptimal despite favorable gastroduodenal luminal pH and documented ability of bacterial isolates to ferment rice and maltose in vitro. Specificity of the rice breath hydrogen test for small intestinal bacterial overgrowth was 91%. Positive predictive value, negative predictive value, and predictive accuracy were 75%, 63%, and 65%, respectively. CONCLUSIONS: Clinical value of the rice breath hydrogen test for detecting small intestinal bacterial overgrowth is limited. The rice breath hydrogen test is not a suitable alternative to small intestinal intubation and culture of secretions for the detection of small intestinal bacterial overgrowth.     

Comparison of bentiromide test and rice flour breath hydrogen test in the detection of exocrine pancreatic insufficiency

Bentiromide test (BT) has been recently approved in the United States for screening patients with chronic pancreatitis for exocrine insufficiency. A few reports have suggested that the rice flour breath hydrogen test (RFBHT)--i.e., breath hydrogen analysis after rice flour ingestion--may also be useful in diagnosing exocrine pancreatic insufficiency. We conducted this study to compare the diagnostic value of these two tests in chronic alcoholic (n = 14) and nutritional or tropical (n = 6) pancreatitis. False-positive results were not noted with either of these two tests in 12 healthy volunteers. BT was positive in 28.6% of patients with chronic alcoholic pancreatitis and in 16.7% of patients with tropical pancreatitis. In comparison, RFBHT was almost twice as sensitive as BT in detecting insufficiency in patients with alcoholic pancreatitis (50 vs. 28.6%) and four times as sensitive in patients with tropical pancreatitis (66.7 vs. 16.7%). Only one patient in our study had a positive BT but a negative RFBHT. We recommend RFBHT as a simple, safe, and inexpensive test in screening patients for exocrine pancreatic insufficiency.     

Applicability of short hydrogen breath test for screening of lactose malabsorption

The gold standard for diagnosing lactose malabsorption is the H₂ hydrogen breath test (HBT). Different methods of HBT have been proposed. However, in clinical practice the HBT is often shortened to 1–2 hr without proper validation. Our objective was to establish whether the usefulness of the HBT is influenced by shortening of the test and/or by substrate variations. In 62 patients with clinically suspected lactose intolerance and a positive lactose HBT we calculated the sensitivity of the HBT depending on the duration of the HBT. To determine whether substrate variations influence the sensitivity of the HBT, in another group of 32 patients with clinically suspected lactose intolerance and a positive milk HBT, the sensitivity of the HBT was also calculated depending on the duration of the test after milk ingestion. In other unselected 97 individuals, the result of the HBT with 360 ml of whole milk supplemented with lactose was compared with a symptomatic score for lactose intolerance to evaluate the specificity of the shortened milk HBT. Breath H₂ excretion was significantly higher after lactose than after milk load (P < 0.01), and the increase in H₂ appeared earlier with lactose than with milk (60 vs 90, min respectively). HBT duration influenced the sensitivity of the test that decreased from 95% for the 3-hr HBT to 37% for the 1-hr HBT with lactose and from 80% for 3-hr HBT to 21% for 1-hr HBT with milk. The specificity was similar for the 3-hr milk HBT and the 5-hr test (67 vs 62%). In conclusion, for screening of lactose malabsorption, the HBT can be shortened to 3 hr without loss of sensitivity and specificity, when a high dose of lactose load is used.     

Comparison of the 1-gram (14)C-D-xylose breath test and the 50-gram hydrogen glucose breath test for diagnosis of small intestinal bacterial overgrowth

BACKGROUND/AIMS: Culture of small bowel aspirate is the most direct method and the gold standard for diagnosing small intestinal bacterial overgrowth. However, cultures are cumbersome and fluoroscopy is required for obtaining aspirate. Therefore, different breath tests such as the xylose breath test and the hydrogen breath test have been developed. There is no general agreement as to which test is to be preferred. In the only previous direct comparison between these two tests an advantage for the 1-gram-(14)C-D-xylose breath test was found. The aim of the study was to compare the 50-gram glucose hydrogen breath test and the 1-gram (14)C-D-xylose breath test in relation to results of cultures of small bowel aspirate. METHODS: Forty-six consecutive patients, mean age 57 (range 27-87) years, 12 men and 34 women, were included because of suspicion of small intestinal bacterial overgrowth. After small bowel aspiration, all patients received a solution of 1 g xylose, labelled with 50 microg (14)C-D-xylose, and 50 g glucose dissolved in 250 ml water. The concentration of breath hydrogen was analyzed every 15 min for 2 h and (14)CO(2) was analyzed every 30 min for 4 h. A positive hydrogen breath test was defined as a rise in hydrogen concentration of 15 ppm. A positive xylose test was defined as an accumulated dose 4.5% after 4 h. Two definitions for a positive culture were used, either growth of 10(5 )colonic-type bacteria/ml or growth of 10(5) bacteria/ml of any type. RESULTS: Twenty-four patients had growth of 10(5) bacteria, of whom 10 had growth of 10(5) colonic-type bacteria in small bowel aspirate. Twenty-two patients had no significant growth. The hydrogen breath test and the xylose breath test had a sensitivity for growth of 10(5) bacteria of 58 and 42%, respectively. For growth of 10(5 )colonic-type bacteria the sensitivity was 90% for the hydrogen breath test and 70% for the xylose breath test. The specificity was similar for the two tests. CONCLUSION: Although no significant difference between the two tests was found, there was a tendency in favor of the 50-gram glucose hydrogen breath test. The simplicity in combination with high sensitivity makes the hydrogen breath test suitable as a screening method to select patients for further investigation.     

Methodological aspects of the use of the hydrogen (H2) breath test

Normalization of the breath hydrogen (H2) concentration by simultaneous determination of breath carbon dioxide (CO2) and the addition of lactulose to a liquid meal have been recommended to improve the reproducibility of the hydrogen breath test. To assess the clinical relevance of these recommendations, we studied 64 children of 4 different age groups and 12 adults. Simultaneous determination of CO2 concentration and normalization of breath H2 resulted in a marked decrease of intestinal transit time and its variation in children; in adults, however, this correction was negligible. With lactulose alone, the mean coefficient of variation within individuals was only 11.7% and 13.2%, with and without H2 normalization, respectively. Therefore, the addition of a liquid meal does not seem to be necessary.     

The lactulose hydrogen breath test as a diagnostic test for small-bowel bacterial overgrowth.

The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacterial overgrowth using the 14C-glycocholate breath test for comparison. Twenty-seven patients with suspected bacterial overgrowth and 37 control patients were studied. The lactulose test was positive in 8 out of 9 patients with Subsequently proven bacterial overgrowth, all of whom had positive 14C-glycocholate tests. However, 6 patients with ileal disease or resection had positive 14C-glycocholate tests but negative lactulose tests. subsequent bacteriological study of duodenal juice from these patients was negative. Negative results were obtained by both tests in the remaining 12 patients, none of whom were subsequently shown to have bacterial overgrowth. All 37 control subjects had negative lactulose tests. The lactulose breath test is a simple and promising diagnostic test for the detection of small-bowel bacterial overgrowth and, unlike the 14C-glycocholate test, has the advantage of being able to distinguish bacterial overgrowth from ileal disease.     

Reproducible lactulose hydrogen breath test as a measure of mouth-to-cecum transit time

Breath hydrogen monitoring after oral lactulose syrup is a conventional measure of mouth-to-cecum transit time (MCTT), but its reproducibility has been questioned. We compared the reproducibility of five measurements of MCTT after a conventional breakfast (380 kcal) taken with tea containing 20 g lactulose to five measurements of MCTT after 20 g lactulose in water in eight normal volunteers. Individual mean breakfast transit time was not significantly different from lactulose transit time in each of the seven subjects, but one had a breakfast transit time of 151±15 min and a lactulose transit time of 86±22 minutes (¯X ±sd, P<0.001). The coefficient of variation of breakfast transit time (11.6±5.3%, range: 6.9–24.2%) was less than that of lactulose transit time (30.7±7.8%, range: 22.1–50.0%, P<0.001). In a second set of experiments, the liquid phase marker ( ^99m Technetiumdiethylene triamine pentaacetic acid) emptied from the stomach more rapidly after the lactulose solution (T1/2 16.3±5.4) than after the breakfast (33.9±10.9 min, P<0.01) and MCTT was shorter after lactulose (77±32 vs 104±40 min, trespectively, P<0.05). There was no correlation between MCTT of lactulose and breakfast and between half-time gastric emptying and MCTT of either lactulose or breakfast. We conclude that the ingestion of inert lactulose induces an abnormally rapid MCTT and that breakfast MCTT is a much more reproducible investigation and should be employed in studies requiring serial measurements.     

山梨醇氢呼气试验测定口─盲肠通过时间及西沙比利对其影响的研究

目的对山梨醇氢呼气试验测定口─盲肠通过时间进行方法学研究，并观察西沙比利对健康人及患者口─盲肠通过时间的影响。方法以不同剂量的山梨醇作为试验糖并与泛影葡胺放射学方法进行对照。结果１５ｇ山梨醇的产氢率较高，副作用较少。山梨醇呼气氢试验测得的口─盲肠通过时间与泛影葡胺放射学方法的结果之间有显著的相关性（ｒ＝０．９１９）。十二指肠球部溃疡、慢性胃窦炎、肝硬化及糖尿病患者口─盲肠通过时间与正常对照组比较，差异有非常显著性（Ｐ均＜０．００１），服用西沙比利（１０ｍｇ，三次／日×３天），正常对照者、十二指肠球部溃疡、肝硬化及糖尿病患者口─盲肠通过时间显著缩短（Ｐ均＜０．００１）。结论（１）山梨醇呼气氢试验是简易、可靠、重复性好及非创伤性的测定口─盲肠通过时间的方法；（２）西沙比利可以显著缩短十二指肠球部溃疡、肝硬化及糖尿病患者的口─盲肠通过时间，其作用可能与加速胃排空，缩短小肠通过时间有关。