Variations in colonic H2 and CO2 production as a cause of inadequate diagnosis of carbohydrate maldigestion in breath tests

BACKGROUND: Lactose maldigestion is usually diagnosed by means of the H2 breath test. When 13C-lactose is used as substrate, a 13CO2 breath test can be performed simultaneously. In an earlier publication we described the relation between both the H2 and 13CO2 exhalation in breath and the measured intestinal lactase activity after consumption of 13C-lactose. We found a discrepancy between both breath test results in 36% of the cases. To investigate the possible cause of these incongruous breath test results, we studied gas production from carbohydrate in the colon, using 13C-lactulose as a non-absorbable substrate. METHODS: Experiments were performed in 21 subjects, by applying 5 different doses of 13C-lactulose. Repeatability studies were performed in six of these subjects, using 10 g substrate (three tests with 1-week intervals). RESULTS: Both the H2 and the 13CO2 excretion in breath varied strongly interindividually and intraindividually after consumption of 13C-lactulose. In both cases no dose-response relation was observed. A significant positive linear relationship was found between H2 and 13CO exhalation (r = 0.45, P < 0.005). Extrapolation of these results to 13C-lactose breath tests indicates that the colonic contribution of 13CO2 production to the total 13CO2 excretion in breath varies but is on the average large enough to cause false-negative 13CO2 breath test results. CONCLUSIONS: Excretion in breath of 13CO2 produced in the colon during a 13C-lactulose breath test correlates with the breath H2 excretion. This could explain the occurrence of false-negative 13CO2 lactose breath tests when colonic gas production is high and false-negative lactose H2 breath test results when gas production is low. It can also explain the improved sensitivity of the combined H2/13CO2 lactose breath test compared with both breath tests alone.     

13C-Carbohydrate Breath Tests: Impact of Physical Activity on the Rate-Limiting Step in Lactose Utilization

Background: ¹³CO₂ breath tests can be used to monitor carbohydrate digestion in the small intestine. However, after ingestion of ¹³C-substrates, ¹³CO₂ excretion in breath originates from two sources: a digestive/oxidative fraction, derived from the small intestine, and a fermentation fraction, derived from undigested substrate spill-over in the colon. In this study, the determinants of the digestive/oxidative fraction were analysed in order to improve the sensitivity/specificity of the ¹³C-carbohydrate breath tests. Methods: ¹³C-carbohydrate breath tests were performed in healthy adults using ¹³C-lactose, pre-digested ¹³C-lactose, ¹³C-glucose, and ¹³     

Non-Invasive Detection of Low-Intestinal Lactase Activity in Children by Use of a Combined 13CO2/H2 Breath Test

Background: The aim of the study was to diagnose hypolactasia with a higher accuracy than with the traditional H₂ breath test. Methods: We used a combined ¹³C-lactose ¹³CO₂/H₂ breath test, which was performed in 33 patients in whom lactase activity was measured. Results: Lactase activity was reduced in 13 cases. The sensitivity and specificity of the H₂ test were 54% and 90%; those of the ¹³CO₂ test 69% and 70%. False-negative results did not always occur in the same patients. In five of six patients with both test results abnormal, lactase activity was low. In 13 of 15 patients with both test results normal, lactase activity was normal. In 6 of 12 cases with only 1 test abnormal, lactase activity was low. Conclusion: The combined H₂/¹³CO₂ breath test (sensitivity, 85%; specificity, 65%) is more adequate for diagnosis of hypolactasia than the H₂ breath test alone.     

13C-carbohydrate breath tests: impact of physical activity on the rate-limiting step in lactose utilization

BACKGROUND: 13CO2 breath tests can be used to monitor carbohydrate digestion in the small intestine. However, after ingestion of 13C-substrates, 13CO2 excretion in breath originates from two sources: a digestive/oxidative fraction, derived from the small intestine, and a fermentation fraction, derived from undigested substrate spill-over in the colon. In this study, the determinants of the digestive/oxidative fraction were analysed in order to improve the sensitivity/specificity of the 13C-carbohydrate breath tests. METHODS: 13C-carbohydrate breath tests were performed in healthy adults using 13C-lactose, pre-digested 13C-lactose, 13C-glucose, and 13C-galactose as substrates. The effect of exercise (bicycling, 50 W), increasing the metabolism of digested/absorbed substrate, on the outcome of the test was analysed. RESULTS: In rest, no difference was observed in the 4-h cumulative percentage dose recovered in breath (4-h cPDR) after administration of glucose, pre-digested lactose, and lactose, which were 20.3 +/- 4.5%, 19.2 +/- 5.5%, and 19.9 +/- 4.9%, respectively. The 13CO2 excretion rate after 13C-galactose consumption was significantly slower than after 13C-glucose consumption. Exercise increased 4-h cPDR of 13C-glucose significantly: 76.0 +/- 1.0% vs. 22.7 +/- 2.3%. This effect was also observed using 13C-lactose as substrate: 66.1 +/- 6.2% vs. 19.6 +/- 3.9%. One subject had non-symptomatic lactose maldigestion indicated by a positive H2 breath test. The 13CO2 breath test of this subject in rest was indistinguishable from that of the others (4-h cPDR 16.6 vs. 19.6 +/- 3.9%), whereas the test was clearly indicative during exercise (4-h cPDR 20.5 vs. 66.1 +/- 6.2%). CONCLUSION: In healthy volunteers in rest, glucose oxidation is the rate-limiting step in lactose conversion into 13CO2. Increase of metabolism (for instance, by exercise) can shift this step to intestinal hydrolysis of lactose, making the 13C-lactose breath test more sensitive.     

Comparison of the one-gramd-[14C]xylose breath test to the [14C]bile acid breath test in patients with small-intestine bacterial overgrowth

In twelve patients with culture-proven bacterial overgrowth of the small intestine, the ability of a newly-developed one-gramd-[¹⁴C]xylose breath test to detect bacterial overgrowth was compared to that of the [¹⁴C]bile acid breath test. All patients manifested excessive production of breath¹⁴CO₂ after the administration of one gram [¹⁴C]xylose, with 83% of the patients being abnormal within the first hour of testing. In contrast, during the [¹⁴C]bile acid breath test, four of the twelve patients had no period of excessive¹⁴CO₂ production (above the 95% confidence range of controls). Nutrient malabsorption (fat, cobalamin, xylose) was seen with both true-positive and false-negative bile acid breath tests. The one gram [¹⁴C]xylose breath test, utilizing a substrate with more predominant absorption in the proximal small intestine and which can be catabolized by Gram-negative aerobic bacteria, appears to have a greater degree of sensitivity and specificity than the bile acid breath test in detecting the presence of small-intestine bacterial overgrowth.Dr. King is the recipient of a Research Associate Award from the Veterans Administration. During the performance of these studies Dr. Toskes was the recipient of a Clinical Investigator Award from the Veterans Administration.Supported in part by Grant #RR-82 from the National Institutes of Health.     

Follow-up of coeliac disease with the novel one-hour 13C-sorbitol breath test versus the H2-sorbitol breath test

Abstract

Background. We recently developed a ¹³C-sorbitol breath test (¹³C-SBT) as an alternative to the H₂-sorbitol breath test (H₂-SBT) for coeliac disease. In this study we compared the diagnostic properties of the H₂-SBT and the ¹³C-SBT in follow-up of coeliac disease. Material and methods. Twenty-seven coeliac patients on a gluten-free diet (GFD) performed the breath tests. All had been tested before treatment in the initial study of the ¹³C-SBT, in which 39 untreated coeliac patients, 40 patient controls, and 26 healthy volunteers participated. Five gram sorbitol and 100 mg ¹³C-sorbitol were dissolved in 250 ml tap water and given orally. H₂, CH₄ and ¹³CO₂ were measured in end-expiratory breath samples every 30 min for 4 h. Increased H₂ concentration ≥20 ppm from basal values was used as cut-off for the H₂-SBT. Sixty minutes values were used as diagnostic index in the ¹³C-SBT. Results. ¹³CO₂ levels at 60 min increased in 20/26 treated coeliac patients (77%) after GFD, but were significantly lower than in control groups. Out of 20 patients who had a positive H₂-SBT before GFD, 12 had a negative H₂-SBT after GFD. Peak H₂ concentrations were not correlated with ¹³C-SBT results. Conclusion. The study confirms the sensitivity of a one-hour ¹³C-SBT for small intestinal malabsorption. The ¹³C-SBT has superior diagnostic properties compared with the H₂-SBT in follow-up of coeliac 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.     

Mitochondrial Function Reflected by the Decarboxylation of [13C]Ketoisocaproate Is Impaired in Alcoholics

Mitochondria of patients with alcoholic liver disease exhibit structural abnormalities, and mitochondria isolated from animals exposed to ethanol are functionally deficient when studied in vitro. To assess possible functional consequences of these ethanol-associated alterations in vivo, we measured mitochondrial function in alcoholics noninvasively with a breath test. A mitochondrial function, the decarboxylation of ketoisocaproate (KICA), was assessed by measuring the exhalation of ¹³CO₂ following the administration of 1 mg/kg 2-keto[1-¹³C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the KICA breath test in 12 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of ¹³CO₂ and the fraction of the administered dose decarboxylated in 120 min were both significantly lower in alcoholics than in healthy controls and patients with nonalcoholic liver disease. In alcoholics, KICA decarboxylation was impaired in the presence of normal quantitative liver function tests such as the aminopyrine breath test and galactose elimination capacity, indicating that KICA decarboxylation does not simply reflect a decreased functional hepatic mass. The enrichment of circulating KICA with [¹³C]KICA was similar in alcoholics and controls, indicating that a decreased bioavailability or an increased dilution of labeled KICA cannot account for the decreased exhalation of ¹³CO₂ It is concluded that mitochondrial function as reflected by KICA decarboxylation is impaired in chronic alcoholics. The functional impairment is specific for ethanol abuse and not a reflection of decreased global hepatic function. KICA decarboxylation could thus be useful as a marker for excessive ethanol consumption.     

Role of Circulating Peptide YY in the Inhibition of Gastric Acid Secretion by Dietary Fat in Humans

Objectives. Xylose absorption testing has traditionally involved measurement of serum xylose and/or measurement of excreted xylose in urine. However, by enriching xylose with a ¹³C- or ¹⁴C-isotope, absorption of an oral xylose load will be reflected in the time-dependent pattern of ¹³CO₂ or ¹⁴CO₂ exhaled in breath. Our objectives were to evaluate the diagnostic properties of ¹³C-xylose and ¹⁴C-xylose breath tests in coeliac disease, and to develop a diagnostic breath test index. Material andmethods. We reviewed data from 41 coeliac patients who underwent the ¹⁴C-xylose breath test before and after commencement of a gluten-free diet, and 60 coeliac patients who underwent the ¹³C-xylose breath test, 37 of whom repeated the test after starting a gluten-free diet. Coeliac patients were compared with healthy control subjects. Results. Coeliac patients exhaled significantly less ¹³CO₂ or ¹⁴CO₂ than healthy controls during the first hour of the test and more isotope-labelled CO₂ than control subjects after 3 h. Diagnostic accuracy was optimal with test duration of 210 min combining gas measurements at 30 min and 210 min in a simple fraction. This gas fraction index (30 min/210 min) distinguished between coeliac patients and healthy control subjects with 84–95% sensitivity and 87–94% specificity. After commencement of a gluten-free diet, the gas fraction index increased in most coeliac patients, but remained lower than that in healthy control subjects. Conclusions.¹³C-xylose- and ¹⁴C-xylose breath tests discriminate between coeliac patients and healthy control subjects with high sensitivity and specificity. The stable isotope ¹³C-xylose breath test has comparable diagnostic accuracy to the radioactive isotope ¹⁴C-xylose breath test and should be the preferred alternative to traditional xylose absorption tests.     

A novel one-hour13C-sorbitol breath test versus the H2-sorbitol breath test for assessment of coeliac disease

Objective. The H₂-sorbitol breath test (H₂-SBT) has previously been suggested as a screening tool for coeliac disease. We developed an alternative ¹³C-sorbitol breath test (¹³C-SBT). The aim of the study was to compare the diagnostic properties of the H₂-SBT and the ¹³C-SBT in a clinical setting. Material and methods. Thirty-nine coeliac patients, 40 patient controls (mainly patients with irritable bowel syndrome) and 26 healthy volunteers underwent the breath tests. The patients were given an oral load of 5 g sorbitol and 100 mg ¹³C-sorbitol dissolved in 250 ml tap-water. H₂, CH₄ and ¹³CO₂ concentrations were measured in end-expiratory breath samples every 30 min for 4 h. Increased H₂ concentration ≥20 ppm from basal values was used as the cut-off for the H₂-SBT. Results. The H₂-SBT had a sensitivity of 71%, a specificity of 46% versus healthy controls, and a specificity of 25% versus patient controls. Individuals with methane-producing intestinal flora had significantly lower peak H₂ concentrations than non-methane producers. The ¹³C-SBT reached maximal combined sensitivity/specificity (74%/85%) for both control groups after 1 h. A diagnostic algorithm which stratified patients into high-, moderate- and low risk for coeliac disease was proposed. Following the algorithm, 62% of coeliac patients were detected with 100% specificity. The ¹³C-SBT, but not the H₂-SBT, correlated with age and serum IgA tissue-transglutaminase antibody levels in coeliac patients. Conclusions. The novel ¹³C-SBT has superior diagnostic properties compared to the H₂-SBT, which has unsatisfactory specificity in clinical practice. The 1-h ¹³C-SBT may be a useful supplemental test when investigating for coeliac disease.     

Efficacy of lactulose plus <Superscript>13</Superscript>C-acetate breath test in the diagnosis of gastrointestinal motility disorders

Background: Background: We designed a new method of measuring gastric emptying and orocecal transit time (OCTT) at the same time to assess the influence of gastric emptying upon OCTT. Methods: Twenty-five dyspeptic patients (6 men, 19 women) with a mean age of 64.8 years (range, 25–80 years) were studied. The patients received a liquid test meal, containing 100 mg of ¹³C-acetate and 12 g of lactulose, while they were in the sitting position after an overnight fast. Breath samples were collected at 10-min intervals of 120 min and both ¹³CO₂ and hydrogen (H₂) levels were measured. Subsequently, H₂ concentrations were measured at 30-min intervals, for a total of 240 min. Results: The results of gastric emptying were expressed as the time of peak ¹³CO₂ excretion. OCTT was defined as the period between the ingestion of lactulose and a H₂ peak rise of 5 ppm above the baseline value. The onset of H₂ enrichment in the breath began at 90–110 min, whereas ¹³CO₂ levels increased from the beginning, with peak enrichment values being reached after 60–80 min. OCTT was related to ¹³CO₂ peak time. In 5 of the 25 patients, H₂ breath enrichment in the 10-min sample was more than 5 ppm over the baseline value. All these 5 patients had double or triple peaks in serial breath H₂ concentrations. Conclusions: The combination of the lactulose hydrogen breath test (LHBT) with the ¹³C-acetate breath test, which requires only breath samples, provides us with much information on the gastrointestinal tract; gastric emptying, OCTT, bacterial overgrowth in the small intestine, colonic fermentation, and oropharyngeal flora. The ¹³C-acetate breath test can be useful as an adjuvant test when LHBT is performed for measuring OCTT. Received: March 5, 2001 / Accepted: October 5, 2001     

The stable isotope ketoisocaproic acid breath test as a measure of hepatic decarboxylation capacity: a quantitative analysis in normal subjects after oral and intravenous administration

Background and aims: There is no generally accepted kinetic evaluation method for the stable isotope [¹³C]ketoisocaproic acid (KIC) breath test. Differences found in the results between women and men are contradictory. Methods: Oral and intravenous breath tests using 1 mg/kg stable isotope‐labelled KIC were performed in healthy male and female volunteers. A power exponential function was fitted to the mass spectrometric data of breath ¹³CO₂ enrichment, allowing mathematical analysis of time‐to‐peak‐excretion, half‐excretion time, percent label recovery and parameters describing the shape of the curve. Body composition was determined using bioelectrical impedance analysis. Results: After oral administration, total label recovery after 3 h was about 22% and was not different between men (n=7) and women (n=8). The time to maximal label excretion was 0.67 ± 0.12 h in men and 0.9 ± 0.32 h in women (P=0.028) and the excretion curve showed an initially slower rise in women compared with men. Adjusting for lean body mass or body water abrogated the sex differences. Total label recovery after intravenous administration was about 9%, suggesting that the substrate was rapidly catabolized in the muscle compartment after intravenous administration. Conclusions: The modified power exponential function described allows standardized estimates of the KIC breath test results. When corrected for body composition, there are no differences in breath test results between men and women. The comparison between oral and intravenous results provides robust evidence that the KIC breath test measures predominantly hepatic and not muscle decarboxylation and is thus a highly specific liver function test.     

Reduced Accuracy of 14C-D-Xylose Breath Test for Detecting Bacterial Overgrowth in Gastrointestinal Motility Disorders

The accuracy of the ¹⁴C-D-xylose breath test in the diagnosis of small-bowel bacterial overgrowth was prospectively evaluated in 10 patients with motility disorders: 6 myopathic, 3 neuropathic, and 1 mechanical obstruction. Six of the 10 patients had small-bowel bacterial overgrowth (≥10⁵ colony-forming units/ml) on culture of small-bowel aspirate. Increased breath ¹⁴CO₂ levels were documented in three of six patients with positive cultures and in two of four with negative cultures. Two patients with positive results by both methods and one of two patients with positive breath ^l4CO₂ but negative cultures had previously undergone gastric surgery. Three patients with myopathic dysmotility had positive cultures but negative breath tests. Cultures of duodenal aspirates and the D-xylose test had sensitivities of 80% and 40%, respectively, for the finding of hypoalbuminemia. Compared with cultures, the sensitivity and specificity of the breath test were 60% and 40%, respectively. Impaired delivery of ^l4C-D-xylose for bacterial metabolism may result from postprandial antral hypomotility (n = 4) or low-amplitude (n = 6) small-bowel motility, contributing to the false-negative breath tests. Thus, culture is the optimal method to detect small-bowel bacterial overgrowth in patients with motility disorders.     

Simultaneous continuous 13C, 12C analysis of expired gas in the 13C breath test

The ¹³C breath test is a method of clarifying the metabolism of loaded substances by administering ¹³C-labelled materials and calculating the ¹³CO₂ and ¹²CO₂ ratio (¹³C/¹²C isotope ratio) in the expired gas. The materials are metabolized and expelled in the expired gas. Because simultaneous continuous measurement of ¹³CO₂ and ¹²CO₂ in expired gas has been difficult up to the present, respective expired gases, including dead space before and after administration, have been sampled to separate sampling bags and ¹³C/¹²C has been measured in the bags and changed fraction of ¹³C/¹²C after administration (δ) has been used to judge the metabolic process. This method is affected by the contamination of the dead space gas. In the present study, in order to exclude the dead space effect, simultaneous continuous analysis of ¹²CO₂ and ¹³CO₂ of expired gas identifying alveolar gas was applied to the ¹³C-urea breath test in addition to the conventional sampling bag method. Both isotope detectors were attached to a mass spectrometer. Fifty-six cases receiving stomach health check-ups for Helicobacter pylori were examined. δ was calculated in the bag or in phase III of continuous gas measurement. Because the bag contains dead space, δ was reduced and sensitivity and specificity with reference to gastric fluoroscopy or Helicobacter pylori IgG antibody were reduced. Decreasing the dead space contamination is important in reducing the measurement error in the ¹³C breath test and simultaneous continuous measurement is a good tool for this purpose.     

A Simple,Rapid, and Highly Reliable Capsule-based 14C Urea Breath Test for Diagnosis of Helicobacter pylori Infection

Background: Since the urea breath test (UBT) indirectly detects gastric Helicobacter pylori infection by measuring urease activity, the possibility of false-positive results due to other urease-producing bacteria cannot be excluded. Previous studies have shown that increased ¹⁴CO₂ activity in early breath samples could be attributed to urea hydrolysis in the oropharynx. For that reason, reliable assessment of H. pylori status is hampered for at least 20 min after administration of a ¹⁴C-urea drink. Methods: To overcome this problem, we have developed a modified breath test in which 111kBq ¹⁴C-urea is supplied in a gelatin capsule, which prevents release of ¹⁴C before reaching the stomach. Our modified ¹⁴C UBT was evaluated in 100 healthy volunteers, and results were compared with those from enzyme-linked immunosorbent assay serology. Results: The study showed a 99% concordance between the two non-invasive tests. When a biometric method for determination of cut-off values between positive and negative UBT results with the smallest possible arbitrariness was used, the calculated statistical probability of a false diagnosis was lowest in the 10-min breath sample (0.20%), and 100% sensitivity and specificity was achieved. Our capsule method was also compared with the urea drink method and was found more reliable because no overlapping in ¹⁴CO₂ activity occurred between H. pylori-positive and -negative subjects, whereas conventional breath testing showed overlapping during the whole 30-min test period. Our study also showed that a fatty test meal lowers the ¹⁴CO₂ excretion the first 20 min and may adversely affect the accuracy of a rapid UBT. Conclusions: Supplying the ¹⁴C-urea in a capsule obviates the problem of false-positive results in early breath samples and makes it possible to diagnose H. pylori infection with 99.8% reliability from a single 10-min breath sample, without the use of a test meal or adjustments for assumed individual CO₂ production.     

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of Δ-13CO2 using laser spectroscopy

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified ¹³C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The ¹³C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of ¹³C-urea administration. The ratio of ¹³CO₂ to ¹²CO₂ was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of ¹³C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of Δ-¹³CO₂. In 32 H. pylori-negative patients (without therapy), the mean ± 2SD of Δ-¹³CO₂ was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean ± SD Δ-¹³CO₂ was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5–3.0 per mil (‰) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, 100% and 94.1%, respectively. In conclusion, ¹³C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific ¹³C-UBT results.     

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.     

Diagnosis of lactose intolerance and the “nocebo” effect: The role of negative expectations

BackgroundDiagnosis of lactose intolerance is based on a “positive” H₂ breath test associated with abdominal symptoms. The present study established to what extent the occurrence of symptoms during a “negative” H₂ breath test may result from a “nocebo effect” instead of lack of sensitivity of the procedure.MethodsBetween 2005 and 2007, 636 outpatients performed a standard 4-h 25 g lactose tolerance test. The test was positive in 254, negative in 325, and 57 patients were H₂ “non-producers”. Twenty-seven patients reporting symptoms despite a negative H₂ breath test underwent a “sham” breath test following ingestion of 1 g of glucose. Fifty-four patients presenting with documented lactose intolerance were used as controls.ResultsTwelve out of 27 patients (44.4%), and unexpectedly also 14 (25.9%) controls presented abdominal symptoms during the sham test. The difference between the two groups was not significant (P < 0.15) OR 2.28; C.I. 0.77–6.78.ConclusionIn most instances, symptoms reported by patients during a negative lactose H₂BT cannot be attributed to a false-negative test. Instead, a non-organic component, resulting from negative expectations (“nocebo effect”) is likely implicated. Moreover, also in patients diagnosed as lactose intolerant, the need for restricting the primary source of dietary calcium should be critically reconsidered.     

Relationship between methane production and breath hydrogen excretion in lactose-malabsorbing individuals

Recent studies have shown reduced breath hydrogen (H₂) excretion in methane (CH₄)-producing healthy individuals following ingestion of lactulose. This questions the reliability of the breath hydrogen test (BHT) in CH₄ excretors, but the relationship between CH₄ and H₂ excretion in other clinical applications of the BHT is not known. We reviewed BHT results in two groups of subjects: (1) 385 children tested for lactose malabsorption in a hospital setting, and (2) 109 lactose-malabsorbing patients tested with a home kit. The percentage of lactose malabsorbers in group 1 (51%) was the same regardless of CH₄-producing status (P=0.97). The BHT data from group 2 showed a positive correlation (r=0.6, P<0.000001) between the magnitude of the rise in CH₄ and H₂ concentrations, and the H₂ excretion curves were significantly higher in the CH₄-producing individuals. We conclude that attention to CH₄-producing status is not necessary in the interpretation of the lactose BHT.     

Determination of DLCO and cardiac output from expired gas slopes with cardiogenic oscillations

Effects of ‘cardiogenic oscillations’ on alveolar plateau gas concentration slope measurements, constant expiratory pulmonary capillary blood flow, and Dl_CO determination have not been previously described. We examined cardiogenic oscillations during constant expiratory maneuvers to assess factors influencing magnitude of oscillations as well as effect of oscillatory phase at the start and end of exhalation measurement period on alveolar gas slope. Five normal volunteers performed repeated single breath constant exhalation vital capacity maneuvers using test gas containing 2 physiologically ‘inert’ gases: Helium (He M_w 4) and argon (Ar M_w 40). The mixture contained 3 absorbable gases, acetylene (C₂H₂M_w 26), carbon monoxide (C¹⁸O M_w 30), and oxygen. Alveolar plateau slope, magnitude of cardiogenic oscillations, relative signal to noise ratios, and effect of cardiogenic oscillation phase on measured slope were determined for each gas. Cardiogenic oscillations were present for all inert gases. Oscillations were less evident for CO. However, the effects on calculated Q̇c and Dl_CO were negligible. cardiac oscillations of considerable magnitude are seen during single breath constant exhalation maneuvers and affect constant expiratory gas slope calculations. Cardiogenic oscillation phase does not have a significant effect on measured Q̇c and Dl_CO using constant expiratory techniques.