Limitations of the triolein breath test.

Patients being investigated for intestinal absorptive capacity were classified as normals or malabsorbers on the basis of three fat absorption tests. Malabsorbers were further classified as mild, moderate, severe or gross according to severity of malabsorption. Using this classification system the triolein breath test was evaluated in 53 patients. Seventeen patients were excluded because their graph of percentage breath [14C]carbon dioxide versus time was exponential indicating that the peak [14C]-carbon dioxide may be occurring later than the six hour duration of the test. The sensitivity and specificity of the triolein breath test were found to be 100% and 96%, respectively and moderate correlations with the individual fat absorption tests were found. However, the breath test was limited in its capacity to predict the severity of malabsorption. Carbon dioxide output was also measured in order to determine the applicability of using an assumed value. The respiratory quotient and variability of results were high in nineteen patients indicating possible hyperventilation. In 32 patients with reproducible results and normal respiratory quotients the average carbon dioxide output was 8.66 mmol/kg per hour with a wide range of 5-12.4 mmol/kg per hour. Consequently the use of an assumed carbon dioxide output can introduce considerable errors in the triolein breath test. This study highlights drawbacks of the triolein breath test, particularly problems in using an assumed carbon dioxide output for its calculation, its inability to predict the severity of malabsorption and the nature of the dietary load used.     

Jejunal mucosal architecture and fat absorption in male homosexuals infected with human immunodeficiency virus

Diarrhoea and weight loss are common features of human immunodeficiency virus (HIV) disease. The mechanism of diarrhoea occurring in the absence of known enteropathogens is currently unknown. We have measured fat absorption, using the 14C triolein breath test, and quantitatively assessed jejunal villous architecture in 20 male homosexuals at various clinical stages of HIV disease. Enteropathogens were not detected in any subject at the time of jejunal biopsy in stool or jejunal mucosa. Partial villous atrophy was the sole histological abnormality and was detected at any clinical stage of HIV disease. The 14C triolein breath test quantitatively correlated with the degree of jejunal villous atrophy. In addition subjective presence of diarrhoea was related to the detection of fat malabsorption. Thus diarrhoeal disease in HIV infected patients in the absence of enteropathogens may be due to jejunal enteropathy and may be present at early clinical stages of HIV disease.     

Breath tests in the diagnosis of small intestine bacterial overgrowth

Analysis of breath specimens for volatile metabolites of orally administered substrates offers a simplified detection method for the presence of an abnormal small-intestinal flora. This technique is not only simpler and more acceptable to patients than jejunal aspiration, but also gives quicker information to the clinician than microbiologic culture of the jejunal aspirate. Experience with a probe which is usually completely absorbed before the colon is reached (1 g 14C-xylose) has demonstrated better test sensitivity (separating normal from abnormal) and test specificity (separating bacterial overgrowth from small-bowel malabsorption) than that seen with a probe which normally has substantial passage of substrate to the colonic bacteria (as seen with the 14C-bile acid breath test). Ongoing evaluation of nonradioactive probes (H2 generation from fermentable carbohydrate, 13CO2 generation from 13C-labeled substrate similar to the principle of the 14C-xylose breath test) offers promise for use of bacterial overgrowth breath tests in children and reproductive-age females.     

A new method for the detection of hydrogen in breath and its application to acquired and inborn sugar malabsorption

An electrochemical device for the measurement of hydrogen in end-expired air is described and compared with an existing gas Chromatographie method. The application of both these methods to subjects with acquired and inborn defects of sugar malabsorption is documented. Our simplified method of breath collection and the rapid estimation of hydrogen concentration provides a reliable, convenient and well-tolerated means of detecting sugar malabsorption.     

Comparison of the proportion of unconjugated to total serum cholic acid and the [14C]-xylose breath test in patients with suspected small intestinal bacterial overgrowth.

The proportion of unconjugated to total cholic acid in fasting serum and the 1-gram [14C]-xylose breath test were determined in 36 patients with suspected bacterial overgrowth of the small intestine. Twenty-two patients had an abnormal [14C]-xylose breath test, indicating bacterial overgrowth. The proportion of unconjugated to total cholic acid was significantly higher in the patients with an abnormal breath test compared with those displaying a normal breath test (47 +/- 5% vs 16 +/- 3%). A good correlation was obtained between the proportion of unconjugated to total cholic acid and the breath test (r = 0.63, n = 36). Provided the [14C]-xylose breath test is reliable as a test of bacterial overgrowth, determination of the proportion of unconjugated to total cholic acid in fasting serum had a sensitivity of 73% and a specificity of 94%. It is suggested that determination of the proportion of unconjugated to total cholic acid in peripheral venous blood may be useful as a simple screening test for detection of bacterial contamination of the upper small intestine provided the patients do not have bile acid malabsorption.     

The fat meal test of malabsorption: some further experience

A fat meal test was evaluated in 21 healthy controls, 14 pathological controls and 11 malabsorption patients. The amount of fat used was 1 g per kg body wt, and the time for the post-cibal blood sampling was 2 h after the start of the meal. Combining serum triglyceride determination and serum turbidity measurement, the malabsorption group was fully discriminated from the control groups.     

The [14C]-triolein breath test is not valid as a test of fat absorption.

The [14C]-triolein breath test is used as a test of fat absorption. However, its validity has not been established. The aim of this study was to investigate, whether the absorption of [14C]-triolein could be estimated from the breath test, and whether the breath test could be useful as a clinical test. The [14C]-triolein absorption was estimated from faecal measurements, using 51CrCl3 as non-absorbable marker. The breath test was done according to the standard technique with hourly estimations of the 14CO2 expiration. Fifty-one patients participated. A nearly perpendicular, curvilinear relation between the 6-h cumulative 14CO2 expiration and the [14C]-triolein absorption was found, and no obvious cut-off level for normal 14CO2 expiration could be identified. Accordingly, the diagnostic sensitivity of the breath test was 80% at the expense of a specificity of 45%. In 19 patients duplicate measurements were done. A high intra- and inter-individual variation in the fraction of absorbed [14C]-triolein, expired within 6 h, was found. It is concluded that expiration of 14CO2 is influenced by factors other than the absorption of [14C]-triolein, and that the [14C]-triolein breath test is not useful as test of fat absorption.     

Methodological aspects of breath hydrogen (H2) analysis. Evaluation of a H2 monitor and interpretation of the breath H2 test

The reliability of end-expiratory hydrogen (H2) breath tests were assessed and the significance of some important pitfalls were studied, using a compact, rapid H2-monitor with electrochemical cells. The H2 response was shown to be linear and stable. The reproducibility of the breath collection technique was determined in 20 patients following ingestion of lactulose. The increment between consecutive means of duplicate samples indicative of a significant rise of H2 concentration never exceeded 10 p.p.m., the mean coefficient of variation of the duplicate samples was below 5%. Fasting H2 levels were studied in 10 healthy adults during a 4-month period and they showed very marked inter- and intra-individual variability (16% above 40 p.p.m.). Initial peaks (early, short-lived H2 rises unrelated to carbohydrate malabsorption) were identified in 25% of the breath tests (in 4% above 20 p.p.m). It is concluded that the technique used for interval sampling of end-expiratory breath samples for H2 concentration gives reliable results. The biological significance of H2 concentration increments can only be evaluated if the limitations of the technical procedures and the individual ability to produce H2 is known.     

Hydrogen breath test in the diagnosis of lactose malabsorption: accuracy of new versus conventional criteria

Increased hydrogen excretion in the breath after carbohydrate ingestion, an expression of carbohydrate malabsorption, represents the pathophysiologic basis of the hydrogen breath test, a simple, noninvasive, reproducible test for the diagnosis of this condition. Few data are available concerning the breath hydrogen response that most accurately identifies carbohydrate malabsorption. In this article we report our application for the first time in clinical practice of 2 recently described, more accurate criteria for the diagnosis of lactose malabsorption (ie, breath hydrogen excretion value > 6 parts per million (ppm) 6 hours after carbohydrate load and a sum greater than 15 ppm for the breath hydrogen values obtained 5, 6, and 7 hours after carbohydrate load). On 3 separate days, we subjected 84 consecutive patients with functional or organic gastrointestinal disease to measurement of hydrogen excretion in the breath after the administration of lactose to test for lactose malabsorption; after the administration of lactulose as a means of ruling out false-negative results resulting from hydrogen-nonproducer status; and after the administration of a nonabsorbable electrolyte solution as a means of ruling out false-positive results caused by the mixing of intestinal content and release of preformed hydrogen trapped in the feces. According to the conventional criterion, 51% of the subjects proved to be lactose malabsorbers. Positive results were obtained with the use of the 6th-hour criterion in 76% of patients, and positive results were found in 80% when the sum of the excretion at hours 5, 6, and 7 was used as the criterion (P < .05 for both comparisons). Ten of 21 and 11 of 25, respectively, showed intolerance symptoms. It was therefore possible for us to diagnose lactose malabsorption in 24% and 27% of patients, respectively, who tested negative according to the conventional criterion. The conventional criterion must be abandoned and these new criteria adopted.     

The daytime breath hydrogen profile: technical aspects and normal pattern

A method is described for breath sampling which can be used for breath hydrogen estimations not only in clinical practice, but also at home. Sampling of end-expiratory air is performed using a 10-ml syringe with a side hole. The samples are transferred to 3-ml vacuum tubes, which can be stored and mailed without significant loss of hydrogen. The hydrogen concentration is estimated gas chromatographically using 0.4 ml of sampled air. This method was used to assess the breath hydrogen pattern under normal circumstances: the daytime breath hydrogen profile. Fourteen children sampled their breath at 30-min intervals during one full day, and recorded diet and activity. The normal daytime breath hydrogen profile showed a typical pattern. Morning values were low, but the evening values were markedly increased in half of the children. These patterns differed markedly from those registered in three children with carbohydrate malabsorption. The daytime breath hydrogen profile, which is easy to perform and applicable at home, might provide valuable additional information in the investigation of children with suspected carbohydrate malabsorption.     

Molecularly-defined lactose malabsorption, milk consumption and anthropometric differences in adult males

BACKGROUND: Lactose malabsorption (LM) may be associated with reduced skeletal calcium content. Diagnosis to date has been based on indirect methods, with a high false-negative rate. Identification of the LCT polymorphism led to development of a PCR-based test. AIM: To evaluate the PCR-based test compared to a combination the hydrogen breath test and the lactose tolerance test, and investigate anthropometrical differences, changes in bone mineral density and oral calcium intake according to LCT polymorphism and milk-drinking habits. METHODS: All participants (n = 278) underwent clinical examination, with measurement of height, weight and bone density (DXA), and were genotyped for LCT polymorphism (LCT CC or LCT TT: CC is associated with LM). A subgroup (n = 51) had a hydrogen breath test and a lactose tolerance test, in addition to genotyping. RESULTS: Detection of LM by LCT polymorphism was highly significant (p = 0.001). The correlation between LCT genotype and self-reported milk-intolerance or dislike of milk with was slight, but the correlation with functional tests was highly significant. Non-milk-drinkers were lighter (-5 kg) and significantly shorter (-4 cm) than milk-drinkers (p = 0.07 and 0.04, respectively). Total calcium consumption was lower among non-milk-drinkers by about 18% (p = 0.03). DISCUSSION: Genotyping is an economic, quick and convenient method for diagnosing lactose malabsorption, with results comparable to existing tests. Sufficient calcium consumption may be relevant to body growth, as milk-drinkers were taller. Negative calcium bone balance may be prevented when provision is made for adequate calcium intake.     

Effects of apolipoproteins on lipoprotein lipase activity of human adipose tissue.

The effect of apolipoproteins isolated from HDL and VLDL on the activity of lipoprotein lipase (LPL) of adipose tissue was studied. The CII apoprotein was found to activate LPL. This activation was strongly inhibited by CI, AI (apo-Lp-Gln I), and the arginine-rich apoprotein, whereas AII and CIII exhibited a considerably lower inhibitor effect.     

Improved gas chromatographic quantitation of breath hydrogen by normalization to respiratory carbon dioxide.

A gas-solid chromatographic system using tandem silica gel and molecular sieve columns is described for the measurement of hydrogen, carbon dioxide, oxygen, and nitrogen in samples of respiratory gases. This system has a detection limit of 2 ppm of hydrogen in a 1 ml sample and can measure 120 ppm H2 and 5% CO2 with relative standard deviations of 1.3% and 1.7%, respectively. Improved sample storage and withdrawal techniques are described that give reproducible values for up to 6 weeks after collection. Finally we show that normalization of breath hydrogen values to an alveolar concentration, using the observed carbon dioxide concentrations, substantially reduces the range and variance of apparent H2 concentrations in human subjects. Normalization eliminates the need for rebreathing or end-expiratory collection techniques and substantially increases the reliability and clinical utility of hydrogen breath measurements in noninvasive tests of carbohydrate malabsorption.     

Regulation of plasma plant sterol levels in patients with gut resections

The role of cholesterol and bile acid malabsorption in the regulation of plasma plant sterol levels was studied in 30 patients with an ileal resection (seven without any malabsorption, eight with bile acid malabsorption alone and 15 with bile acid, fat and cholesterol malabsorption) and nine with jejunoileal bypass (modest bile acid, and severe cholesterol and fat malabsorption). In contrast to cholesterol, plant sterols are not synthesized by the body, and so the plasma levels are regulated by their intestinal absorption and biliary secretion. In fact, the plant sterol, especially campesterol, levels were low in patients with cholesterol and fat malabsorption. Cholesterol absorption efficiency was a significant determinant of the plant sterol levels, suggesting that it reflects overall sterol absorption efficiency and that the plasma plant sterol levels, in turn, reflect cholesterol absorption. Bile acid malabsorption, though it appeared to promote biliary plant sterol secretion, had little direct effect on the plasma plant sterol contents. The results indicate that plasma campesterol levels can be used to evaluate cholesterol absorption efficiency in general and may reveal clinically significant steatorrhoea in patients with gut exclusion.     

Increased serum amylase and lipase in fructose malabsorbers

BACKGROUND: Fructose malabsorption is frequently seen in the general population and is characterised by the inability to absorb fructose efficiently. Due to fructose malabsorption, fructose reaches the colon where it is broken down by bacteria to short fatty acids, CO(2) and H(2). Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequence. We recently found that fructose malabsorption is associated with low plasma folic acid concentrations and low serum tryptophan and zinc. Because fructose malabsorption apparently is associated not only with malabsorption of other nutrients, but also with abdominal discomfort, it was of interest to examine whether mild pancreatitis may be involved. METHODS: We retrospectively examined our data in 159 otherwise healthy adults (110 females, 49 males) aged 14-84 years (mean 45.6+/-14.4 S.D.) with gastrointestinal complaints for serum amylase and serum lipase concentrations. The patients have been tested earlier for fructose malabsorption and lactose maldigestion by measuring breath H(2) concentrations after an oral dose of 25 g fructose and 50 g lactose, respectively, 1 week apart. RESULTS: Fructose malabsorption (H(2) concentrations > or =20 ppm over baseline values) was detected in 107 of 159 individuals (67.3%). These subjects with fructose malabsorption presented with significantly higher serum amylase concentrations (73.1 U/l+/-25.7 S.D.) compared to individuals with normal fructose absorption (59.6 U/l+17.9 S.D; p=0.0009). Fructose malabsorbers also presented with higher serum lipase concentrations (122.0 U/l+/-100.3 S.D.) compared to normals (89.5 U/l+/-46.5 S.D.; p<0.05). To determine whether this finding is a consequence of any sort of malabsorption syndrome or whether it is specific for fructose malabsorption, all subjects were screened for lactose maldigestion. Lactose maldigestion (H(2) concentrations>20 ppm over baseline after lactose loading) was found in 50 of 159 individuals (31.4%). There were no significant differences in either amylase or lipase concentrations in lactose maldigestors. CONCLUSION: Serum amylase and lipase concentrations are higher in subjects with fructose malabsorption compared to normals. Therefore, fructose malabsorption should be considered as a differential diagnosis in moderately elevated serum amylase.     

Clinical value of the bile acid breath test. Evaluation of the Mayo Clinic experience

The Mayo Clinic experience with more than 200 bile acid breath tests was analyzed retrospectively to assess its clinical value. In patients with suspected bacterial overgrowth, the result of the bile acid breath test was compared with that of culture of aspirates of small bowel, and the test was found to have a sensitivity of 0.70 and a specificity of 0.90 (1.0 highest possible value). Although in one-third of the patients with a positive small-bowel culture the bile acid breath test failed to demonstrate the presence of bacterial overgrowth, analysis of the data according to the Bayes theorem showed that, compared with a routine evaluation without a small-bowel culture, the availability of breath test results will double the probability with which the clinician can be certain about the presence or absence of bacterial overgrowth. The test result appeared to influence the diagnosis in 83% and the management in 74% of the 163 patients in whom it was performed because of suspected bacterial overgrowth. In patients with suspected malabsorption of bile acids, on the other hand, the test that was performed without determination of fecal bile acid excretion appeared to be rather insensitive, and only rarely was information gained that was not already known from a routine workup of the patient.     

Alpha heavy-chain disease in southern Iran.

A prospective study of 32 patients with primary upper small intestinal lymphoma in our region revealed 10 cases of alpha heavy-chain disease. Patients were mostly in the second and third decades of life and males predominated. Weight loss, diarrhea, and abdominal pain were the most common complaints and clubbing the most frequent physical findings. Laboratory tests revealed a malabsorption pattern on intestinal x-rays, and malabsorption of xylose, fat, and vitamin B12 was frequently noted. Dense plasmacytic infiltrate of the lamina propria of small bowel was the most frequent pathologic finding while true neoplasm of the lymphoid system (ie, immunoblastic sarcoma) was encountered in 20% of the cases.     

Galantase (beta-galactosidase) treatment in pediatric practice

The authors diagnosed lactose malabsorption by the breath hydrogen analysis in 11 premature and mature babies, in 16 infants and in 28 children between the ages of 3-18 years. All patients were treated with Galantase (beta-galactosidase). According to the results, Galantase is very effective in splitting of lactose of breast-milk, cow-milk and artificial formulas. Pathological hydrogen increase was not detected during the treatment.     

Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro.

Hydrogen produced by colonic bacteria and excreted in breath is a useful index of carbohydrate malabsorption. Since colonic contents are often acidic in individuals with carbohydrate malabsorption and in normal newborns, we determined the effect of colonic acidification on H2 production. Acidification of colonic contents by dietary means significantly reduced excess breath H2 excretion from 55.4 +/- 11.1 (SEM) to 12.2 +/- 3.1 ml/4 h (P less than 0.05) after administration of 0.3 g/kg of the nonabsorbable sugar lactulose to five normal adult subjects. Similarly, the breath H2 response to lactose was reduced or eliminated in two proven lactose malabsorbers after acidification. The correlation between pH and H2 production from carbohydrate was further investigated in adults and neonates, using an in vitro fecal incubation system. Glucose disappearance and H2 production were pH dependent and highly correlated (r = 0.94) in the pH range 5.5-7.6. Maximal production of H2 from glucose by fecal incubates occurred at pH 7.0-7.45. Inhibition of H2 production from carbohydrate occurred at acid pH. H2 per hour from glucose at pH 6.2 and 5.5 averaged 60.2% and 24.2%, respectively, of that produced at neutral pH. Rapid reversal of pH-induced inhibition by neutralization indicated a metabolic, rather than a bactericidal process. The observations indicate that the breath H2 response to malabsorbed carbohydrate is affected by colonic pH. It appears that the efficiency of bacterial carbohydrate metabolism in the colon is pH dependent.     

Bile acid metabolism in ileostomy patients

In ten ileostomy patients, a 14C-cholylglycine breath test was performed. The 14CO2 in the exhaled air and the 14C bile acid quantity and composition and fat content in the subsequent 24 h ileostomy effluent were determined and compared to the values in twenty healthy controls. The results show that in ileostomy patients only minor bile acid-deconjugation occurs in vivo. Deconjugation in the ileostomy bags was found to be mainly responsible for the absence of conjugated bile acids in many of the ileostomy effluent samples. Secondary bile acids were not present in these patients, as determined by TLC. The fecal fat and bile acid excretion was found to be in the normal range in ileostomy patients provided no concomitant ileum resection was present.