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Lactose malabsorption and lactose-induced symptoms are poorly correlated, as shown by breath tests and various symptom assessment methods. Validated assessment is the key to overcome the limitations of biased symptom measurements. We characterized lactose-induced symptoms with the population-specific, validated paediatric carbohydrate perception questionnaire (pCPQ) and their correlation with the history of symptoms (HoS).A total of 130 patients with functional gastrointestinal symptoms underwent a lactose hydrogen breath and tolerance test (LBTT) allowing for a diagnosis of malabsorption (M+) and lactose sensitivity (S+). HoS indicative of lactose-induced symptoms (abdominal pain, nausea, bloating, flatulence, diarrhoea) in the 4 weeks preceding the test was determined using a validated questionnaire. The pCPQ was used to score lactose-induced symptoms.The LBTT revealed 41 children (31.5%) with lactose malabsorption (M+), 56 (43.1%) with lactose sensitivity (S+) and 24 (18.5%) were M+/S+. Sensitivity correlated with HoS (P0.001), regardless of whether malabsorption was detectable. Malabsorption status did not correlate with HoS (NS). The odds of lactose sensitivity significantly increased when abdominal pain [odds ratio (OR) 3.5, confidence interval (CI) 1.6-7.8], nausea (OR 2.3, CI, 1.1-4.9) and flatulence (OR 3.1, CI 1.4-6.8) were reported in the 4 weeks preceding the LBTT. Symptoms after the lactose load were similar for M+/S+ and M-/S+, except for flatulence, which was more frequent in malabsorbers (P0.01).Our findings fit well with the emerging view of the important role of a validated symptom assessment after a lactose load. The determination of symptoms may be more relevant than malabsorption for the clinical outcomes of paediatric patients with lactose-related gastrointestinal symptoms.

Objective: Sobriety checkpoints have strong empirical and theoretical support as an intervention to reduce alcohol-involved motor vehicle crashes. The purpose of this study was to examine whether checkpoint size (the number of police officers) and checkpoint duration (the amount of time in operation) affect associations between individual checkpoints and subsequent alcohol-related crash incidence. Method: Queensland Police Service provided latitude–longitude coordinates and date and time data for all breath tests that occurred in Brisbane, Australia, from January 2012 to June 2018. We applied hierarchical cluster analysis to the latitude–longitude coordinates for breath tests, identifying checkpoints as clusters of ≥25 breath tests conducted by ≥3 breath testing devices over a duration of 3 to 8 hours. Generalized linear autoregressive moving average (GLARMA) models related counts of alcohol-involved motor vehicle crashes to the number of checkpoints conducted per week, as well as 1 week prior and 2 weeks prior. Results: A total of 3420 alcohol-related crashes occurred and 2069 checkpoints were conducted in Brisbane over the 6.5-year (339-week) study period. On average, checkpoints included a mean of 266.0 breath tests (SD = 216.3), 16.4 devices (SD = 13.7), and were 286.3 minutes in duration (SD = 104.2). Each 10 additional checkpoints were associated with a 12% decrease in crash incidence at a lag of 1 week (IRR = 0.88; 95%CI: 0.80, 0.97). We detected no differential associations according to checkpoint size or duration. Conclusions: Sobriety checkpoints are associated with fewer alcohol-related motor vehicle crashes for around 1 week. Checkpoint size and duration do not appear to affect this relationship.

The increased availability of noninvasive breath tests, each with limitations, has led to widespread testing for small intestinal bacterial overgrowth (SIBO) in patients with non-specific gastrointestinal complaints. The lactulose breath test (LBT) is based upon an incorrect premise and therefore incorrect interpretations which has resulted in the over-diagnosis of SIBO and the excessive use of antibiotics in clinical practice. Despite limitations, the glucose breath test (GBT) should be exclusively employed when considering SIBO in appropriately chosen patients. This review suggests guidelines for the optimal use and appropriate interpretation of the GBT for suspected SIBO. The LBT should be discarded from future use, and the literature based upon the LBT should be discounted accordingly.

Background Hydrogen-methane breath testing is widely used in both gastroenterology and complementary therapies practice, yet current guidelines do not detail preparatory oral hygiene, nor provide standards for basal gas levels. Aims To review and compare a range of instructions for oral hygiene prior to hydrogen-methane breath testing provided by facilities offering hydrogen-methane breath testing services; and to investigate laboratory interpretation of basal gas values and describe similarities, differences and management. Results Twenty-five laboratories from six countries provided information regarding breath testing preparation. In practice, there is a lack of uniformity in instructions for oral hygiene prior to breath testing, and where instructions exist, little or no attention is given to adherence. A wide variance in accepted norms for basal gases exists between centres, which may impact on whether testing commences or not. It remains unknown whether elevation at baseline negates test results or should indicate deferring the test. Conclusion There is no consensus on management of elevated basal gas levels. To improve the reliability of diagnostic results obtained from breath testing there is a pressing need for clarification of the impact of the role of oral hygiene on results, which should guide standardisation of instructions to include preparation of the oral cavity.

Purpose of review Pancreatic function tests are mainly used for the diagnosis of exocrine pancreatic insufficiency (EPI) in patients with pancreatic diseases or after pancreatic or gastric surgery. Breath tests evaluate not just pancreatic secretion but the digestion capacity of the pancreas. These tests are good candidates for the diagnosis of EPI as they are noninvasive, accurate and easy to apply to clinical practice. Recent findings The C-labelled mixed triglyceride (MTG) breath test has been optimized and validated against adequate reference methods for the diagnosis of EPI in patients with chronic pancreatitis and for the evaluation of the efficacy of pancreatic enzyme replacement therapy (PERT). In addition, reported C-MTG breath test results in patients with other pancreatic diseases and after pancreatic and gastric surgery support the accuracy and clinical applicability of this test. The evidence of pancreatic function breath tests with other C-labelled substrates is limited. Summary Increasing evidence supports the accuracy and clinical usefulness of the C-MTG breath test for the diagnosis of EPI and the evaluation of the efficacy of PERT in different clinical conditions. Commercial availability of this test is required for a wide clinical use. The use of optimized and validated breath test protocols is mandatory.

The article presents the data and review of the North American Consensus (2017) recommendations on the use of hydrogenmethane breathing test in diagnosing gastrointestinal disorders accompanied by excessive bacterial growth in the small intestine. On May 16, 2015, 17 leading scientists specializing in breathing tests took part in a consensus meeting in Washington (DC, USA). By a voting method, 28 consensus statements were identified and recommendations were given on the following issues regarding the use of the hydrogen-methane the procedure itself test in gastroenterological practice: 1) preparation for a breathing test; 2) indications for a breathing test; 3) the procedure itself; 4) interpretation of results; 5) gaps in the knowledge and unresolved issues.

PTH-6 Frigure 1Home breath tests[Figure omitted. See PDF]The average score given for ease of use for the home kit was 3.7/5. 10/14 (71%) of the patients accessed the video link and 4.3/5 said they would recommend this testing method to others.A follow up call was undertaken to ascertain the poor response rate from patients and common feedback included difficulty in understanding instructions, restrictive diet required prior to testing and time constraints.ConclusionsThe initial results from our pilot study show promise and suggest that home testing is a realistic, viable and cost-effective first line option for the management of SIBO in the post covid era.The poor response rate is a concern and steps to remedy this may include follow up telephone consultations, patient education and encouraging patients to access the video link to assist them in performing the test.

International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

Background: Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN).Objective: To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals.Design, setting, and participants: This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE).Outcome measurements and statistical analysis: Patient characteristics were statistically analyzed using independent sample t test and Pearson's chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER 3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method.Results and limitations: Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66-0.94) and 0.70 (95% CI 0.55-0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size.Conclusions: Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis.Patient summary: We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Sucrase deficiency has been implicated in chronic abdominal pain. Testing for sucrase deficiency generally involves invasive procedures or lengthy clinical visits, but now noninvasive kits that allow home testing are available to test for sucrase deficiency. In order to assess feasibility and utility of at-home testing, we reviewed our experience in 75 consecutive patients. All patients seen in the abdominal pain clinic had histories obtained in a standardized fashion and all had sucrase breath tests completed at home utilizing a commercially available kit. Testing was completed by 46 patients (61.3%). Tests were abnormal indicating sucrase deficiency in 34.8% of those completing testing. No symptoms were predictive of a positive test although there were trends of an association of an abnormal test with diarrhea and bloating. Our findings suggest that sucrase deficiency occurs frequently enough that more widespread testing and/or an empiric trial of sucrose and starch restriction should be considered.

Background Colorectal carcinoma (CRC) has a worldwide incidence of 1.4 million patients and a large share in cancer-related mortality. After curative treatment, the risk of recurrence is 30–65%. Early detection may result in curative treatment. However, current follow-up (FU) examinations have low sensitivity ranging from 49 to 85% and are associated with high costs. Therefore, the search for a new diagnostic tool is justified. Analysis of volatile organic compound in exhaled air through an electronic nose (eNose) is a promising new patient-friendly diagnostic tool. We studied whether the eNose under investigation, the Aeonose™, is able to detect local recurrence or metastases of CRC. Methods In this cross-sectional study we included 62 patients, all of whom underwent curative treatment for CRC in the past 5 years. Thirty-six of them had no metastases and 26 had extraluminal local recurrence or metastases of CRC, detected during FU. Breath testing was performed and machine learning was used to predict extraluminal recurrences or metastases, and based on the receiver operating characteristics (ROC)-curve both sensitivity and specificity were calculated. Results The eNose identified extra luminal local recurrences or metastases of CRC with a sensitivity and specificity of 0.88 (CI 0.69–0.97) and 0.75 (CI 0.57–0.87), respectively, with an overall accuracy of 0.81. Discussion This eNose may be a promising tool in detecting extraluminal local recurrences or metastases in the FU of curatively treated CRC. However, a well-designed prospective study is warranted to show its accuracy and predictive value before it can be used in clinical practice.

Aim: Delayed gastric emptying (GE) has been demonstrated in adults with type 1 diabetes mellitus (T1DM). Little is known about GE in children with T1DM. Most methods to measure GE are invasive, that is, scintigraphy, or are only indirectly related to GE, that is, electrogastrography. Carbon-13 breath testing is a non-invasive, very low-risk procedure that accurately correlates with GE time. This was a pilot study to determine the feasibility of using carbon-13 breath testing to measure GE in children with T1DM and healthy controls. Methods: Cases were recruited from children aged 7–15 years presenting to the paediatric diabetic clinic at Christchurch Hospital. Controls were peers of the cases. Children with known gastrointestinal disease were excluded. After an overnight fast, each child ate a standardised pancake labelled with carbon-13 sodium octanoate. Samples of breath were collected over a 4-h period. Samples were analysed by mass spectrometry. GE half time (GET1/2) and GE coefficients (GEC) were calculated by linear regression to obtain a measure of GE. Results: A total of 19 cases and 15 age- and gender-matched controls underwent testing. The mean GEC in the cases was 3.19 (±0.38) and 2.90 (±0.29) in controls (P = 0.03), with an effect size = 0.86. Mean GET1/2 in the cases was 99 (52.1) min and 103 (27.5) in controls (P = 0.8), with an effect size = 0.1. Conclusion: The study generated results suggesting that a larger study will be worthwhile to investigate the relationship between GE and T1DM Refereed/Peer-reviewed

Aim This study described outcomes following treatment for lactose intolerance, which is common in children. Methods The medical records of children aged 6-18 years who underwent lactose hydrogen breath testing at Dana-Dwek Children's Hospital, Tel Aviv, Israel, from August 2012 to August 2014 were analysed. We compared 154 children with gastrointestinal symptoms and positive lactose hydrogen breath tests to 49 children with negative test results. Results Of the 154 children in the study group, 89 (57.8%) were advised to follow a lactose-restricted diet, 32 (20.8%) were advised to avoid lactose completely, 18 (11.7%) were instructed to use substitute enzymes, and 15 (9.7%) did not receive specific recommendations. Only 11 patients (7.1%) received recommendations to add calcium-rich foods or calcium supplements to their diet. Lactose reintroduction was attempted in 119 of 154 patients (77.3%), and 65 of 154 (42.2%) experienced clinical relapses. At the final follow-up of 3.3 years, 62.3% of the study children were still observing a restricted diet. Older children and those who were symptomatic during lactose hydrogen breath testing were more likely to be on a prolonged restricted diet. Conclusion Our long-term follow-up of lactose-intolerant children showed that only a third were able to achieve a regular diet.

Human breath can contain thousands of volatile organic compounds (VOCs) and semi-volatile compounds that are related to metabolism and other biochemical processes. The presence of cancer cells can affect the identity and abundances of chemicals in breath when compared to those in healthy control subjects, which can be used to indicate the likelihood of a patient having cancer. Recently, the chemical analysis of exhaled breath from patients has been shown to be promising for diagnosing many different types of cancers, including lung, breast, colon, head, neck, and prostate, along with pre-cancerous conditions (dysplasia).Here, we reviewed the sampling, analytical and data analysis methods reported in the recent patent literature related to cancer breath testing (2014-2017). In addition, the different types of cancer biomarkers that were disclosed are discussed.The major advantages of breath testing compared to conventional X-ray and imaging based methods includes simplicity of use, non-invasiveness, and the potential to detect cancer at a relatively early stage. Such methods are also suitable to perform population screening because of their non-invasiveness. However, the establishment of standard sampling, detection and quantification methods for breath testing is required before the methods can be employed for clinical diagnosis.

Background This systematic review aims to assess the accuracy of hydrogen breath testing as a predictor of bowel preparation. Methods Studies were identified from MEDLINE, Embase, Web of Science, Cochrane Library and clinicaltrials.gov. Two investigators evaluated abstracts for inclusion criteria - report of correlation between hydrogen breath levels and bowel preparation quality, prospective design and non-emergent colonoscopy in adults. Included studies underwent duplicate data extraction using a standardized approach. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool assessed quality of the studies. Results One hundred fifty-nine publications were identified, and six unique studies met inclusion criteria. The number of patients analyzed ranged from 61 to 127. Three studies were performed in the USA, one in Japan and two in Italy. Three studies used a prebiotic in addition to a purgative, with the intention of enhancing the discriminating ability of hydrogen breath levels. Three studies assessed baseline hydrogen levels. In five of the six studies, hydrogen breath levels were predictive of inadequate bowel preparation. Suggested absolute hydrogen levels to distinguish adequate from inadequate bowel preparation ranged from 3 to 10 parts per million. Depending on the cutoff value, sensitivity ranged from 71% to 100% and specificity from 87% to 100%. There was significant heterogeneity among studies in breath testing protocol and breath analyzer used. Full-text studies had low risk of bias in most assessed domains. Conclusion Hydrogen breath levels predict bowel preparation adequacy but existing studies have significant limitations. Further studies should use standardized methods and consider the real-world practicality of self-administered home breath testing.

There are several procedures that are undertaken in order to help make a diagnosis or to assess a patient's response to treatment, or their disease progression. Hydrogen breath testing is one of these procedures. This test is used widely; it is a non-invasive way to assist with the diagnosis of a number of conditions. The test investigates the pathophysiology of functional gastrointestinal disorders. This article provides the reader with an overview of the hydrogen breath, with a focus on the procedure and a discussion of the role and function the healthcare assistant and the assistant practitioner (HCA and AP) play in relation to this procedure.

Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

There is evidence that children with malnutrition have an increased frequency of small intestinal bacterial overgrowth (SIBO) due to impaired gastric acidity, impaired intestinal motility, and dysbiosis. Children with malnutrition respond to antibiotic therapy but it is not clear if this effect is mediated by treatment of SIBO. We set out to determine the frequency of SIBO in children of varying nutritional status in a poor community in Lusaka, Zambia. Hydrogen breath testing, following a dose of 1g/kg oral glucose, was used to determine the presence of SIBO amongst the study participants. Forty nine children, 45 of whom had varying degrees of malnutrition, completed a full series of observations at 15, 30 and 60 minutes. Four children (8%) had a rise of 10ppm from baseline, consistent with SIBO. No correlation with nutritional status was observed. In this small study of Zambian children, SIBO was infrequent and unrelated to nutritional status.

Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm, which can be treated successfully only if correctly diagnosed and treated in early stages. The asbestos-exposed population serves as a high-risk group that could benefit from sensitive and specific blood- or tissue-based biomarkers. This review details the recent work with biomarker development in MPM and the contributions of the NCI Early Detection Research Network Biomarker Developmental Laboratory of NYU Langone Medical Center. The literature of the last 20 years was reviewed to comment on the most promising of the blood- and tissue-based biomarkers. Proteomic, genomic, and epigenomic platforms as well as novel studies such as “breath testing” are covered. Soluble mesothelin-related proteins (SMRP) have been characterized extensively and constitute an FDA-approved biomarker in plasma with diagnostic, monitoring, and prognostic value in MPM. Osteopontin is found to be a valuable prognostic biomarker for MPM, while its utility in diagnosis is slightly lower. Other biomarkers, such as calretinin, fibulin 3, and High-Mobility Group Box 1 (HMGB1), remain under study and need international validation trials with large cohorts of cases and controls to demonstrate any utility. The EDRN has played a key role in the development and testing of MPM biomarkers by enlisting collaborations all over the world. A comprehensive understanding of previously investigated biomarkers and their utility in screening and early diagnosis of MPM will provide guidance for further future research. See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”

BACKGROUND: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. AIMS: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. METHODS: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-hour gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. KEY RESULTS: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 hours and total GCSI scores did not differ significantly between those with and without SIBO. CONCLUSIONS: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.

OBJECTIVES: The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined. METHODS: Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was conducted before (day 1) and after (day 14) therapy (breath samples obtained every 15 minutes; up to 240 minutes). Patient response (decrease from baseline of ≥30% in abdominal pain and ≥50% decrease in frequency of mushy/watery stool), symptom improvement, and the relationship of clinical outcomes to LBT results were assessed. RESULTS: A total of 93 patients were included; 62 (66.7%) had positive baseline LBT results. Overall, 48.4% (45/93) of patients responded to rifaximin; of these, 59.7% (37/62) had a positive baseline LBT vs 25.8% (8/31) with a negative LBT (P = 0.002; odds ratio 4.3, 95% confidence interval, 1.5–12.7). Patients with a positive baseline LBT result experienced significantly greater improvement from baseline in 6 of 7 individual IBS symptoms. LBT results after rifaximin therapy did not correlate with clinical response in the 86 patients with evaluable breath tests (P = 0.21); however, patients whose LBT results normalized after rifaximin had the highest response rate of 76.5% (13/17). DISCUSSION: A positive baseline LBT result predicted a higher likelihood of response to rifaximin in IBS-D, suggesting a gut microbiome modulatory mechanism of action for rifaximin.

In clinical practice, caregivers of children with phenylketonuria (PKU) report that their children have breath malodour. This might be linked to the regular consumption of low phenylalanine (Phe)/Phe-free protein substitutes (PS), which are an essential component of a low-Phe diet. Oral malodour can negatively affect interpersonal communication, lead to bullying, low self-esteem and social isolation. In this longitudinal cross-over study, exhaled volatile organic compounds (VOCs) were measured using gas chromatography - ion mobility spectrometry (GC-IMS). 40 children (20 PKU, 20 controls) were recruited. Subjects with PKU took either L-Amino Acid (L-AA) or Casein Glycomacropeptide (CGMP-AA) exclusively for 1 week, in a randomised order. On the 7th day, 7 exhaled breath samples were collected over a 10-hr period. Subjects then transferred to the other PS for a week and on day 7, provided 7 further breath samples. All subjects had a standardised menu using low-Phe food alternatives and all food intake was measured and recorded. In the PKU group, the aim was to collect samples 30-min after consuming PS. In 3 subjects, breath was collected 5-min post-PS consumption. Fasted L-AA and CGMP-AA breath samples contained a similar number of VOC peaks (10-12) as controls. Longitudinal breath testing results demonstrate that there was no significant difference in the number of exhaled VOCs, comparing L-AA or CGMP-AA with controls, or between PS (12-18 VOC peaks). Breath analysed immediately after consumption of PS (n=3) showed an immediate increase in the number of VOC peaks (25-30), but these were no longer detectable at 30-min post-consumption. This suggests PS have a transient effect on exhaled breath. Measurements taken 30-min after consuming L-AA or CGMP-AA were not significantly different to controls. This indicates that timing food and drinks with PS consumption may be a potential solution for carers to reduce or eliminate unpleasant PS-related breath odours. [Abstract copyright: © 2019 IOP Publishing Ltd.]

Background Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. Methods To estimate the diagnostic accuracy of breath test with electronic-nose and other devices against culture or other tests for TB, we screened multiple databases until January 6, 2019. Findings We included fourteen studies, with 1715 subjects in the analysis. The pooled sensitivity and specificity of electronic-nose were 0.93 (95% CI 0.82–0.97) and 0.93 (95% CI 0.82–0.97), respectively, and no heterogeneity was found. The sensitivity and specificity of other breath test devices ranged from 0.62 to 1.00, and 0.11 to 0.84, respectively. Interpretation The low to moderate evidence of these studies shows that breath tests can diagnose TB accurately, however, to give a real-time test result, additional development is needed. Research should also focus on sputum smear negative TB, children, and the positioning of breath testing in the diagnostic work flow. Funding The authors received no specific funding for this work.

Background A hydrogen breath test is an inexpensive, non-invasive and safe diagnostic test used to investigate intestinal disorders, including suspected Small Intestinal Bacterial Overgrowth (SIBO). The recent publication of the North American Consensus statement1 suggests a rise ≥20 ppm of hydrogen within 90 min as an ideal threshold for a positive test to suggest the presence of SIBO following ingestion of glucose or lactulose. As lactulose is a non-digestible disaccharide, it is possible that such a rise during a lactulose test is due to fermentation in the colon, rather than an indicator of SIBO. A small retrospective audit was undertaken to investigate how many patients with a positive lactulose test for SIBO had a subsequent positive glucose test. Methods Adult patients who had previously attended for a lactulose hydrogen breath test which established the presence of hydrogen-producing bacteria and met the diagnostic criteria for SIBO were included in this audit. All patients attended for a glucose hydrogen breath test within 6 weeks of their lactulose breath test, and had not received antibiotic therapy during this time period. After a baseline reading, patients provided a breath-hydrogen sample every 15 min for 60 min post ingestion of a glucose solution. Further breath hydrogen samples were then taken every 30 min for 180 min. Results were analysed to determine the number of patients who met the diagnostic criteria for SIBO (≥20 ppm rise in hydrogen above baseline within 180 min). Results 18 patients (11F, 7M) were included in this small audit. 2 patients (F) were found to be positive for SIBO, whereas 16 patients (9F, 7M) were concluded to be negative, as they did not demonstrate a significant rise in expired hydrogen (≥20 ppm above baseline) within 180 min. 11.1% of patients included in this audit had SIBO confirmed with a glucose hydrogen breath test, despite all having a positive lactulose test using the criteria suggested in the North American Consensus paper. Conclusion Based on the lactulose results alone, the majority of patients in this audit (88.9%) would have been reported as having a SIBO, despite a negative glucose test. Using lactulose alone as a substrate to diagnose SIBO may therefore provide a false positive result, potentially leading to misdiagnosis and inappropriate use of antibiotics. Reference Rezaie A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. The American journal of gastroenterology. 2017;112(5):77–4.

Background Despite implementation of enhanced recovery after surgery (ERAS) and laparoscopic techniques, postoperative ileus (POI) remains frequent after colorectal surgery, impacting the patient, their recovery and health-care resources. Presently there are no tests that reliably predict or enable early POI diagnosis. Volatile organic compounds (VC) are products of human and microbiota cellular metabolism and we hypothesised that a detectable alteration occurs in POI. Method This was a prospective observational study of patients undergoing laparoscopic colorectal resection within an established ERAS programme. Standardized end-expiratory breath sampling was performed on the morning of surgery and on the first three postoperative mornings. The concentrations of VCs commonly found in intestinal gas were analysed using selected ion flow tube mass spectrometry and GastroCH4 ECK®. Feasibility data, bowel preparation, postoperative oral intake, POI and 30-day morbidity were recorded. Results Of the 75 potentially eligible patients, 58 (77%) agreed to participate. Per-protocol breath sampling was successfully completed in 94%. There were no analytical failures. Baseline and postoperative concentrations of VCs were broadly comparable and were not altered by bowel preparation or postoperative oral intake. POI developed in 14 (29%) patients. Preoperative ammonia concentration was higher in patients who developed POI [830 parts per billion (ppb) vs 510 ppb, P = 0.027]. There was an increase in the concentration of acetic acid detected on day 2 in patients who developed POI (99 ppb vs 171 ppb, P = 0.021). Conclusion Repeated VC breath sampling and analysis is feasible in the perioperative setting. An elevated ammonia concentration on the morning of surgery may be a potential predictor of POI.

Helicobacter pylori infection is the leading cause of peptic ulcer disease. The purpose of this study was, first, to assess the difference in the distribution of negative versus positive results between the older 14C-urea breath test and the newer 13C-urea breath test and, second, to determine whether use of an indeterminate-results category is still meaningful and what type of results should trigger repeated testing. Methods: A retrospective survey was performed of all consecutive patients referred to our service for urea breath testing. We analyzed 562 patients who had undergone testing with 14C-urea and 454 patients who had undergone testing with 13C-urea. Results: In comparison with the wide distribution of negative 14C results, negative 13C results were distributed farther from the cutoff and were grouped more tightly around the mean negative value. Distribution analysis of the negative results for 13C testing, compared with those for 14C testing, revealed a statistically significant difference between the two. Within the 13C group, only 1 patient could have been classified as having indeterminate results using the same indeterminate zone as was used for the 14C group. This is significantly less frequent than what was found for the 14C group. Discussion: Borderline-negative results do occur with 13C-urea breath testing, although less frequently than with 14C-urea breath testing, and we will be carefully monitoring differences falling between 3.0 and 3.5 %Δ. 13C-urea breath testing is safe and simple for the patient and, in most cases, provides clearer positive or negative results for the clinician.

Retrospective analysis of the incidence of Radio Frequency Interference (RFI) exception messages obtained during testing of suspected impaired drivers on the Intoxilyzer® 5000C over a 13-year period (1997 to 2009) was examined in order to address concerns on the hypothetical impact of RFI on breath alcohol testing. RFI messages were rare, occurring in less than 0.48% (n = 128) of the 26,939 drivers tested. Multiple RFI messages were even more infrequent, occurring in only 10.2% of RFI-positive cases (n = 13). There was no significant effect of the incidence of RFI messages attributable to a particular testing location (p = 0.98), a specific instrument (p = 0.98), or year of testing (p = 0.99). In addition, the data show no evidence that hypothetical “undetected” RFI events, in addition to those already detected by the instrument, affected either the calibration check results or the subject breath tests in this study. Instruments are designed with an RFI detection system and shielding to protect th...

In the current pilot study we aimed to determine whether breath analysis could be used to help recognise intra-abdominal infection, using acute appendicitis as an exemplar condition. Our study included 53 patients (aged 18–88 years) divided into three groups: appendix group, 26 (13 male) patients suffering from acute appendicitis; control group 20 (seven male) patients undergoing elective abdominal surgery; normal group, seven patients who were clinically diagnosed with appendicitis, but whose appendix was normal on histological examination. Samples of breath were analysed using ion molecule reaction mass spectroscopy measuring the concentration of volatile compounds (VCs) with molecular masses 27–123. Intraperitoneal gas samples were collected from a subset of 23 patients (nine diagnosed with acute appendicitis). Statistically significant differences in the concentration of VCs in breath were found between the three groups. Acetone, isopropanol, propanol, butyric acid, and further unassigned VCs with molecular mass/charge ratio (m/z) 56, 61 and 87 were all identified with significant endogenous contributions. Principle component analysis was able to separate the control and appendicitis groups for seven variables: m/z = 56, 58, 59, 60, 61, 87 and 88. Comparing breath and intraperitoneal samples showed significant relationships for acetone and the VC with m/z = 61. Our data suggest that it may be possible to help diagnose acute appendicitis by breath analysis; however, factors such as length of starvation remain to be properly accounted for and the management or mitigation of background levels needs to be properly addressed, and larger studies relating breath VCs to the causative organisms may help to highlight the relative importance of individual VCs.

Lung cancer (LC) is a leading cause of cancer-related morbidity and mortality globally, and exhaled breath testing has been considered as a fast, convenient and non-invasive way to diagnose LC in its early stages. Volatile organic compounds (VOCs), as markers of LC in exhaled breath, have been widely investigated for cancer diagnosis. However, few studies have reported on the interference of benign pulmonary diseases (BPD) in the selection of VOC markers for LC. During this study, 207 samples were analyzed using thermal desorption instrumentation/gas chromatography/mass spectrometry (TD-GCMS) to detect C6-C30 VOCs, and all samples were divided into four groups: LC group, BPD group, lung disease (LD) group (including LC group and BPD group) and healthy group. To make up for the deficiency of detecting low carbon hydrocarbons (

Introduction Gastrointestinal (GI) cancers are a major cause of morbidity and mortality, yet symptoms are common and non-specific. A non-invasive breath test may be a useful tool for triaging for endoscopy/CT those without red-flag symptoms, or possibly for screening. Prior studies have shown promising results of a breath test for oesophagogastric (80% sensitivity/81% specificity) and colorectal (96% sensitivity/76% specificity) cancers. The Breath MAGIC (Models for Assessment of GI Cancer) study investigates feasibility and acceptability of breath testing in Primary Care. We also developed a quality control (QC) system for breath sampling. Methods This is an prospective cohort study of patients attending their GP for current/recent GI symptoms, from November 2016-May 2017, recruitment target 500. Exhaled breath (250mls) was collected by GP practice/NIHR research nurses using the ReCIVA breath sampling device, onto thermal desorption tubes. Breath volatile organic compounds (VOCs) were analysed using Gas Chromatography (GC) and Proton Transfer Reaction (PTR) Mass Spectrometry, at St Mary’s Hospital VOC laboratory. This platform allows analysis of 100 samples per day of continuous, unattended operation. Patients were recruited from 16 London GP practices on the day or were prebooked via phone/text. Feasibility and acceptability were measured using field notes, a telephone conference then focus group of research nurses (thematicially analysed), and GP questionnaires. To develop a QC system, 76 ‘good quality’ samples taken by one experienced operator were used as a standard. Results Plan-Do-Study-Act cycles from field notes identified barriers and drove regular improvements e.g. phone/text recruitment, a GP poster, grouping of nearby practices, and training healthcare assistants to breath-test. In total 636 patients were enrolled, suggesting breath testing is feasible in Primary Care. Sampling was feasible, with some equipment-related but few patient-related limiting factors reported. Analysis was also feasible, with 34% and 55% of samples analysed within 50 ppb (H3O+ionisation, PTR) and isoprene >2.5 ppb (NO +ionisation, PTR). This was validated on 284 separate patients’ samples. A process was also developed to interrogate ReCIVA software sampling data. Conclusions Breath testing is feasible in Primary Care, from a human factors and process perspective. This finding, and the development of a QC process, opens up the possibility of large-scale breath testing, pending results of diagnostic accuracy studies. A revised recruitment target of 1000 with new patient acceptability questionniares will likely provide further evidence for this.

Introduction The North American Consensus (NAC) document on breath testing published in 2017 was a first attempt to standardise the diagnostic test for small intestinal bacterial overgrowth (SIBO), including two key recommendations in terms of substrate dosing. The recommended use of 10 g lactulose and 75 g glucose differed from many practices in the UK which used 16 g of lactulose and 50 g of glucose previously, therefore we adopted these new dosing parameters and retrospectively compared these data to those acquired in the previous 3 months. Methods Data from 536 patients were analysed and distinguished into subgroups dependent on substrate-10 g lactulose (n=200), 16 g lactulose (n=200), 75 g glucose (n=82) and 50 g glucose (n=54). Unpaired t-tests were used to determine statistical significance of the results. Results Patients in the higher dose groups for glucose and lactulose had significantly more SIBO positive results (as determined by a rise >10 ppm above baseline in hydrogen in 60 min post ingestion) than those in the lower dose groups (lactulose p=0.0279, glucose p=0.0427). There was no significant difference in methane between groups (p>0.05 for both). The change in glucose and lactulose dose did not have any significant effect on number of patients recording symptoms throughout the test (bloating, nausea or abdominal pain) (p>0.05 for both), however recorded severity of bloating was significantly higher in patients administered 16 g lactulose than those administered 10 g (p=0.0415). With the 10 g lactulose dose, patients with a positive SIBO test experienced significantly more bloating and nausea than negative patients (bloating p=0.0467, nausea p=0.0327), but this difference was not observed in the 16 g lactulose group (p>0.05 for both). Symptoms were equivalent in the glucose groups. Conclusions Glucose (75 g) yields a higher proportion of positive results for SIBO than 50 g without an increase in symptoms. As glucose is absorbed in the proximal small bowel these are likely to be true positives. 16 g of lactulose yielded significantly more positive results than 10 g, but as higher lactulose doses have been shown to reduce intestinal transit time it is possible that these may represent false positive test for SIBO. This is supported by the fact that 16 g of lactulose induced equivalent symptoms in SIBO positive and negative patients whereas 10 g only increased symptoms in SIBO positive patients. These findings broadly support the parameters outlined in the NAC document for SIBO testing.

Introduction Hydrogen breath testing (BT) is a useful non-invasive test for diagnosing small intestinal bacterial overgrowth (SIBO) and carbohydrate maldigestion. In a proportion of patients methane is produced at the expense of hydrogen leading to false negative results. This retrospective study evaluated the diagnostic yield of methane testing in addition to hydrogen. Methods Electronic records were interrogated for the results of all glucose and lactose BT performed for SIBO and lactose intolerance respectively between 22/05/2015 and 03/01/2018 using the GastroCH4ECK® machine, Bedfont® Scientific Ltd. Results During the study interval 569 patients (age range 16–86 y, 66% female) were referred for BT with glucose (48.5%) or lactose challenge (51.5%). Hydrogen and methane production was positive in 10.1% (71.4% female) and 4.7% (61.5% female) of patients undergoing glucose BT for SIBO. Two patients were hydrogen/methane co-producers. Hence 28.2% of patients with SIBO solely produced methane and would have been missed with only hydrogen assessment. Hydrogen and methane production was positive in 25.6% (80.0% female) and 5.1% (68% female) of patients undergoing lactose BT for lactose malabsorption respectively. Two patients were hydrogen/methane co-producers. 14.8% of patients with positive lactose BT only produced methane and would have been missed with hydrogen mono-testing. Overall 18.9% of all patients with a positive BT (n=24, 75% female) were sole methane-producers that would have been misdiagnosed if hydrogen mono-testing was conducted. Conclusions In this study we have demonstrated that combined hydrogen/methane BT helps optimise diagnosis in patients with suspected SIBO or lactose intolerance. An extra 28.2% of positive breath tests for patients with SIBO and 14.8% for lactose malabsorption were identified with the addition of methane to hydrogen testing. Interestingly the proportion of patients producing methane was higher in SIBO than lactose malabsorption. Compared with the overall study population, a greater proportion of males tested positive for methane on glucose challenge. In comparison a greater proportion of females were methane positive on lactose BT. Currently only the minority of centres offer methane testing and our results suggest that a significant number of patients with possible SIBO or lactose malabsorption may be missed. Methane BT should be considered particularly for male patients with suspected SIBO.

Introduction The acquisition parameters and interpretation of breath testing data for the assessment of carbohydrate malabsorption (CM) varies widely between centres. The North American Consensus (NAC) document on breath testing published in 2017 was a first attempt to standardise this diagnostic test. Two key recommendations were to extend the period of post ingestion breath sampling from 120 to 180 min and that SIBO should be excluded prior to CM testing. We retrospectively assessed our database of CM studies from the previous 12 months to examine the impact of these recommendations on results. Methods Patient data was retrospectively attributed to 120 min and 180 min groups for both lactose and fructose breath tests. All patients provided a baseline sample prior to ingestion of 25 g of either substrate following a 24 hour restrictive diet and 12 hour fast. In total 200 breath tests were analysed (120-lactose and 80-fructose). A rise >20 ppm above baseline was considered positive for CM. The results were compared statistically using Pearson’s chi-squared test. Results A positive result for CM at 120 min was seen in 27 of 120 (22.5%) subjects for lactose and 33 of 80 (36.3%) subjects for fructose. When extended to 180 min the number of positive CM tests increased to 30% and 41.3% for lactose and fructose, respectively. Within these sub-groups the significant rise in gas levels occurred at ≤60 min after ingestion in 34.3% for lactose and 69.8% for fructose. There was a significant association between patients who had a positive SIBO test (as determined by a separate lactulose test) and a positive breath test for lactose at ≤60 min [χ2≥5.3, p0.02]. Findings for fructose were not significant [p>0.05]. Conclusions Around 20% of the positive results for CM occurred after 120 min supporting the NAC position to extend the post ingestion period to 180 min to avoid false negative studies. SIBO may influence results and a lactulose breath test should be performed prior to CM testing to avoid false positive tests and to help interpret CM studies with greater accuracy. Like the first iteration of the Chicago Classification for oesophageal motility testing – the NAC on breath testing represents a positive first step in standardising these diagnostic tests.

Exhaled breath is a robust matrix of biomarkers divided between three fractions – gaseous breath, volatile breath, and breath condensate. Breath is collected non-invasively through bags (for gaseous breath), cold condensation chambers (breath condensate), and adsorbent traps (volatile breath). Due to the incredibly dilute nature of breath matrices, breath biomarker analysis requires precise analytical techniques, highly sensitive technology and often challenges the limit of detection of even the most advanced assays. Interest and advances in breath collection, analysis, and use have increased in recent years largely due to advances in analytical technology. Approved and validated breath tests are available as tools for researchers and clinicians. Novel development is ongoing. This article reviews the current applications for exhaled breath biomarkers.

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC-MS) for identification and quantification of volatile organic compounds (VOCs). The T-test was used to identify significant VOCs (p values

Volatile organic compounds present in the exhaled breath have shown promise as biomarkers of lung cancer. Advances in colorimetric sensor array technology, breath collection methods, and clinical phenotyping may lead to the development of a more accurate breath biomarker.Perform a discovery-level assessment of the accuracy of a colorimetric sensor array-based volatile breath biomarker.Subjects with biopsy-confirmed untreated lung cancer, and others at risk for developing lung cancer, performed tidal breathing into a breath collection instrument designed to expose a colorimetric sensor array to the alveolar portion of the breath. Random forest models were built from the sensor output of 70% of the study subjects and were tested against the remaining 30%. Models were developed to separate cancer and subgroups from control, and to characterize the cancer. Additional models were developed after matching the clinical phenotypes of cancer and control subjects.Ninety-seven subjects with lung cancer and 182 control subjects participated. The accuracies, reported as C-statistics, for models of cancer and subgroups versus control ranged from 0.794 to 0.861. The accuracy was improved by developing models for cancer and control groups selected through propensity matching for clinical variables. A model built using only subjects from the largest available clinical subgroup (49 subjects) had a C-statistic of 0.982. Models developed and tested to characterize cancer histology, and to compare early- with late-stage cancer, had C-statistics of 0.881-0.960.The colorimetric sensor array signature of exhaled breath volatile organic compounds was capable of distinguishing patients with lung cancer from clinically relevant control subjects in a discovery level trial. The incorporation of clinical phenotypes into the further development of this biomarker may optimize its accuracy.

Carbon-labeled urea breath tests, which have high sensitivity and specificity, are the preferred method used in epidemiological studies, screening dyspeptic patients and assessing eradication or recurrence of Helicobacter pylori infection. The principle of the (13)C-urea breath test relies upon the ability of the H. pylori urease to hydrolyze the orally administered (13)C-urea. The BreathID (Exalenz Bioscience Inc., Union, NJ, USA) provides a competitive solution for breath testing, including unique features such as automatic continuous breath collection and analysis. This is an unattended convenient test, with no human error as the correct part of the breath is collected and patients' assistance is not required. The test results are available in real time at the point of care and enable shortened breath testing procedures. Additionally, several studies showing expanded utility of the BreathID in pediatrics, after therapy and during proton pump inhibitors intake, further support the safety and performance of the BreathID in the diagnosis of H. pylori.

Gastric emptying studies generally measures overall gastric emptying. They are primarily used to help diagnose patients with gastroparesis. The can also be useful for detecting rapid gastric emptying which might suggest dumping syndrome. There are three types of gastric emptying studies approved for clinical use: gastric emptying scintigraphy, breath testing using stable nonradioactive C-13 isotope, and wireless motility capsule. In addition, ultrasonography and magnetic resonance imaging (MRI) can be used to assess gastric emptying in clinical research studies. This chapter will discuss each of these tests mentioning aspects on how to perform the tests, how to interpret the tests, and use in patient management.

Many uremic solutes retained in chronic kidney disease are volatile, and can be detected by breath testing. We compared the exhaled breath of subjects with end stage renal disease (ESRD) to healthy volunteers to identify volatile compounds that can serve as a potential breathprint for renal failure. We analyzed the exhaled breath of 86 ESRD subjects and 25 healthy volunteers using selected-ion flow-tube mass spectrometry (SIFT-MS). Using a random forests classification model, we identified three known volatiles (2-propanol, ammonia, acetaldehyde) and two unknown volatiles ( NO+76) that were highly significant for discriminating individuals with renal failure from individuals without renal failure (C statistic > 0.99). This study provides preliminary support for the use of exhaled breath as a potential noninvasive screening tool in renal failure.