Showing papers on "Breath test published in 2019"

Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis

Abstract: Background The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial. Objective To assess association between gastric emptying and UGI Sx, independent of treatment. Design We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests. Results Systematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2 ) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis. Conclusions The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

Accuracy and Methodologic Challenges of Volatile Organic Compound–Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis

Abstract: Importance The detection and quantification of volatile organic compounds (VOCs) within exhaled breath have evolved gradually for the diagnosis of cancer. The overall diagnostic accuracy of proposed tests remains unknown. Objectives To determine the diagnostic accuracy of VOC breath tests for the detection of cancer and to review sources of methodologic variability. Data Sources An electronic search (title and abstract) was performed using the Embase and MEDLINE databases (January 1, 2000, to May 28, 2017) through the OVID platform. The search terms cancer , neoplasm , malignancy , volatile organic compound , VOC , breath , and exhaled were used in combination with the Boolean operators AND and OR. A separate MEDLINE search that used the search terms breath AND methodology was also performed for studies that reported factors that influenced the concentration of VOCs within exhaled breath in humans. Study Selection The search was limited to human studies published in the English language. Trials that analyzed named endogenous VOCs within exhaled breath to diagnose or assess cancer were included in this review. Data Extraction and Synthesis Systematic review and pooled analysis were conducted in accordance with the recommendations of the Cochrane Library and Meta-analysis of Observational Studies in Epidemiology guidelines. Bivariate meta-analyses were performed to generate pooled point estimates of the hierarchal summary receiver operating characteristic curve of breath VOC analysis. Included studies were assessed according to the Standards for Reporting of Diagnostic Accuracy Studies checklist and Quality Assessment of Diagnostic Accuracy Studies 2 tool. Main Outcomes and Measures The principal outcome measure was pooled diagnostic accuracy of published VOC breath tests for cancer. Results The review identified 63 relevant publications and 3554 patients. All reports constituted phase 1 biomarker studies. Pooled analysis of findings found a mean (SE) area under the receiver operating characteristic analysis curve of 0.94 (0.01), sensitivity of 79% (95% CI, 77%-81%), and specificity of 89% (95% CI, 88%-90%). Factors that may influence variability in test results included breath collection method, patient physiologic condition, test environment, and method of analysis. Conclusions and Relevance The findings of our review suggest that standardization of breath collection methods and masked validation of breath test accuracy for cancer diagnosis is needed among the intended population in multicenter clinical trials. We propose a framework to guide the conduct of future breath tests in cancer studies.

Blood Ketone Bodies and Breath Acetone Analysis and Their Correlations in Type 2 Diabetes Mellitus.

Abstract: Analysis of volatile organic compounds in the breath for disease detection and monitoring has gained momentum and clinical significance due to its rapid test results and non-invasiveness, especially for diabetes mellitus (DM). Studies have suggested that breath gases, including acetone, may be related to simultaneous blood glucose (BG) and blood ketone levels in adults with types 2 and 1 diabetes. Detecting altered concentrations of ketones in the breath, blood and urine may be crucial for the diagnosis and monitoring of diabetes mellitus. This study assesses the efficacy of a simple breath test as a non-invasive means of diabetes monitoring in adults with type 2 diabetes mellitus. Human breath samples were collected in Tedlar™ bags and analyzed by headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). The measurements were compared with capillary BG and blood ketone levels (β-hydroxybutyrate and acetoacetate) taken at the same time on a single visit to a routine hospital clinic in 30 subjects with type 2 diabetes and 28 control volunteers. Ketone bodies of diabetic subjects showed a significant increase when compared to the control subjects; however, the ketone levels were was controlled in both diabetic and non-diabetic volunteers. Worthy of note, a statistically significant relationship was found between breath acetone and blood acetoacetate (R = 0.89) and between breath acetone and β-hydroxybutyrate (R = 0.82).

The potential of breath analysis to improve outcome for patients with lung cancer

Abstract: Lung cancer remains the most common cause of cancer related death in both the UK and USA. Development of diagnostic approaches that have the ability to detect lung cancer early are a research priority with potential to improve survival. Analysis of exhaled breath metabolites, or volatile organic compounds (VOCs) is an area of considerable interest as it could fulfil such requirements. Numerous studies have shown that VOC profiles are different in the breath of patients with lung cancer compared to healthy individuals or those with non-malignant lung diseases. This review provides a scientific and clinical assessment of the potential value of a breath test in lung cancer. It discusses the current understanding of metabolic pathways that contribute to exhaled VOC production in lung cancer and reviews the research conducted to date. Finally, we highlight important areas for future research and discuss how a breath test could be incorporated into various clinical pathways.

Sensitivity and specificity of an electronic nose in diagnosing pulmonary tuberculosis among patients with suspected tuberculosis

Abstract: OBJECTIVE: To investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB. METHODS: Setting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5-2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum's Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum's ROC-curve. Differences between Area-under-the-Curve between strata (p<0.05) indicated an association between the variable and sensitivity-specificity of the breath test. Statistical analysis was performed using STATA/SE 15. RESULTS: Of 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75-92%) and 78% (95%CI: 70-85%), specificity was 55% (95%CI: 44-65%) and 42% (95%CI: 34-50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men. CONCLUSION: The electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings.

Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer.

Abstract: A noninvasive breath test has the potential to improve survival from esophagogastric cancer by facilitating earlier detection. This study aimed to investigate the production of target volatile fatty acids (VFAs) in esophagogastric cancer through analysis of the ex vivo headspace above underivatized tissues and in vivo analysis within defined anatomical compartments, including analysis of mixed breath, isolated bronchial breath, and gastric-endoluminal air. VFAs were measured by PTR-ToF-MS and GC-MS. Levels of VFAs (acetic, butyric, pentanoic, and hexanoic acids) and acetone were elevated in ex vivo experiments in the headspace above esophagogastric cancer compared with the levels in samples from control subjects with morphologically normal and benign conditions of the upper gastrointestinal tract. In 25 patients with esophagogastric cancer and 20 control subjects, receiver-operating-characteristic analysis for the cancer-specific VFAs butyric acid (P < 0.001) and pentatonic acid (P = 0.005) within in vivo...

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

Abstract: 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.

Repeatability and effect of blinding of fructose breath tests in patients with functional gastrointestinal disorders.

Abstract: Background Breath tests are used as measures of sugar intolerance or malabsorption in patients with functional gastrointestinal disorders (FGID), although the repeatability or anticipatory bias have not been adequately studied. We examined the repeatability and anticipatory bias during fructose breath testing using a nocebo-controlled, randomized, cross-over, and double-blind study design. Methods Gastrointestinal symptoms and breath concentrations of hydrogen and methane were documented during breath tests with fructose (given open twice and blinded once), water (blind neutral nocebo) and a cyclamate/saccharine sweetener (blind sweet nocebo) on 5 days in patients with FGID. Repeatability of fructose breath tests (16 patients) and differences between open and blinded substrate groups (31 patients) was assessed using thresholds for intolerance and malabsorption, and areas-under-the-curve (AUC) of symptoms and breath gas concentrations. Key results Fructose breath tests showed moderate repeatability for intolerance status (absolute agreement 87%, kappa 0.72), but limited repeatability for malabsorber status (absolute agreement 53%, kappa 0.05). Repeatability of AUCs of GI symptoms, hydrogen and methane breath concentrations was moderate (intraclass correlation coefficients 0.70, 0.57, and 0.57, respectively). There were no significant differences between open and blinded fructose breath tests in intolerance or malabsorber status, or in AUCs of GI symptoms, hydrogen and methane concentrations. Conclusions & inferences Fructose breath tests showed moderate repeatability for intolerance status and for AUCs of symptoms and gas concentrations, lying within the range of accepted gastrointestinal sensory and transit tests. Repeatability for malabsorption status was inadequate and requires revisiting. The fructose breath test can be used unblinded in FGID.

Prevalence and associated factors of small intestinal bacterial overgrowth among systemic sclerosis patients.

Abstract: Background Small intestinal bacterial overgrowth (SIBO) results in nutrient malabsorption and malnutrition, thereby increasing the morbidity and mortality in systemic sclerosis (SSc) patients. Objectives To evaluate the prevalence and associated factors of SIBO in SSc patients. Method A cross-sectional study was conducted between July 2015 and January 2016 in SSc patients over 18, using the glucose H2 /CH4 breath test to evaluate SIBO. Results Eighty-nine SSc patients (30 male and 59 female) underwent the glucose H2 /CH4 breath test. The mean age was 54.4. Twelve participants were positive for the glucose H2 /CH4 breath test, yielding a SIBO prevalence of 13.5% (95% CI 7.2-22.4) among SSc patients. A multivariate analysis revealed that duration of disease >5 years was significantly associated with SIBO (adjusted odds ratio 9.38; 95% CI 1.09-80.47). Conclusion The prevalence of SIBO, using the glucose H2 /CH4 breath test, is not common among Thai SSc patients. However, a positive result was associated with longer duration of disease.

The Use of Selected Ion Flow Tube-Mass Spectrometry Technology to Identify Breath Volatile Organic Compounds for the Detection of Head and Neck Squamous Cell Carcinoma: A Pilot Study.

Abstract: Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide, with approximately 630,000 new cases diagnosed each year. The development of low-cost and non-invasive tools for the detection of HNSCC using volatile organic compounds (VOCs) in the breath could potentially improve patient care. The aim of this study was to investigate the feasibility of selected ion flow tube mass spectrometry (SIFT-MS) technology to identify breath VOCs for the detection of HNSCC. Materials and Methods: Breath samples were obtained from HNSCC patients (N = 23) and healthy volunteers (N = 21). Exhaled alveolar breath samples were collected into FlexFoil® PLUS (SKC Limited, Dorset, UK) sampling bags from newly diagnosed, histologically confirmed, untreated patients with HNSCC and from non-cancer participants. Breath samples were analyzed by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) (Syft Technologies, Christchurch, New Zealand) using Selective Ion Mode (SIM) scans that probed for 91 specific VOCs that had been previously reported as breath biomarkers of HNSCC and other malignancies. Results: Of the 91 compounds analyzed, the median concentration of hydrogen cyanide (HCN) was significantly higher in the HNSCC group (2.5 ppb, 1.6–4.4) compared to the non-cancer group (1.1 ppb, 0.9–1.3; Benjamini–Hochberg adjusted p < 0.05). A receiver operating curve (ROC) analysis showed an area under the curve (AUC) of 0.801 (95% CI, 0.65952–0.94296), suggesting moderate accuracy of HCN in distinguishing HNSCC from non-cancer individuals. There were no statistically significant differences in the concentrations of the other compounds of interest that were analyzed. Conclusions: This pilot study demonstrated the feasibility of SIFT-MS technology to identify VOCs for the detection of HNSCC.

Effect of Citric Acid on Accuracy of 13C-Urea Breath Test after Helicobacter pylori Eradication Therapy in a Region with a High Prevalence of Atrophic Gastritis.

Abstract: Background/Aims The validity of 13C-urea breath test (13C-UBT) for Helicobacter pylori detection is influenced by atrophic gastritis. The aim of this study was to evaluate the effect of citric acid on the accuracy of 13C-Urea breath test after H. pylori eradication therapy in a region where atrophic gastritis is common. Methods In this prospective study, H. pylori-positive patients received 13C-UBT after H. pylori eradication regimen. They were classified into citric acid group and control group. To determine diagnostic accuracy of 13C-UBT, patients were offered invasive methods. Results A total of 1,207 who successfully took H. pylori-eradication regimen received UBT. They were assigned into the citric acid group (n=562) and the control group (n=645). The mean 13C-UBT value of the citric acid group was 10.3±26.4‰, which was significantly (p<0.001) higher than that of that control group (5.1‰±12.6‰). Of these patients 122 patients were evaluated by endoscopic biopsy methods. Based on invasive tests, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 13C-UBT for the citric acid group were 83.3%, 91.7%, 81.3%, 55.0%, and 97.5%, respectively. Those of the control group were 87.7%, 90.9%, 88.2%, 62.5%, and 97.8%, respectively. They were not significantly different between the two groups. Although the presence of gastric atrophy and intestinal metaplasia (IM) decreased the accuracy, the decrease was not significant. Conclusions In a country with high prevalence of atrophic gastritis or IM, false positivity remained common despite the use of citric acid in 13C-UBT.

Reevaluating our understanding of lactulose breath tests by incorporating hydrogen sulfide measurements.

Abstract: Background and aim Breath testing has become a commonly used tool in gastroenterology to evaluate changes in the fermentation pattern of the gut microbiome. Currently, hydrogen and methane gas concentrations are measured in breath testing and evaluated against specific cut-off values for interpretation as normal or abnormal. However, microbial gas kinetics is a complex process that is not currently fully considered when interpreting breath gas results. Gas exchange between hydrogen producers and hydrogen consumers (methanogens and sulfate-reducing bacteria) is a process whereby hydrogen availability is determined by both its production and removal. Hydrogen sulfide is a crucial gas involved in this process as it is a major hydrogen-consumptive pathway involved in energy exchange. Methods This is a cross-sectional study evaluating lactulose breath testing with the inclusion of hydrogen sulfide measurements in patients referred for breath testing for gastrointestinal symptoms of bloating, excessive gas, and/or abdominal pain. Results A total of 159 patients were analyzed between October 2016 and June 2017. Mean hydrogen concentrations with a positive trend through a 3-h period (R 2 = 0.97), mean methane concentrations with a positive trend (R 2 = 0.69), and mean hydrogen sulfide concentrations with a negative trend (R 2 = -0.71) were observed. Conclusion By incorporating energy exchange in the interpretation of the lactulose breath test, we reevaluated specific breath gas profiles, including those commonly described as "hydrogen nonproducers" and the "double-peak" phenomenon.

Transcutaneous vagal nerve stimulation improves gastroenteric complaints in Parkinson's disease patients.

Abstract: Background Gastrointestinal dysfunctions are common in Parkinson's disease. Their management is still challenging and new treatment options are needed. Objective To test whether transcutaneous vagal nerve stimulation can improve gastrointestinal dysfunction in patients with Parkinson's disease. Methods We performed a randomized double-blind pilot study enrolling patients suffering from Parkinson's disease with gastroenteric complaints. Patients were randomized to use either a sham-device or to stimulate the vagal nerve with an electric device over the course of four weeks with four stimulations per day. Ten patients (aged 69.6±4.6 years) were randomized for the intervention group, and nine patients (aged 67.2±6.3 years) used a sham-device. Clinical outcome was evaluated using the Gastrointestinal Symptom Rating Scale whereas gastrointestinal motility was measured with the 13C-octanoic acid breath test. Results In the treatment group, vagal nerve stimulation improved the Gastrointestinal Symptom Rating Scale comparing before and after stimulation (before, 8.7±6.09; after 5.67±3.08; p-value 0.48). This improvement was not observed in the sham group (before, 7.44±4.85; after, 5.67±3.08; p-value 0.16). In the 13C-octanoic acid breath test no significant changes were detectable. Conclusions Vagal nerve stimulation is well tolerated with no side effects and may be a promising non-invasive therapy option to improve gastroenteric symptoms in Parkinson's disease.

Comparing radiopaque markers and 13 C-labelled breath test in diabetic gastroparesis diagnostics.

Abstract: Purpose: Determining gastric emptying is mandatory in the diagnosis of diabetic gastroparesis. Several methods of investigation exist, but none has proven reliable, inexpensive and accessible. In this study, we aimed to compare gastric emptying of radiopaque markers (ROM) and 13carbon-labelled gastric emptying breath tests for solids (GEBT). We also aimed to determine any association between gastric emptying and patient-reported symptoms, glycemic control and the patients' age, diabetes duration and occurrence of other late complications. Patients and methods: Forty-five patients (30 women, 15 men) with diabetes mellitus types 1 or 2 (40, 5) and symptoms of gastroparesis were examined with ROM and GEBT. All were interviewed, filled out symptom questionnaires and had HbA1c levels measured. Results: Forty percent of patients had delayed gastric emptying of ROM, while 55% had delayed gastric emptying of GEBT. Correlation between ROM and GEBT was not significant. Compared to GEBT, sensitivity for a positive ROM test was 0.52, while specificity was 0.74. In women, we found a higher specificity of 0.92, sensitivity 0.47. Difference in HbA1c between patients with positive and negative results was of borderline significance for both tests. GEBT (r=0.41, P=0.008) correlated with HbA1c. Patients with any late complications of diabetes had higher gastric retention of ROM (P=0.028), while patients with polyneuropathy (P=0.014) and diabetic wounds (P=0.004) had slower emptying with GEBT. None of the methods identified significant associations between gastric emptying and symptom scores, age or diabetes duration. Conclusions: As a measure of gastric emptying, the ROM test has benefits of being affordable and available. Compared to GEBT, the method has low diagnostic reliability. Before continued use, we recommend additional studies validating the test in diabetes patients.

13 C-Urea Breath Test Accuracy for Helicobacter pylori Infection in the Asian Population: A Meta-Analysis

Abstract: Background: Helicobacter pylori (H. pylori) infection is known to be associated with peptic ulcer and gastric cancer. Detection of H. pylori infection is a significant part of peptic ulcer and gastric cancer prevention and management. 13C-urea breath test (UBT) provides a good option for the pathogen detection due to its accuracy and safety. Objective: This review aims to evaluate the 13C-UBT diagnostic accuracy studies conducted among Asian population and validate its use for the Asian population. Methods: Original articles were systematically searched in PubMed, Scopus, and Google Scholar using the PICOS strategy by applying relevant keywords. Only studies published in English and conducted in Asia were included. Our search returned 276 articles. After assessment, 11 articles which answered our research question and met the criteria set for systematic review and meta-analysis were accepted. A total of 15 study protocols were extracted from the 11 accepted articles. Findings: Majority of the studies were conducted in Hong Kong (six), followed by Taiwan (five), Japan (two), and one each in Singapore and Israel. All studies had used histology as part of its gold standard of reference. All but one study was performed on adult populations. The summary estimate for sensitivity was 97% (95% CI: 96, 98%), and specificity was 96% (95% CI: 95, 97%), with significant heterogeneity between studies. Adjusting for the dose (50 mg) and breath sample collection time (20 minutes) had improved both accuracy estimates and significantly reduced heterogeneity. Conclusion: This review supports the test-and-treat strategy for H. pylori infection management. Prevalence and cost-effectiveness studies are mandatory for health authorities to adopt this strategy into national policy.

Congruency of Genetic Predisposition to Lactase Persistence and Lactose Breath Test.

Abstract: The physiological decline of lactase production in adulthood, in some individuals, is responsible for the so-called "Lactose Intolerance." This clinical syndrome presents with gastrointestinal and non-gastrointestinal symptoms following the consumption of dairy containing food. Lactose intolerance can be evaluated by means of the Lactose Breath Test (phenotype) and/or genetic evaluation of lactase-gene polymorphism (genotype). A comparison of the two tests was carried out in a large number of symptomatic adult subjects, which are selected and not representative of the general population. Congruency was as high as 88.6%. Among lactase non-persistent (genotype C/C), 14 subjects showed a negative Lactose Breath Test (LBT), possibly due to young age. Among lactase-persistent (genotype C/T), four subjects showed a positive LBT, which helps to diagnose secondary lactose intolerance. Symptoms, both gastrointestinal and extra-gastrointestinal, were reported by 90% of patients during the breath test. Clinical use of both tests in the same patients could be taken into consideration as a sharp diagnostic tool. We suggest considering the use of the genetic test after LBT administration, when secondary hypolactasia is suspected, for completion of diagnostic procedures.

Analysis of the Isotopic Composition of Exhaled Air by the Diode Laser Spectroscopy Method in the 2-μm Region for Diagnosis of Helicobacter pylori-Associated Diseases

Abstract: To diagnose digestive diseases associated with Helicobacter pylori infection, we applied laser spectroscopic analysis of the 13СО2/12СО2 isotope ratio in the exhaled air, which is based on the use of tunable diode lasers. To analyze the isotopic composition of the exhaled air, we developed a spectrophotometer based on a tunable diode laser. The 13СО2/12СО2 ratio was determined using the spectral range near 2.05 μm, in which the R-branch of the 20013–00001 band of 12СО2 overlaps with the P-branch of the 20012–0001 band of 13СО2. H. pylori infection in the gastrointestinal tract of a group of 309 subjects was diagnosed using the 13C-urea breath test (13C-UBT). The breath test results were compared with the results of morphological analysis of the gastric and duodenal mucosa specimens obtained during fiber gastroduodenoscopy. To compare the results of laser 13C-UBT and histology, we have for the first time proposed to use the total values of the results of the histological analysis of biopsy specimens taken in the body and distal part of the stomach and in the duodenum. The dependence of the results of laser 13C-UBT on the age, nosology, activity and severity of the inflammatory process, and the degree of atrophy and metaplasia, as well as the type of therapy was analyzed. It is shown that the distribution of the results of laser 13C-UBT in patients obtained before and after eradication therapy reflects the epidemiology of gastroduodenal diseases, the incidence of H. pylori infections, the patterns of gastrointestinal tract colonization by H. pylori, the parameters of inflammation, as well as the efficacy of therapy and the characteristics of the recovery of bacterial colonies after unsuccessful therapy.

Development of a 13 C Stable Isotope Assay for Dipeptidyl Peptidase-4 Enzyme Activity A New Breath Test for Dipeptidyl Peptidase Activity.

Abstract: Dipeptidyl peptidase-4 inhibitors (DPP4i) are a class of orally available, small molecule inhibitors for the management of Type-II diabetes. A rapid, real-time, functional breath test for DPP4 enzyme activity could help to define DPP4i efficacy in patients that are refractory to treatment. We aimed to develop a selective, non-invasive, stable-isotope 13C-breath test for DPP4. In vitro experiments were performed using high (Caco-2) and low (HeLa) DPP4 expressing cells. DPP gene expression was determined in cell lines by qRT-PCR. A DPP4 selective 13C-tripeptide was added to cells in the presence and absence of the DPP4 inhibitor Sitagliptin. Gas samples were collected from the cell headspace and 13CO2 content quantified by isotope ratio mass spectrometry (IRMS). DPP4 was highly expressed in Caco-2 cells compared to HeLa cells and using the 13C-tripeptide, we detected a high 13CO2 signal from Caco2 cells. Addition of Sitaglitpin to Caco2 cells significantly inhibited this 13CO2 signal. 13C-assay DPP4 activity correlated positively with the enzyme activity detected using a colorimetric substrate. We have developed a selective, non-invasive, 13C-assay for DPP4 that could have broad translational applications in diabetes and gastrointestinal disease.

Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane Analysis in Rat and Pig Models of Mesenteric Circulatory Distress.

Abstract: Objectives Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. Design Randomized, controlled in vivo animal study. Setting University research laboratory. Subjects Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). Interventions In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. Measurements and main results Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). Conclusions we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.

Potential for breath test diagnosis of urease positive pathogens in lung infections.

Abstract: Roles for urease in virulence are accepted for Helicobacter pylori and urinary tract pathogens. However, urease is widely expressed by bacterial and fungal lung pathogens causing emerging and opportunistic lung infections, organisms causing acute exacerbations of chronic bronchitis, mycobacterial lung diseases such as tuberculosis (TB), and ventilator associated pneumonia and health care associated pneumonia. Detection of urease provides a method for rapid in vivo detection of these lung pathogens by inhaled 13C- breath test, and this review discusses the range of lung pathogens that might be amenable to rapid diagnosis.

Effect of Hemodialysis on the Red Blood Cell Life Span in Patients with End-Stage Kidney Disease.

Abstract: The aim of this study was to use a CO breath test to investigate hemodialysis effects on red blood cell lifespan in patients with chronic kidney disease. A cohort of 17 non-smoking men with end-stage kidney disease undergoing hemodialysis via a polysulfone dialysis membrane (as opposed to a traditional cellulose acetate membrane) were subjected to a repeated Levitt's CO breath test to compare red blood cell lifespan before vs. after dialysis. None of the patients showed significant fluctuations in endogenous CO concentration during the dialysis procedure. The mean red blood cell lifespan was 66.0 ± 31.0 days before dialysis and 72.0 ± 26.0 days after dialysis, with no significant difference between the assessment time points (P > 0.05). In conclusion, dialysis using a polysulfone membrane did not appear to disrupt red blood cells or reduce their lifespan in patients with end-stage kidney disease.

Exhaled breath analysis in evaluation of psychological stress: A short literature review.

Abstract: Physiological stress is pervasive in today's society. Its detection is normally performed through several unobtrusive methods, driving both caregivers and patients to take measures to reduce the burden of this condition on human health. Among the methods for assessing stress, exhaled breath analysis represents a non-invasive, real-time alternative to classic laboratory tests. Therefore, a literature review was performed to assess the presence of altered parameters, related to psychological stress, in exhaled breath. Most studies in our review measured nitric oxide (NO), whose concentration was often correlated, either positively or negatively, with psychological stress, with reasonable scientific support. Other compounds (isoprene, terpene and so on) were rarely studied and with mixed evidence. Further investigations are needed to elucidate the involvement and the pathophysiological role of NO in stress, possibly including a greater number of individuals, as sample size actually represents the main limitation of the work published to date.

Breath analysis as promising indicator of hemodialysis efficiency

Abstract: The measurement of trimethylamine and isoprene in exhaled breath collected from dialysed patients indicates the changes in concentration of both compounds during dialysis. The aim of the presented study was to confirm diagnostic usefulness of TMA and isoprene detected in breath, as potential biomarkers of hemodialysis efficiency. The samples of exhaled breath were collected from 22 dialyzed patients (9 women, 13 men) before and after hemodialysis (HD). All analyses were carried out using a gas chromatograph equipped with a mass spectrometer. Thermal desorption was used as breath sample enrichment method. Chromatographic analysis of breath samples indicated statistically significant differences in trimethylamine (TMA) and 2-methyl-1,3-butadiene (isoprene) concentrations in patients’ breath collected before and after HD. TMA concentrations measured in breath samples, before dialysis, ranged from 0.024 to 0.461 nmol/L. After dialysis, the values of detected TMA were lower versus output values and ranged from 0.008 to 0.050 nmol/L. Isoprene concentrations before dialysis were present in the range from 0.236 to 9.718 nmol/L, after dialysis in the range from 0.478 to 26.182 nmol/L. Additionally, the dependences of TMA and isoprene concentrations, detected in breath with renal efficiency parameters detected in blood, were studied. The relationships between TMA and urea (r = 0.67; p < 0.00001) and creatinine (r = 0.61; p = 0.00002) were checked. In case of isoprene considerably higher concentrations were observed after dialysis, but no statistically significant correlation of isoprene with blood parameters was noticed. The observed decrease of TMA concentrations during dialysis could be useful as a measure of dialysis efficiency. The explanation of isoprene increase in breath during dialysis requires further investigation.

Prospective study for validation of a single protocol for the 13c-urea breath test using two different devices in the diagnosis of h. pylori infection.

Abstract: BACKGROUND: 13C-urea breath test (UBT) is the gold-standard, noninvasive method for H. pylori diagnosis. However, there is no uniform standardization of the test. This situation can be unpractical for laboratories running with two or more devices. OBJECTIVE: To perform a prospective comparison validation study of UBT employing one validated protocol for two different devices: BreathID Hp Lab System® (Exalenz Bioscience Ltd, Israel), here called device A and IRIS-Doc2® (Wagner Analysen-Technik, Germany, now Mayoly Spindler Group, France), here called device B, in the diagnosis of H. pylori infection. METHODS: A total of 518 consecutive patients (365 females, 153 males, mean age 53 years) referred for UBT were included. All patients received device A protocol as follow: after at least one hour fasting, patients filled two bags prior to the test, then ingested an aqueous solution containing 75 mg of 13C-urea with a 4.0 g citric acid powder and filled another two bags 15 min after ingesting the test solution. One pair of breath sample bags (before and after ingestion) was analyzed by the two different devices. A delta over baseline (DOB) ≥5‰ indicated H. pylori infection. Statistics: Wilcoxon test, kappa coefficient with 95% CI, Wilson’s method. RESULTS: Considering the device A protocol as the gold standard, its comparison with device B showed a sensitivity of 99.3% (95% CI: 96.3-99.9) and a specificity of 98.9% (95% CI: 97.3-99.6). Kappa coefficient was 0.976 (95% IC: 0.956-0.997). CONCLUSION: Correlation between the two devices was excellent and supports a uniform standardization of UBT.

Accuracy of the 13C-glucose breath test to identify insulin resistance in non-diabetic adults.

Abstract: To assess the validity of the 13C-glucose breath test (13C-GBT) to identify insulin resistance (IR) in non-diabetic individuals, using hyperinsulinemic–euglycemic clamps as gold standard. This validity was compared with that of other IR surrogates. Non-diabetic adults were studied in a cross-sectional design. In a first appointment, oral glucose tolerance tests were conducted simultaneously with 13C-GBTs. Oral 75 g glucose dissolved in 150 ml water, followed by 1.5 mg/Kg body weight U-13C-glucose dissolved in 50 ml water, was administered. Breath and blood samples were collected at baseline and at 30-min intervals. The percentages of glucose-oxidized dose at given periods were calculated. Clamps were conducted a week later. A clamp-derived M value ≤ 6.0 mg/kg*min was used as cut-off. ROC curves were constructed for 13C-GBT, fasting insulin, HOMA, and ISI-composite. Thirty-eight subjects completed the study protocol. The correlation coefficient between the 13C-GBT derived glucose-oxidized dose at 180 min and M values was 0.524 (p = 0.001). The optimal value to identify IR with the 13C-GBT was 4.23% (AUC 0.81; 95CI 0.66, 0.96; accuracy 0.82, 95CI 0.66, 0.92). The 13C-GBT sensitivity (0.88) was higher than HOMA and fasting insulin sensitivities (0.83 and 0.75 respectively), while their specificities were comparable (0.71, 0.71, and 0.79, respectively). The sensitivity of ISI-C was higher (0.92) than that of the 13C-GBT, but its specificity was poor (0.36). The accuracy of the 13C-GBT was superior to that of the other studied surrogates. The 13C-GBT is a valid and accurate method to detect IR in non-diabetic adults. Therefore, it is potentially useful in clinical and community settings.

Exhaled Volatile Organic Compounds Precedes Pulmonary Injury in a Swine Pulmonary Oxygen Toxicity Model

Abstract: Purpose: Inspiring high partial pressure of oxygen (FiO2 > 60%) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (PO2T). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO2 levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect PO2T prior to the onset of clinical symptoms. Methods: Male Yorkshire swine (20-30 kg) were placed into custom airtight runs and randomized to air (20.9% FiO2, n=12) or oxygen (>95% FiO2, n=10) for 72 hours. Breath samples, arterial blood gases, and vital signs were assessed every 12 hours. After 72 hours of exposure, animals were euthanized and the lungs processed for histology and wet-dry ratios. Results: Swine exposed to hyperoxia developed pulmonary injury consistent with PO2T. Histology of oxygen-exposed swine showed pulmonary lymphatic congestion, epithelial sloughing, and neutrophil transmigration. Pulmonary injury was also evidenced by increased interstitial edema and a decreased PaO2/FiO2 ratio in the oxygen group when compared to the air control group. Breath volatile organic compound (VOC) sample analysis identified six VOCs that were combined into an algorithm which generated a breath score predicting PO2T with a ROC/AUC curve of 0.72 defined as a decrement of PaO2/FiO2 ratio less than 350 mmHg. Conclusions: Exposing swine to 72 hours of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of PO2T. VOC analysis identified six VOCs in exhaled breath that preceded PO2T. Results show promise that a simple, non-invasive breath test could potentially predict the risk of pulmonary injury in humans exposed to high partial pressures of oxygen.