Breath Test Measurements Research Articles

Effect of Helicobacter pylori infection on body fat percentage in middle-aged and elderly populations

BackgroundObesity, which is associated with excessive accumulation of body fat, is emerging as a new public health problem. Bioelectrical impedance analysis (BIA) is a non-invasive and straightforward method to analyze body composition, providing a more accurate estimate of obesity than the commonly used body mass index. The primary objective of this study was to examine the potential impact of Helicobacter pylori (H. pylori) infection on body fat percentage in a population using cross-sectional and cohort studies. Methods: A population of people who underwent physical examinations at Taizhou Hospital between 2017 and 2022 was included. The participants underwent various tests, including urea breath test, hematological examination, and anthropometric measurement, in addition, their body fat percentage was determined through the use of BIA. Univariate and multifactorial regression analyses were conducted to identify factors associated with excess body fat. Results: There was a difference in body fat percentage between H. pylori positive and negative populations. The population was divided into young and middle-aged and elderly according to age, and H. pylori infection was found to differ only in the middle-aged and elderly population. Multifactorial logistic regression showed that H. pylori infection remained associated with excess body fat in the middle-aged and elderly population. A subsequent cohort study confirmed the association of persistent H. pylori infection with excess body fat in the population. Conclusion: H. pylori was negatively associated with excess body fat in middle-aged and elderly populations, and long-term H. pylori infection has a negative effect on body fat in people.

Relationship between Helicobacter pylori and glycated hemoglobin: a cohort study.

Helicobacter pylori (H. pylori) has increasingly been shown to be related to extragastric diseases. Glycated hemoglobin A1c (HbA1c), an indicator of glycemic control, is closely linked to the event of diabetes. The purpose of this research was to analyze the association between H. pylori and HbA1c through a cohort study. The population who underwent multiple physical checkups in the physical examination center of Taizhou Hospital was included. All of them underwent urea breath test, serological examination and physical parameter measurement. Multiple regression was used for analyzing the influencing factors of HbA1c. In addition, the result of HbA1c on H. pylori infection was studied by restricted cubic spline (RCS) analysis. The triglyceride glucose (TyG) index represents the level of insulin resistance (IR) in the population. The population was classified on the basis of primary and last H. pylori infection, therefore, the variations of HbA1c and TyG index among totally different teams were investigated. Multiple regression demonstrated that H. pylori was an influential factor in HbA1c. RCS analysis showed a nonlinear relationship between HbA1c and H. pylori infection. When HbA1c>5.7%, the chance of H. pylori infection was considerably enlarged. Additionally, long-term H. pylori infection increased HbA1c levels, while HbA1c levels decreased after H. pylori eradication. Similarly, long-term H. pylori infection also increased the TyG index. Prediabetes increases the danger of H. pylori infection, long-term H. pylori infection increases HbA1c and IR levels, and wipeout of H. pylori could have a positive impact for glycemic control in the population.

S1582 Abnormal Glucose Breath Test Does Not Correlate With Patient’s Self-Reported Symptoms and Their Severity

Introduction: Glucose Hydrogen Breath Testing (GBT) is commonly used for diagnosing Small Intestinal Bacterial Overgrowth (SIBO). However, patients present with clinical symptoms (sx) and their predictive value for a positive (pos) GBT remains unclear. AIM: To assess the prevalence of self-reported GI sx profiles in adults with unexplained upper GI symptoms and correlate this with GBT. Methods: We retrospectively analyzed all adult patients presenting to a single medical center from 6/20 –12/21 for GBT. A pos GBT for SIBO was defined by the North American Consensus (≥20 ppm H2 increase over basal within 90 minutes (mins) and/or ≥10 ppm CH4 at any time). Pts completed a GI questionnaire assessing 17 key sxs: regurgitation (RG), chest pain (CP), heartburn (HB), belch (BH), abdominal pain (AP), bloating (BT), gas (GS), nausea (NA), vomit (VT), abdominal cramps (AC), indigestion (ID), distension (DN), fullness (FL), early satiety (ES), diarrhea (DR), constipation (CN), and fatigue (FT). Sxs measured by frequency (None, < 1/week (wk), 1/wk, ≥ 1/wk), intensity (None, Mild, Moderate, Severe), and duration (None, < 10 mins, 10 – 30 mins, ≥ 30 mins). Sub-groups, GERD, Dyspeptic, and IBS were constructed assessing the mean summation scores for Frequency, Intensity, and Duration between negative (neg) and pos GBTs. Univariate analysis and logistic regression analysis was performed. A P-value of < 0.05 was considered statistically significant. Results: We evaluated 184 pts, mean age of 51.7 (18 – 85), 78.3% female, 82.8% Caucasian, and mean BMI of 27.2. No significant differences were seen between GI sx frequency and intensity categories for pts with GBT neg and pos groups. A trend for a higher percentage of pos GBT pts reporting FL (P=0.09) and DR (P=0.07) in sx duration categories of 10 -30 mins (FL: 30.8% vs 27.5%; DR: 31.8% vs 23.4%) and ≥ 30 mins (FL: 51.3% vs 41.3%; DR: 37.2% vs 22.1%) was noted. Regression analysis showed a trend toward a pos GBT for VT frequency of Less than 1/wk: (P = 0.07; OR = 2.99; 95% CI: 0.91, 9.83) and NA intensity of Severe: (P = 0.09; OR = 2.24; 95% CI: 0.86, 5.84). No differences were seen between the GERD, Dyspeptic, and IBS sub-groups (Figure). Conclusion: The pre-test predictability of GI symptoms as it relates to a pos or neg GBT is poor. The yield for a pos GBT varies between 31%-55% and depends on age. In routine practice, when the index of clinical suspicion is high for SIBO, clinicians should consider objective testing with GBT rather than empiric antibiotic treatment.Figure 1.: (Left) Mean Summation Scores for Self-Reported Frequency, Intensity, and Duration Responses to GI Symptoms Relative to the Gastroesophageal Reflux Disease (GERD), Dyspeptic, and irritable bowel syndrome (IBS) Groups. (Right) Prevalence of Positive Glucose Breath Test (GBT) Among Age Cohorts and Glucose Breath Test Measurements

The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that “low-viscosity” soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

Enzymatic liver function measured by LiMAx is superior to current standard methods in predicting transplant-free survival after TIPS implantation

Transjugular intrahepatic portosystemic shunt (TIPS) is one of the main treatment options in patients with decompensated liver cirrhosis but is still associated with partly severe complications. For adequate patient selection, prognostic parameters are of crucial importance. The liver maximum capacity (LiMAx) breath test measures enzymatic liver function and could potentially represent an efficient prognostic marker. We therefore aimed to assess the role of LiMAx in predicting survival of TIPS patients in a prospective analysis. LiMAx was performed for patients who underwent TIPS implantation between October 2016 and February 2018. Associations with transplant-free survival after 24 weeks were assessed by logistic regression. A total number of 30 patients were included, of whom seven received liver transplantation (N = 2) or died (N = 5) during follow-up. LiMAx values after (P = 0.01, OR = 1.24, 95% CI = 1.04–1.47) and before (P = 0.03, OR 1.21, 95% CI = 1.02–1.43) TIPS implantation and MELD score (P = 0.03, OR = 0.79, 95% CI = 0.63–0.98) were significantly associated with transplant-free survival according to univariate logistic regression. In AUROC analysis, LiMAx at day one after TIPS (sensitivity 85.7%, specificity 78.3%, AUROC 0.85, cut-off ≤ 165 µg/kg/h), LiMAx value at the day before TIPS (sensitivity 100%, specificity 73.9%, AUROC 0.82, cut-off ≤ 205 µg/kg/h) and MELD score (sensitivity 71.4%, specificity 73.9%, AUROC 0.82, cut-off ≥ 15) had the highest prognostic accuracy. LiMAx values prior and after TIPS procedure seem to be good prognostic parameters regarding prediction of transplant-free survival of patients undergoing TIPS implantation.

The alcohol breath test in practice: effects of exhaled volume.

Alcohol breath test (ABT) measurements are sensitive to the volume of the exhaled breath. Although a minimum breath volume is required for a legally acceptable sample, any additional increase in the volume of exhaled air increases the measurement of breath alcohol concentration (BrAC). Using a sample of 115 ABTs collected by police agencies for evidentiary purposes, we studied the influence of exhaled air volume on the measurement of BrAC. The 115 ABTs were performed on 30 different Alcotest 9510s. Each of the tests included paired, time series measurements of exhaled breath flow rates and breath alcohol content. The exhalation flow rates and exhalation times were used to create exhalation volume-BrAC plots. On average, exhaled air volumes were ~50% of the subjects' age-, height-, race-, and sex-predicted vital capacities (VC). More than 80% of the samples had exhaled air volumes ranging between 30 and 70% of the subject's predicted VC. Breath volumes for duplicate breath samples were similar. For all breath samples, BrAC increased with exhalation volume, an expected behavior for any very high blood solubility compound such as alcohol. Beyond the legally accepted minimum expiratory volume, BrAC increased, on average, at a rate of 9.2 ± 2.8%/liter air exhaled. As a result, a person who exhales just beyond the minimum volume will have a lower BrAC compared with a person who exhales a full VC. Exhaled volume materially impacts the measurement of an ABT. NEW & NOTEWORTHY Subjects who provide breath samples for evidentiary alcohol breath tests exhale, on average, about half of their predicted vital capacity. Because breath alcohol concentration increases with greater exhaled air volume, subjects who exhale more than average volume will have a greater breath alcohol concentration, whereas subjects who exhale less than average volume will have a lesser breath alcohol concentration. A quantification of air volume impact on breath alcohol concentration is provided.

Helicobacter pylori infection is not related to increased carotid intima-media thickness in general population

The aim is to determine whether there is an independent association between Hp infection and carotid intima-media thickness (CIMT) in a cross-section observational study. Among of 14588 routine health check-up participants, 13770 subjects underwent the 13C-urea breath test (13C-UBT) and ultrasound measurement of CIMT. Traditional atherosclerotic risk factors were also recorded. The ratio of increased CIMT in Hp positive group (28.6%) was not significant difference compared with Hp negative group (29.7%) (p = 0.164). The HP infection rates was no significant difference between increased CIMT (38.4%) and non- increased CIMT (39.7%) patients. However, all the traditional atherosclerotic risk factors including age, gender, BMI, waistline, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, free fatty acid, homocysteine, systolic and diastolic blood pressure, fasting plasma glucose and C reactive protein were different between increased CIMT and non- increased CIMT participants. The odds of Hp infection for CIMT risk (OR 0.948; 95% CI 0.879–1.022; P = 0.164) was not higher in binary logistic regression analysis even after adjustment for traditional risk factors (OR 1.118; 95% CI 0.958–1.306; P = 0.157). Our study found no evidence of association between CIMT and HP infection.

The Predictive Value of the Hydrogen Breath Test in the Diagnosis of Fructose Malabsorption

Background: Fructose malabsorption is commonly diagnosed by the hydrogen fructose (H₂) breath test. However, the mechanisms behind fructose malabsorption in humans are not well understood and the clinical relevance of this test is considered controversial. Hence, the main aim of this study is to evaluate the predictive value of the H₂ breath test. Methods: Regarding exclusion criteria, the study enrolled 562 consecutive patients, enlisted to a gastroenterology clinic between 2009 and 2011 for testing malabsorption. In the final data analysis, 246 patients were included. Ecotrophologists used 3 categories to rate dietary success: complete response, partial response and no response to the diet. They also rated the occurrence of abdominal pain, diarrhoea and bloating during the H₂ breath test. Ordinal regression analysis using SPSS was performed to evaluate whether H₂ breath test results – measured as the maximum H₂ level, the maximum increase in H₂, and the area under the curve (AUC) – predicted dietary success or failure. Correlation analyses were applied to test whether symptoms of fructose malabsorption correlated with the H₂ breath test measures. Finally, we evaluated whether cut-off-values of 40 or 60 parts per million (ppm) serve better than the test measure of 20 ppm to diagnose fructose malabsorption. Results: When a fructose-free diet was administered it was found that 103 patients (41.9%) were complete responders, 116 (47.2%) were partial responders and 27 (11%) were non-responders. The H₂ breath test with the 20 ppm cut-off-value, that is, the maximum H₂ level, the maximum increase in H₂, and the AUC did not predict dietary response (all 95% CI ns). This was also the case when using 40 or 60 ppm as cut-off-values (all 95% CI ns). Abdominal pain during the test correlated significantly with the AUC. Diarrhoea and bloating correlated significantly with the AUC, the maximum H₂ level and the maximum increase in H₂ (p < 0.05). Conclusions: The H₂ breath test produced no predictive value for the fructose-free diet outcomes; its value as a predictive test is therefore questionable. However, the symptoms of fructose malabsorption correlated significantly with the H₂ breath test measures, and this is an indication that there is at least a degree of validity of the H2 breath test beyond the simple detection or exclusion of fructose malabsorption.

The safety and sensitivity of a telemetric capsule to monitor gastrointestinal hydrogen production invivo in healthy subjects: a pilot trial comparison to concurrent breath analysis.

Intestinal gases are currently used for the diagnosis of disorders including small intestinal bacterial overgrowth and carbohydrate malabsorption. To compare the performance of measuring hydrogen production within the gut directly with the telemetric gas-sensing capsule with that of indirect measurement through breath testing. Using standard breath testing protocols, the capsules and breath tests were simultaneously evaluated in a single-blinded trial in 12 healthy subjects. Eight received a single dose of 1.25-40g inulin and four 20 or 40g glucose. Safety and reliability of the capsules were also assessed. There were no reported adverse events. All capsules were retrieved and operated without failure. Capsule measurements were in agreement with breath test measurements in magnitude but not in timing; minimal hydrogen production was observed after glucose ingestion and capsule measurements correlated with breath hydrogen after ingestion of 40g inulin. A dose-dependent increase in concentration of hydrogen was observed from the capsule following ingestion of inulin as low as 1.25g compared with >10g for breath measurements. Specifically, the capsule measured >3000 times higher concentrations of hydrogen compared to breath tests, resulting in a signal-to-noise ratio of 23.4 for the capsule compared to 4.2 for the breath test. The capsule showed high sensitivity and signal-to-noise ratio in measuring luminal hydrogen concentrations, provided information on the site of intestinal gas production, and demonstrated safety and reliability. The capsule has potential for improving diagnostic precision for disorders such as small intestinal bacterial overgrowth.

Issue Highlights

Issue Highlights

Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load

ObjectiveTo evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. MethodsNon-obese, obese normoglycemic and obese type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. ResultsBreath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. ConclusionsAugmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes.

Mixture randomized item‐response modeling: a smoking behavior validation study

Misleading response behavior is expected in medical settings where incriminating behavior is negatively related to the recovery from a disease. In the present study, lung patients feel social and professional pressure concerning smoking and experience questions about smoking behavior as sensitive and tend to conceal embarrassing or threatening information. The randomized item-response survey method is expected to improve the accuracy of self-reports as individual item responses are masked and only randomized item responses are observed. We explored the validation of the randomized item-response technique in a unique experimental study. Therefore, we administered a new multi-item measure assessing smoking behavior by using a treatment-control design (randomized response (RR) or direct questioning). After the questionnaire, we administered a breath test by using a carbon monoxide (CO) monitor to determine the smoking status of the patient. We used the response data to measure the individual smoking behavior by using a mixture item-response model. It is shown that the detected smokers scored significantly higher in the RR condition compared with the directly questioned condition. We proposed a Bayesian latent variable framework to evaluate the diagnostic test accuracy of the questionnaire using the randomized-response technique, which is based on the posterior densities of the subject's smoking behavior scores together with the breath test measurements. For different diagnostic test thresholds, we obtained moderate posterior mean estimates of sensitivity and specificity by observing a limited number of discrete randomized item responses.

Could Carbon Breath Test Measurement Accurately Reflect Gastric Emptying of Liquid Nutrient Meal in the Critically Ill Patients? (Gut 2011;60:1336-1343)

It is assumed that delayed gastric emptying (GE) occurs frequently in critically ill patents, but the overall prevalence of delayed GE in these patients using scintigraphy remains uncertain. Recently Chapman et al1 reported that GE was demonstrated to be slow in about 50% of intensive care unit patient using scintigraphy and the breath test appears to be an accurate alternative to scintigraphy for the measurement of GE in critically ill patients. Studies were performed in the 25 unselected, mechanically ventilated patients and 14 healthy controls. A nasogastric (NG) tube was inserted to all of healthy controls for the purpose of the study and its position was verified by pH measurement of NG tube aspirates. Prior to the study, the gastric contents were aspirated and a test meal which consisted of 100 mL Ensure (1 kcal/mL) doped with 20 MBq 99mTechnetium sulphur colloid and 75 KBq octanoic acid, [1-14C] sodium salt was infused into the stomach via the NG tube over 5 minutes. The scintigraphic measurement of GE was performed in patients and healthy controls using a mobile γ camera with 3 minute dynamic frame acquisition. Gastric meal retention (scintigraphy) at 60, 120, 180 and 240 minutes, breath test t50 (BT50) and GE coefficient were determined. Before and after the study, the gastric residual volume (GRV) was determined every 6 hour and the total volumes were documented for 24 hour preceding the study. The authors demonstrated that, of the 24 patients with scintigraphy data, GE was delayed at 120 minutes in about 50% of intensive care unit patients. Patients with delayed GE had greater severity of illness on admission to the intensive care unit, and were more likely to have been admitted with trauma, sepsis and respiratory failure. Breath tests correlated well with scintigraphy in both patients and healthy controls (% retention at 120 minutes vs BTt50; r2 = 0.57 healthy; r2 = 0.56 patients; P ≤ 0.002 for both). There was also a strong correlation between breath measurements and intragastric retention in both patients and healthy controls. In patients with slow GE there was a trend for a reduced volume nutrient delivery, and energy delivery was reduced in the patients with slow GE (normal GE 1,920 vs slow GE 510 kcal; P = 0.047). Therefore, they concluded that GE was delayed in about half of critically ill patients and markedly delayed in about 20%, and breath tests correlated well with scintigraphy and could be used as a valid method for the measurement of GE in these patients for research purposes to quantify the effects of promotility agents.

Gastric emptying of a liquid nutrient meal in the critically ill: relationship between scintigraphic and carbon breath test measurement

ObjectiveIt is assumed that delayed gastric emptying (GE) occurs frequently in critical illness; however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could...

Efficacy of Korean Red Ginseng Supplementation on Eradication Rate and Gastric Volatile Sulfur Compound Levels after Helicobacter pylori Eradication Therapy

This clinical study was performed to evaluate whether supplementation of proton pump inhibitor (PPI)-based triple therapy with Korean red ginseng can enhance Helicobacter pylori (H. pylori) eradication and reduce levels of halitosis-associated volatile sulfur compounds (VSCs) in the stomach. Seventy-six patients were randomized into an eradication regimen-only group (n=45) or an eradication regimen plus 10 weeks of Korean red ginseng supplementation group (n=31). The eradication regimen consisted of PPI b.i.d., clarithromycin 500 ㎎ b.i.d., and amoxicillin 1 g b.i.d.. for seven days. Korean red ginseng supplementation commenced on the last day of the eradication regimen. ¹³C-urea breath test and halimeter measurements were performed prior to protocol repetition. By intention-to-treat analysis, the H. pylori eradication rate in the Korean red ginseng group (77.4%, 24 of 31) was higher than that in the control group (45.0%, 26 of 45). However, by per protocol analysis, the eradication rate in the Korean red ginseng group was significantly higher than that in the control group (92.3%, 24/26 vs. 69.4%, 26/38; p＜0.05). H. pylori infection was significantly associated with increased VSC levels. However, VSC levels decreased significantly in the Korean red ginseng group (p＜0.05). In conclusion, supplementation of triple therapy with Korean red ginseng increased the H. pylori eradication rate and led to significant reductions in VSC levels, suggesting the usefulness of this substance in combating H. pylori infection.

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

There is no generally accepted kinetic evaluation method for the stable isotope [(13)C]ketoisocaproic acid (KIC) breath test. Differences found in the results between women and men are contradictory. 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 (13)CO(2) 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. 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. 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.

Effects of postgastric13C-acetate processing on measurement of gastric emptying: a systematic investigation in health

Uniform postgastric processing of the gastric emptying (GE) marker 13C-acetate (Ac) is an unverified assumption behind its widespread application to measure GE. This study assessed the postgastric processing of Ac administered by intraduodenal (i.d.) infusion simulating different physiological conditions. 13CO2 in breath was assessed in three groups of six volunteers after i.d. administration of A: Different caloric densities (0.75/1.5/3 kcal min(-1) in a 200 mL meal at constant 1 mg Ac min(-1) simulating a physiological range of nutrient delivery rates; B: different tracer delivery rates (0.5/1.0/2.5 mg Ac min(-1) simulating delayed, normal and increased GE; C1: a 500 mL meal resulting in same marker and caloric delivery compared to protocol A; C2: 50 mL water bolus injections of 12.5/25/50/100 mg Ac and C3 bolus injections of 50 mg Ac in 50/100/200 mL water in randomized order. A: 13CO2 excretion was independent of caloric load (P = 0.59). B: The dynamic of 13CO2 excretion was modulated by tracer elimination which was in turn dependent on the speed of tracer delivery, i.e. with faster deliveries resulting in lower 13CO2 recovery during infusion (P < 0.001). C: Increasing Ac doses resulted in decreased 13CO2 recovery (P < 0.001) over the first hour. 13CO2 recovery kinetics was independent of the volume delivered. This study shows 13C-acetate absorption and metabolism is independent of the volume and caloric delivery of test meals. The 'lag' in estimates of GE derived from 13CO2 breath tests is due to a postgastric, dose-dependent delay to 13CO2 elimination. This can be corrected for in analytical derivations of GE parameters based on 13C-acetate breath test measurements.

Halofuginone can worsen liver fibrosis in bile duct obstructed rats.

Halofuginone (HF) is an antifibrotic agent in rat models of liver fibrosis caused by repetitive intoxications. A beneficial effect of HF on a biliary type of liver fibrosis has not been proven yet. Bile duct-obstructed rats were given HF from the moment of obstruction onwards and compared with no treatment. After 3 weeks, respectively, 6 weeks, aminopyrine breath test (ABT) and haemodynamic measurements including of portal pressure were carried out. Liver pieces were taken for Sirius red quantitative scoring, as well as for semiquantitative determinations of collagen type I and III RNA levels. ABT was significantly worse in HF-treated rats as compared with no treatment (P=0.02). Haemodynamic data and collagen type I and III determinations were not significantly different between groups. Biliary fibrosis scores were significantly higher in HF-treated rats as compared with no treatment (P=0.03). More Sirius red staining was associated with more proliferation of bile ductules. HF may worsen biliary fibrosis. This contrasts sharply with antifibrotic effects in other models of liver fibrosis. Distinctive cellular mechanisms in biliary fibrosis may explain this discrepancy. One should be cautious for chronic application of HF in man with cholestasis.

Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test.

The aim of the present study was to develop a test for measuring hepatic and intestinal removal of cytochrome p-450 3A4 (CYP3A4)- and P-glycoprotein (PGP)-dependent xenobiotics that would be applicable for clinical use in humans. Orally and intravenously administered [N-methyl-14C]erythromycin was used for evaluation of 14C-labeled excretion dynamics in breath and urine. Simultaneous breath and urine test measurements were performed in 32 healthy volunteers and in 23 renal transplant recipients. Mathematical analysis of the excretion rate of labeled CO2 in breath and labeled carbon in urine resulted in 1). separation of both CYP3A4 and PGP activity in the liver and the intestinal mucosa and 2). numerical calculation of the dynamics of the different processes. The test was sufficiently sensitive to detect theoretically predicted process-specific pharmacological modulations by different drugs in healthy volunteers and after recent renal transplantation. It is concluded that the combined oral and intravenous erythromycin breath and urine test is a reliable and noninvasive test to measure phenotypic intestinal and hepatic CYP3A4 and PGP activity and may be a promising tool for prediction of drug interactions and dose adjustment of many pharmacotherapeutics in clinical practice, e.g., immunosuppressive agents after renal transplantation.

Troglitazone induces CYP3A4 activity leading to falsely abnormal dexamethasone suppression test.

After evaluating a patient who appeared to have a falsely abnormal response to the dexamethasone suppression test while taking troglitazone, we examined the effects of troglitazone on the activity of hepatic CYP3A4 and the screening tests for Cushing's syndrome. We studied five healthy women and three healthy men, aged 25 +/- 2 yr, before and after treatment with troglitazone (600 mg daily) for 28 d. Baseline 0800 h cortisol and corticosterone were similar before and after troglitazone treatment. Before troglitazone treatment, all subjects suppressed 0800 h cortisol below 1.8 micro g/dl (mean, 0.66 +/- 0.08 micro g/dl) during the 1-mg overnight dexamethasone suppression test (DST), whereas during troglitazone treatment none of the subjects suppressed 0800 h cortisol below 1.8 micro g/dl (mean, 9.0 +/- 1.8 micro g/dl). Serum dexamethasone levels decreased by 66 +/- 4%, and the erythromycin breath test measurements increased by 27 +/- 8%, indicating increased CYP3A4 activity during troglitazone treatment. The hydrocortisone suppression test (HST) was performed by administering 50 mg hydrocortisone at 2300 h. Using the criterion of suppression of 0800 h plasma corticosterone by more than 50%, the specificity of the HST was 100% both before and after troglitazone treatment. In conclusion, troglitazone induced the activity of CYP3A4 leading to falsely abnormal DST. HST is a useful alternative to the DST in patients taking medications that increase the activity of CYP3A4.