Comparison of indirect diagnostic methods for hypolactasia

The aim of this study was to continue our previously published work and to compare the different indirect diagnostic methods for hypolactasia with the lactase to sucrase ratio obtained by jejunal biopsy. The following tests were performed in 63 adult patients: the breath hydrogen test, the lactose tolerance test with ethanol (serum galactose measurement after oral lactose load with ethanol), the urinary lactose tolerance test (urinary galactose measurement after oral lactose load with ethanol), and the strip test (like the former but using a special test strip for urinary galactose). Specificities of all these tests were good (96-98%). The 3-h breath hydrogen test was less sensitive (69%) than the other methods (81-94%). The strip test is recommended for the general practitioner for the diagnosis of this common cause of abdominal complaints.     

Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis

Lactose malabsorption was studied, by hydrogen breath test, in 72 adults suffering from irritable bowel syndrome, in 20 ulcerative colitis patients, and in 69 healthy subjects. The minimum dose of lactose required to cause a positive breath test was determined, and the symptoms caused and the resulting hydrogen eliminated quantified. A high incidence of lactose malabsorption was shown at standard doses (up to 50 g) in both the healthy subjects (70%) and the patients (86% and 85%, respectively). In the irritable bowel syndrome and the ulcerative colitis groups, symptoms occurred with a smaller quantity of breath hydrogen, presumably in association with a greater individual sensitivity of the colon to distension. The threshold lactose dose was notably lower in the diseased subjects who registered as evidence a prevalence of malabsorption at a 20-g lactose load. The pathogenetic role of lactose malabsorption in the irritable bowel syndrome is emphasized, as is the importance of the personal lactose tolerance.     

Methodology of the H2 breath test. II. Importance of the test duration in the diagnosis of carbohydrate malabsorption

We analyzed the results of 352 consecutive four-hour lactose hydrogen breath tests with the aim of verifying whether the results after two hours have the same accuracy as those after four hours in the diagnosis of malabsorption of 20g of lactose. Our results show that in 208 subjects who proved to be lactose malabsorbers the mean changes in breath H2 concentration were higher at three and a half hours than at any other time. Moreover, although the majority of the subjects (63%) reached the cut-off value (more than 20 parts per million with respect to the baseline value) in the first two hours of the test, in 76 of our 208 lactose malabsorbers (37%) a hydrogen increase higher than the cut-off value is only detectable after the second hour of the test. Therefore, unlike those who believe that two samples of expired air at 0 time and after two hours are sufficient, we think that for greater diagnostic accuracy the lactose H2 breath test must be prolonged for at least 4 hours.     

Breath testing to evaluate lactose intolerance in irritable bowel syndrome correlates with lactulose testing and may not reflect true lactose malabsorption

OBJECTIVES: An increased prevalence of lactose intolerance is seen in irritable bowel syndrome (IBS). Recently, we demonstrated a high prevalence of abnormal lactulose breath test results in IBS suggesting bacterial overgrowth. Because symptoms of lactose intolerance result from bacterial fermentation, the purpose of this study was to determine whether an abnormal lactose breath test is reflective of malabsorption or early presentation to bacteria. METHODS: Subjects with diarrhea-predominant IBS were enrolled. On day 1, subjects underwent a lactulose breath test after an overnight fast. Within 1 wk, subjects returned after fasting for a lactose breath test with simultaneous blood glucose measurements every 15 min to complete a lactose tolerance test (LTT). Symptoms were evaluated 3 h after lactose administration. RESULTS: Twenty subjects completed the study. One subject inadvertently received dextrose through the intravenous and was excluded. Of the remaining 19 subjects, three (16%) had an abnormal LTT suggesting malabsorption. In all, 10 subjects (53%) had an abnormal lactose breath test, 14 (74%) had an abnormal lactulose breath test, and 11 (58%) had symptoms after lactose administration. The agreement with symptoms was moderate (kappa = 0.47) and fair (kappa = 0.24) when compared to the lactose breath test and LTT, respectively. There was a fair correlation between lactose breath test and LTT (kappa = 0.29). However, lactose breath test hydrogen levels >166 ppm were universally predictive of abnormal LTT. Finally, a significant correlation was seen between the hydrogen production on lactose and lactulose breath test (r = 0.56, p = 0.01). CONCLUSIONS: Lactose breath testing in IBS subjects does not seem to reflect malabsorption; it may be an indicator of abnormal lactulose breath test, suggesting bacterial overgrowth.     

Strip test is reliable in common prevalences of hypolactasia

The object of this study was to compare the indirect diagnostic methods on the basis of urinary galactose determination in the diagnosis of lactose malabsorption with the actual lactase activities. One hundred and seven patients were studied. The specificity and sensitivity of the strip test were 97%. With 30% actual prevalence the positive predictive value was 94%, and the negative predictive value was 99%. In common prevalences of hypolactasia the strip test was reliable.     

Lactose tolerance despite hypolactasia in adult coeliac disease

Although symptoms of milk intolerance are common in primary (genetically determined) hypolactasia it is a clinical impression that such symptoms are infrequent in adult patients with hypolactasia secondary to damage of the mucosa of the small intestine. This study was designed to determine whether a lactose (50 g) challenge is better tolerated by patients with coeliac disease and secondary hypolactasia than patients with primary hypolactasia. Based on intestinal histology and disaccharidase levels, three groups of adults were studied: controls ( n = 20), patients with primary hypolactasia ( n = 20) and patients with hypolactasia secondary to newly diagnosed coeliac disease ( n = 15). The response to a challenge with 50 g lactose was assessed by a score of five symptoms and breath hydrogen production. Despite an equivalent level of hypolactasia, symptoms affected fewer patients with coeliac disease (33%) than subjects with primary hypolactasia (90%). Further, a positive lactose breath hydrogen test was noted in all (100%) patients with primary hypolactasia but in only six (40%) of those patients with newly diagnosed coeliac disease. These results suggest the presence of a considerable absorptive reserve for lactose in the distal small bowel of many patients with coeliac disease.     

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.     

Prevalence of lactose malabsorption among patients with functional bowel disorders

To investigate the prevalence of lactose malabsorption among patients with functional gastrointestinal disturbances we prospectively evaluated all patients referred to a gastrointestinal outpatient clinic over a period of 18 months. All patients had a breath hydrogen test following oral lactose in addition to the standard diagnostic procedures. In 37 of the total of 64 patients no organic cause of the gastrointestinal complaints was found. In 9 of these 37 patients (24%) the breath hydrogen test indicated lactose malabsorption. Three to 6 month later most of the patients with lactose malabsorption showed a significant reduction of gastrointestinal complaints after they had maintained a lactose-poor diet. In comparison, patients with functional disturbances but without lactose malabsorption reported nor or only minor improvement of symptoms; most of these patients had consulted another physician since the last visit in the clinic.     

Genetic test for lactase non-persistence and hydrogen breath test: Is genotype better than phenotype to diagnose lactose malabsorption?

BackgroundAdult-type hypolactasia is a widespread condition throughout the world, causing lactose malabsorption. The lactose breath test is a simple tool for diagnosis but the need for prolonged monitoring of hydrogen excretion has led to a genetic test proposal. The aim of this study was to compare the genetic test with the lactose breath test in order to give some insights into the clinical value of genetic testing.MethodsThirty-two consecutive functional patients underwent lactose breath test and lactase genetic polymorphism analysis (C/T 13910 and G/A 22018). Intolerance symptoms after lactose load were also monitored.ResultsAll patients with positive lactose breath test showed homozygosis for both polymorphisms. Among the nine patients with a negative breath test result, six showed heterozygosis while three showed homozygosis. Intolerance symptoms were present in 16 homozygotic patients but also in one heterozygotic patient. The k value for the agreement between the genetic test and the lactose breath test was 0.74.ConclusionA positive genetic test for lactase non-persistence indicates whether lactase activity decline may represent a clinical problem for the patient, but does not give information on actual patient symptoms. On the contrary, this information is already available by combining the lactose breath test with intolerance symptom evaluation. Lactose absorption phenotype may be not yet evident until young adult age.     

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.     

Seventy-five gram glucose tolerance test to assess carbohydrate malabsorption and small bowel bacterial overgrowth

AIM: To investigate non-invasively the incidence of absorption of carbohydrates in diabetic patients during an oral glucose tolerance test (OGTT) and to determine whether malabsorption may be associated with insulin secretion and insulin resistance. METHODS: A standard 75-g OGTT was performed in 82 diabetic patients. The patients received 75 g of anhydrous glucose in 225 mL of water after an overnight fasting and breath samples were collected at baseline and up to 120 min after ingestion. Breath hydrogen and methane concentrations were measured. Blood glucose and serum insulin concentrations were measured before ingestion and at 30, 60, 90, 120 min post-ingestion. RESULTS: When carbohydrate malabsorption was defined as subjects with an increase of at least 10 ppm (parts per million) in hydrogen or methane excretion within a 2-h period, 28 (34%) had carbohydrate malabsorption. According to the result of increased breath test, 21 (75%) patients were classified as small bowel bacterial overgrowth and 7 (25%) as glucose malabsorption. Patients with carbohydrate malabsorption were older and had poor glycemic control as compared with those without carbohydrate malabsorption. The HOMA value, the sum of serum insulin during the test and the Ainsulin/Aglucose ratio were greater in patients with carbohydrate malabsorption. CONCLUSION: Insulin resistance may be overestimated by using these markers if the patient has carbohydrate malabsorption, or that carbohydrate malabsorption may be present prior to the development of insulin resistance. Hence carbohydrate malabsorption should be taken into account for estimating insulin resistance andβ-cell function.     

Lactose malabsorption and intolerance: What should be the best clinical management?

Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a wellknown cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake. Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.     

Implementation and interpretation of hydrogen breath tests

Hydrogen breath tests are non-invasive and safe diagnostic tools used to investigate functional intestinal disorders. For the diagnosis of fructose or lactose malabsorption as well as for the detection of small intestinal bacterial overgrowth syndrome, hydrogen breath tests are even regarded as gold standard. However, standardization of the testing procedure and the interpretation of the test results are still lacking. In this paper, reliable information on the implementation of the most common hydrogen breath tests and precise guidelines for the interpretation of the test results are presented.     

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.     

A Diagnostic Approach to Patients with Suspected Lactose Malabsorption

Background

The lactose breath test (LBT) is the standard technique for diagnosis of lactose malabsorption. However, it is time-consuming, strenuous for the patient and has been reported to have low sensitivity. The lactose intolerance quick test (LIQT) measures lactase activity in duodenal biopsies and may be performed as part of upper gastrointestinal endoscopy.

Aim

The purpose of this study was to assess the role of the LBT and LIQT in the case management of suspected lactose malabsorption.

Methods

The study group included 69 consecutive patients evaluated by the LBT followed by the LIQT. The test results were compared, and the sensitivity, specificity, and predictive values of the LBT were calculated.

Results

Mean age of the patients was 54.4 years, male/female ratio was 1:3, and mean body mass index was 25.2. None had celiac disease on duodenal biopsy. The LIQT was positive for hypolactasia in 55 patients (80 %): mild in 14 (25 %) and severe in 41 (75 %); 10 (18 %) were symptomatic during the LBT. The LBT was positive for lactose malabsorption in 32 patients (46 %). Of the 37 patients with normal findings on the LBT, 24 (65 %) had positive findings on the LIQT: 11 (30 %) mild hypolactasia, 13 (35 %) severe hypolactasia. In one case, the LBT was positive and the LIQT was negative. The LBT had a sensitivity of 56 %, specificity 93 %, positive predictive value 97 %, and negative predictive value 35 %.

Conclusions

The LBT may serve as a diagnostic screening tool for lactose malabsorption. Symptomatic patients with negative LBT results should be referred for second-line testing with the LIQT.     

Hypolactasia in Japanese Crohn's patients]

20 g lactose load test, BHT and LTT done simultaneously were examined in 32 Crohn's disease patients and 51 healthy volunteers. Hypolactasia frequency were examined. A rise in hydrogen concentration > 20 parts per million (ppm) above the base line during breath hydrogen test and maximum blood sugar rise during lactose tolerance test were considered to indicated Hypolactasia. High rates, 50% by BHT and 72.5% by LTT, of primary adult hypolactasia were found in healthy volunteers as previously reported. Higher rates, 83.3% by BHT and by LTT (p < 0.05), were observed in Crohn's disease patients. There were higher rates in small intestine type Crohn's disease (91.6% by BHT, 92.3% by LTT) compare with healthy volunteers but no difference were found with large intestine type Crohn's disease.     

Effects of age on lactose malabsorption in Oklahoma Native Americans as determined by breath H2 analysis

Breath H₂ excretion was used to determine lactose malabsorption in 30 healthy females and 30 healthy males between the ages of 3 and 64 yr who were at least 7/8 Native American. The test meal consisted of 5 ml reconstituted nonfat dry milk (0.25 g lactose) per kg of body weight. On the basis of breath H₂ tests in 15 control subjects with normal oral lactose tolerance tests, a response factor of 20 ppm was selected as the upper limit for lactose absorbers. Of the 60 subjects in the study group, 36 (60%) were classified as lactose malabsorbers since they had a response factor of 20 ppm or greater of breath H₂. Only 3 of 20 children (15%) who were under the age of 12 yr were nondigesters of the small lactose dose used in this study. Approximately 82 percent (82.5%) of subjects who were 13 yr and older were lactose malabsorbers. Adolescence appears to be the period in which malabsorption of lactose becomes evident in Native North Americans.Supported by the Nutrition Foundation, Inc., New York, New York; Biomedical Sciences Support Grant (USPH) 5-S05-RR7077 to The Research Foundation, Oklahoma State University.     

Study of malabsorption of lactose by the hydrogen breath test in a population of 70 Tunisian adults

Lactose malabsorption was studied by the hydrogen breath-test in 23 adults suffering from irritable bowel syndrome (group A) and in 47 healthy subjects (group B). The concentration of hydrogen in end-expired alveolar samples was measured after ingestion of 25 g of lactose. Among the 70 subjects, 6 (8.5 p. 100) were not hydrogen producers and were excluded from the study. Lactose malabsorption was shown in 51 of the remaining 64 subjects (79.6 p. 100). Among these 51 patients, 36 were healthy and 15 had an irritable bowel syndrome. The frequency of lactose malabsorption among the 43 healthy hydrogen producers was 83 p. 100. This value is similar to those observed in other studies (greek and italian). Our results suggest that lactose malabsorption is frequent among the tunisian adult population.     

Hydrogen breath test for the diagnosis of lactose intolerance, is the routine sugar load the best one？

AIM： To evaluate the prevalence of lactose intolerance （LI） following a load of 12.5 g in patients diagnosed as high-grade malabsorbers using the hydrogen breath test （HBT）-25. METHODS： Ninety patients showing high-grade malabsorption at HBT-25 were submitted to a second HBT with a lactose load of 12.5 g. Peak hydrogen production, area under the curve of hydrogen excretion and occurrence of symptoms were recorded. RESULTS： Only 16 patients （17.77%） with positive HBT-25 proved positive at HBT-12.5. Hydrogen production was lower as compared to HBT-25 （peak value 21.55 parts per million （ppm） ± 29.54 SD vs 99.43 ppm ± 40.01 SD; P 〈 0.001）. Symptoms were present in only 13 patients. The absence of symptoms during the high-dose test has a high negative predictive value （0.84） for a negative low-dose test. The presence of symptoms during the first test was not useful for predicting a positive low-dose test （positive predictive value 0.06-0.31）. CONCLUSION： Most patients with a positive HBT-25 normally absorb a lower dose of lactose and a strict lactose restriction on the basis of a ＂standard＂ HBT is, in most instances, unnecessary. Thus, the 25 g lactose tolerance test should probably be substituted by the 12.5 g test in the diagnosis of LI, and in providing dietary guidelines to patients with suspected lactose malabsorption/intolerance.     

The use of breath tests in the study of malabsorption

Breath analysis has evolved into a technique that can support nicely the evaluation of patients with diarrhoea and/or weight loss and in whom nutrient malabsorption is a possibility. The lactose and sucrose breath hydrogen tests offer direct (and probably the most sensitive) documentation of the malabsorption of carbohydrate and are currently widely used for clinical analysis. The 14C-xylose breath test is the most sensitive and specific breath test for detecting bacterial overgrowth; it may be used in combination with the labelled bile acid breath test to make the latter a sensitive and specific test for ileal malabsorption of bile salts. The labelled fat breath test has promise in aiding the detection and/or cause of fat malabsorption, but requires modification for optimum sensitivity and utility in quantifying the level of fat absorption.