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Clinical Microbiology Reviews Sep 2022Despite the recent decrease in overall prevalence of Helicobacter pylori infection, morbidity and mortality rates associated with gastric cancer remain high. The... (Review)
Review
Despite the recent decrease in overall prevalence of Helicobacter pylori infection, morbidity and mortality rates associated with gastric cancer remain high. The antimicrobial resistance developments and treatment failure are fueling the global burden of H. pylori-associated gastric complications. Accurate diagnosis remains the opening move for treatment and eradication of infections caused by microorganisms. Although several reports have been published on diagnostic approaches for H. pylori infection, most lack the data regarding diagnosis from a clinical perspective. Therefore, we provide an intensive, comprehensive, and updated description of the currently available diagnostic methods that can help clinicians, infection diagnosis professionals, and H. pylori researchers working on infection epidemiology to broaden their understanding and to select appropriate diagnostic methods. We also emphasize appropriate diagnostic approaches based on clinical settings (either clinical diagnosis or mass screening), patient factors (either age or other predisposing factors), and clinical factors (either upper gastrointestinal bleeding or partial gastrectomy) and appropriate methods to be considered for evaluating eradication efficacy. Furthermore, to cope with the increasing trend of antimicrobial resistance, a better understanding of its emergence and current diagnostic approaches for resistance detection remain inevitable.
Topics: Anti-Bacterial Agents; Breath Tests; Clinical Laboratory Techniques; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Sensitivity and Specificity
PubMed: 35404105
DOI: 10.1128/cmr.00258-21 -
United European Gastroenterology Journal Feb 2022Measurement of breath hydrogen (H ) and methane (CH ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of... (Review)
Review
European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric...
INTRODUCTION
Measurement of breath hydrogen (H ) and methane (CH ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline.
METHODS
This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H -CH -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria.
RESULTS
The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H -CH -breath tests in these indications and recommends approaches to mitigate these issues.
CONCLUSION
This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.
Topics: Adult; Breath Tests; Carbohydrate Metabolism; Child; Consensus; Dietary Carbohydrates; Dysbiosis; Endoscopy, Digestive System; Europe; Gastroenterology; Gastrointestinal Microbiome; Gastrointestinal Transit; Humans; Hydrogen; Intestine, Small; Malabsorption Syndromes; Methane; Nutritional Sciences; Societies, Medical; Symptom Assessment
PubMed: 34431620
DOI: 10.1002/ueg2.12133 -
Clinical and Translational... Apr 2023There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and... (Review)
Review
There is increasing appreciation that small intestinal bacterial overgrowth (SIBO) drives many common gastrointestinal symptoms, including diarrhea, bloating, and abdominal pain. Breath testing via measurement of exhaled hydrogen and methane gases following ingestion of a readily metabolized carbohydrate has become an important noninvasive testing paradigm to help diagnose SIBO. However, because of a number of physiological and technical considerations, how and when to use breath testing in the diagnosis of SIBO remains a nuanced clinical decision. This narrative review provides a comprehensive overview of breath testing paradigms including the indications for testing, how to administer the test, and how patient factors influence breath testing results. We also explore the performance characteristics of breath testing (sensitivity, specificity, positive and negative predictive values, likelihood ratios, and diagnostic odds ratio). Additionally, we describe complementary and alternative tests for diagnosing SIBO. We discuss applications of breath testing for research. Current estimates of SIBO prevalence among commonly encountered high-risk populations are reviewed to provide pretest probability estimates under a variety of clinical situations. Finally, we discuss how to integrate breath test performance characteristics into clinical care decisions using clinical predictors and the Fagan nomogram.
Topics: Humans; Intestine, Small; Methane; Diarrhea; Hydrogen; Breath Tests
PubMed: 36744854
DOI: 10.14309/ctg.0000000000000567 -
EBioMedicine Aug 2019Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. (Meta-Analysis)
Meta-Analysis
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.
Topics: Biosensing Techniques; Breath Tests; Electronic Nose; Female; Humans; Male; Mycobacterium tuberculosis; ROC Curve; Reproducibility of Results; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Pulmonary; Volatile Organic Compounds
PubMed: 31401197
DOI: 10.1016/j.ebiom.2019.07.056 -
Nutrients Dec 2022The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the... (Review)
Review
The microbiota, as a complex of microorganisms in a particular ecosystem, is part of the wider term-microbiome, which is defined as the set of all genetic content in the microbial community. Imbalanced gut microbiota has a great impact on the homeostasis of the organism. Dysbiosis, as a disturbance in bacterial balance, might trigger or exacerbate the course of different pathologies. Small intestinal bacterial overgrowth (SIBO) is a disorder characterized by differences in quantity, quality, and location of the small intestine microbiota. SIBO underlies symptoms associated with functional gastrointestinal disorders (FGD) as well as may alter the presentation of chronic diseases such as heart failure, diabetes, etc. In recent years there has been growing interest in the influence of SIBO and its impact on the whole human body as well as individual systems. Therefore, we aimed to investigate the co-existence of SIBO with different medical conditions. The PubMed database was searched up to July 2022 and we found 580 original studies; inclusion and exclusion criteria let us identify 112 eligible articles, which are quoted in this paper. The present SIBO diagnostic methods could be divided into two groups-invasive, the gold standard-small intestine aspirate culture, and non-invasive, breath tests (BT). Over the years scientists have explored SIBO and its associations with other diseases. Its role has been confirmed not only in gastroenterology but also in cardiology, endocrinology, neurology, rheumatology, and nephrology. Antibiotic therapy could reduce SIBO occurrence resulting not only in the relief of FGD symptoms but also manifestations of comorbid diseases. Although more research is needed, the link between SIBO and other diseases is an important pathway for scientists to follow.
Topics: Humans; Intestine, Small; Anti-Bacterial Agents; Blind Loop Syndrome; Irritable Bowel Syndrome; Microbiota; Breath Tests
PubMed: 36615748
DOI: 10.3390/nu15010090 -
The Cochrane Database of Systematic... Mar 2018Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori.
OBJECTIVES
To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started.
SEARCH METHODS
We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively.
SELECTION CRITERIA
We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as C or C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities.
MAIN RESULTS
We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-C; 21 studies (1810 participants) evaluated urea breath test-C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-C, urea breath test-C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-C, urea breath test-C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-C, urea breath test-C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons.
AUTHORS' CONCLUSIONS
In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
Topics: Adult; Antigens, Bacterial; Biomarkers; Breath Tests; Child; Feces; Helicobacter Infections; Helicobacter pylori; Humans; Prevalence; Urea
PubMed: 29543326
DOI: 10.1002/14651858.CD012080.pub2 -
Gut and Liver Mar 2017The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this... (Review)
Review
The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.
Topics: Adult; Anti-Bacterial Agents; Biopsy; Blind Loop Syndrome; Breath Tests; Female; Humans; Intestine, Small; Irritable Bowel Syndrome; Male; Middle Aged; Probiotics; Risk Factors
PubMed: 28274108
DOI: 10.5009/gnl16126 -
BMJ Open Diabetes Research & Care May 2021The review aimed to investigate the accuracy of breath tests in the diagnosis of diabetes mellitus, identify exhaled volatile organic compounds with the most evidence as... (Meta-Analysis)
Meta-Analysis Review
The review aimed to investigate the accuracy of breath tests in the diagnosis of diabetes mellitus, identify exhaled volatile organic compounds with the most evidence as potential biomarkers, and summarize prospects and challenges in diabetic breath tests. Databases including Medline, PubMed, EMBASE, Cochrane Library and Science Citation Index Expanded were searched. Human studies describing diabetic breath analysis with more than 10 subjects as controls and patients were included. Population demographics, breath test conditions, biomarkers, analytical techniques and diagnostic accuracy were extracted. Quality assessment was performed with the Standards for Reporting Diagnostic Accuracy and a modified QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Forty-four research with 2699 patients with diabetes were included for qualitative data analysis and 14 eligible studies were used for meta-analysis. Pooled analysis of type 2 diabetes breath test exhibited sensitivity of 91.8% (95% CI 83.6% to 96.1%), specificity of 92.1% (95% CI 88.4% to 94.7%) and area under the curve (AUC) of 0.96 (95% CI 0.94 to 0.97). Isotopic carbon dioxide (CO) showed the best diagnostic accuracy with pooled sensitivity of 0.949 (95% CI 0.870 to 0.981), specificity of 0.946 (95% CI 0.891 to 0.975) and AUC of 0.98 (95% CI 0.97 to 0.99). As the most widely reported biomarker, acetone showed moderate diagnostic accuracy with pooled sensitivity of 0.638 (95% CI 0.511 to 0.748), specificity of 0.801 (95% CI 0.691 to 0.878) and AUC of 0.79 (95% CI 0.75 to 0.82). Our results indicate that breath test is a promising approach with acceptable diagnostic accuracy for diabetes mellitus and isotopic CO is the optimal breath biomarker. Even so, further validation and standardization in subject control, breath sampling and analysis are still required.
Topics: Biomarkers; Breath Tests; Diabetes Mellitus, Type 2; Humans; Reference Standards
PubMed: 34031142
DOI: 10.1136/bmjdrc-2021-002174 -
Molecules (Basel, Switzerland) Sep 2021The detection of chemical compounds in exhaled human breath presents an opportunity to determine physiological state, diagnose disease or assess environmental exposure.... (Review)
Review
The detection of chemical compounds in exhaled human breath presents an opportunity to determine physiological state, diagnose disease or assess environmental exposure. Recent advancements in metabolomics research have led to improved capabilities to explore human metabolic profiles in breath. Despite some notable challenges in sampling and analysis, exhaled breath represents a desirable medium for metabolomics applications, foremost due to its non-invasive, convenient and practically limitless availability. Several breath-based tests that target either endogenous or exogenous gas-phase compounds are currently established and are in practical and/or clinical use. This review outlines the concept of breath analysis in the context of these unique tests and their applications. The respective breath biomarkers targeted in each test are discussed in relation to their physiological production in the human body and the development and implementation of the associated tests. The paper concludes with a brief insight into prospective tests and an outlook of the future direction of breath research.
Topics: Biomarkers; Breath Tests; Chemistry Techniques, Analytical; Exhalation; Humans; Metabolomics; Volatile Organic Compounds
PubMed: 34576985
DOI: 10.3390/molecules26185514 -
Journal of Hematology & Oncology Jun 2023Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC...
BACKGROUND
Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear.
METHODS
This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts.
RESULTS
A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts.
CONCLUSIONS
This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.
Topics: Humans; Female; Breast Neoplasms; Volatile Organic Compounds; Cohort Studies; Early Detection of Cancer; Breath Tests; Biopsy
PubMed: 37328852
DOI: 10.1186/s13045-023-01459-9