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Scientific Reports Oct 2022Being the proximal matrix, breath offers immediate metabolic outlook of respiratory infections. However, high viral load in exhalations imposes higher transmission risk...
Being the proximal matrix, breath offers immediate metabolic outlook of respiratory infections. However, high viral load in exhalations imposes higher transmission risk that needs improved methods for safe and repeatable analysis. Here, we have advanced the state-of-the-art methods for real-time and offline mass-spectrometry based analysis of exhaled volatile organic compounds (VOCs) under SARS-CoV-2 and/or similar respiratory conditions. To reduce infection risk, the general experimental setups for direct and offline breath sampling are modified. Certain mainstream and side-stream viral filters are examined for direct and lab-based applications. Confounders/contributions from filters and optimum operational conditions are assessed. We observed immediate effects of infection safety mandates on breath biomarker profiles. Main-stream filters induced physiological and analytical effects. Side-stream filters caused only systematic analytical effects. Observed substance specific effects partly depended on compound's origin and properties, sampling flow and respiratory rate. For offline samples, storage time, -conditions and -temperature were crucial. Our methods provided repeatable conditions for point-of-care and lab-based breath analysis with low risk of disease transmission. Besides breath VOCs profiling in spontaneously breathing subjects at the screening scenario of COVID-19/similar test centres, our methods and protocols are applicable for moderately/severely ill (even mechanically-ventilated) and highly contagious patients at the intensive care.
Topics: Humans; Volatile Organic Compounds; COVID-19; SARS-CoV-2; Breath Tests; Exhalation; Biomarkers; Monitoring, Physiologic
PubMed: 36289276
DOI: 10.1038/s41598-022-22581-7 -
Gut Jul 1999The urea breath test (UBT) is one of the most important non-invasive methods for detecting Helicobacter pylori infection. The test exploits the hydrolysis of orally... (Review)
Review
The urea breath test (UBT) is one of the most important non-invasive methods for detecting Helicobacter pylori infection. The test exploits the hydrolysis of orally administered urea by the enzyme urease, which H pylori produces in large quantities. Urea is hydrolysed to ammonia and carbon dioxide, which diffuses into the blood and is excreted by the lungs. Isotopically labelled CO2 can be detected in breath using various methods. Labelling urea with 13C is becoming increasingly popular because this non-radioactive isotope is innocuous and can be safely used in children and women of childbearing age. Breath samples can also be sent by post or courier to remote analysis centres. The test is easy to perform and can be repeated as often as required in the same patient. A meal must be given to increase the contact time between the tracer and the H pylori urease inside the stomach. The test has been simplified to the point that two breath samples collected before and 30 minutes after the ingestion of urea in a liquid form suffice to provide reliable diagnostic information. The cost of producing 13C-urea is high, but it may be possible to reduce the dosage further by administering it in capsule form. An isotope ratio mass spectrometer (IRMS) is generally used to measure 13C enrichment in breath samples, but this machine is expensive. In order to reduce this cost, new and cheaper equipment based on non-dispersive, isotope selective, infrared spectroscopy (NDIRS) and laser assisted ratio analysis (LARA) have recently been developed. These are valid alternatives to IRMS although they cannot process the same large number of breath samples simultaneously. These promising advances will certainly promote the wider use of the 13C-UBT, which is especially useful for epidemiological studies in children and adults, for screening patients before endoscopy, and for assessing the efficacy of eradication regimens.
Topics: Breath Tests; Carbon Radioisotopes; Helicobacter Infections; Helicobacter pylori; Humans; Urea
PubMed: 10457031
DOI: 10.1136/gut.45.2008.i18 -
United European Gastroenterology Journal Jun 2021C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the... (Review)
Review
European guideline on indications, performance and clinical impact of C-breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC.
INTRODUCTION
C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers.
METHODS
This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed.
RESULTS
The guideline gives an overview over general methodology of C-breath testing and provides recommendations for the use of C-breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of C-breath testing are summarized briefly. The recommendations specifically detail when and how individual C-breath tests should be performed including examples for well-established test protocols, patient preparation, and reporting of test results.
CONCLUSION
This clinical practice guideline should improve 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, this guideline identifies areas of future clinical research involving the use of C-breath tests.
Topics: Adult; Breath Tests; Carbon Isotopes; Child; Consensus; Delphi Technique; Europe; Gastric Emptying; Helicobacter Infections; Helicobacter pylori; Humans; Liver; Liver Function Tests; Pancreas, Exocrine; Pancreatic Function Tests; Urea
PubMed: 34128346
DOI: 10.1002/ueg2.12099 -
Scientific Reports Jan 2021The measurement of hydrogen-methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering...
The measurement of hydrogen-methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering breath testing provide variable guidance regarding oral hygiene practices prior to testing. Given that oral dysbiosis has the potential to cause changes in breath gases, it raises concerns that oral hygiene is not a standard inclusion in current breath testing guidelines. The aim of this study was to determine how a pre-test mouthwash may impact hydrogen-methane breath test results. Participants presenting for breath testing who had elevated baseline gases were given a chlorhexidine mouthwash. If a substantial reduction in expired hydrogen or methane occurred after the mouthwash, breath samples were collected before and after a mouthwash at all breath sample collection points for the duration of testing. Data were evaluated to determine how the mouthwash might influence test results and diagnostic status. In 388 consecutive hydrogen-methane breath tests, modifiable elevations occurred in 24.7%. Administration of a chlorhexidine mouthwash resulted in significantly (p ≤ 0.05) reduced breath hydrogen in 67% and/or methane gas in 93% of those consenting to inclusion. In some cases, this modified the diagnosis. Mean total gas concentrations pre- and post-mouthwash were 221.0 ppm and 152.1 ppm (p < 0.0001) for hydrogen, and 368.9 ppm and 249.8 ppm (p < 0.0001) for methane. Data suggest that a single mouthwash at baseline has a high probability of returning a false positive diagnosis. Variations in gas production due to oral hygiene practices has significant impacts on test interpretation and the subsequent diagnosis. The role of oral dysbiosis in causing gastrointestinal symptoms also demands exploration as it may be an underlying factor in the presenting condition that was the basis for the referral.
Topics: Adolescent; Adult; Aged; Breath Tests; Dysbiosis; Exhalation; Female; Gases; Gastrointestinal Diseases; Humans; Hydrogen; Malabsorption Syndromes; Male; Methane; Middle Aged; Mouthwashes; Oral Hygiene; Young Adult
PubMed: 33420116
DOI: 10.1038/s41598-020-79554-x -
Expert Opinion on Therapeutic Patents Dec 2016Stable isotope breath tests can rapidly and quantitatively report metabolic phenotypes and disease in both humans and microbes in situ. The labelled compound is... (Review)
Review
Stable isotope breath tests can rapidly and quantitatively report metabolic phenotypes and disease in both humans and microbes in situ. The labelled compound is administered and acted upon by human or microbial metabolism, producing a labelled gas that is detected in exhaled breath. Areas covered: This review details the unique advantages (and disadvantages) of phenotypic stable isotope based breath tests. A review of recent US patent applications and prosecutions since 2010 is conducted. Finally, current clinical trials, product pipelines and approved products are discussed. Expert opinion: Stable isotope breath tests offer new approaches for rapid and minimally invasive detection and study of metabolic phenotypes, both human and microbial. The patent literature has developed considerably in the last 6 years, with over 30 patent applications made. Rates of issuance remain high, although rejections citing 35 U.S.C. §101(subject matter eligibility), §102 (novelty), §103 (obviousness) and §112 (description, enablement and best mode) have occurred. The prior art is significantly greater for human metabolism than microbial, and may drive differing rates of future issuance. These biomarker and diagnostic tools can enable optimization of drug doses, diagnosis of metabolic disease and its progression, and detection of infectious disease and optimize its treatment.
Topics: Biomarkers; Breath Tests; Communicable Diseases; Disease Progression; Humans; Isotopes; Metabolic Diseases; Patents as Topic; Phenotype
PubMed: 27467014
DOI: 10.1080/13543776.2016.1217995 -
International Journal of Molecular... Aug 2022Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria,... (Review)
Review
Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.
Topics: Adult; Biomarkers; Breath Tests; C-Reactive Protein; Cytokines; Exhalation; Humans; Inflammation
PubMed: 36077213
DOI: 10.3390/ijms23179820 -
Annals of Medicine Dec 2022The clinical application of lung cancer detection based on breath test is still challenging due to lack of predictive molecular markers in exhaled breath. This study...
INTRODUCTION
The clinical application of lung cancer detection based on breath test is still challenging due to lack of predictive molecular markers in exhaled breath. This study explored potential lung cancer biomarkers and their related pathways using a typical process for metabolomics investigation.
MATERIAL AND METHODS
Breath samples from 60 lung cancer patients and 176 healthy people were analyzed by GC-MS. The original data were GC-MS peak intensity removing background signal. Differential metabolites were selected after univariate statistical analysis and multivariate statistical analysis based on OPLS-DA and Spearman rank correlation analysis. A multivariate PLS-DA model was established based on differential metabolites for pattern recognition. Subsequently, pathway enrichment analysis was performed on differential metabolites.
RESULTS
The discriminant capability was assessed by ROC curve of whom the average AUC and average accuracy in 100-fold cross validations were 0.871 and 0.787, respectively. Eight potential biomarkers were involved in a total of 18 metabolic pathways. Among them, 11 metabolic pathways have -value smaller than .1.
DISCUSSION
Some pathways among them are related to risk factors or therapies of lung cancer. However, more of them are dysregulated pathways of lung cancer reported in studies based on genome or transcriptome data.
CONCLUSION
We believe that it opens the possibility of using metabolomics methods to analyze data of exhaled breath and promotes involvement of knowledge dataset to cover more volatile metabolites.
CLINICAL SIGNIFICANCE
Although a series of related research reported diagnostic models with highly sensitive and specific prediction, the clinical application of lung cancer detection based on breath test is still challenging due to disease heterogeneity and lack of predictive molecular markers in exhaled breath. This study may promote the clinical application of this technique which is suitable for large-scale screening thanks to its low-cost and non-invasiveness. As a result, the mortality of lung cancer may be decreased in future.Key messagesIn the present study, 11 pathways involving 8 potential biomarkers were discovered to be dysregulated pathways of lung cancer.We found that it is possible to apply metabolomics methods in analysis of data from breath test, which is meaningful to discover convinced volatile markers with definite pathological and histological significance.
Topics: Biomarkers, Tumor; Breath Tests; Gas Chromatography-Mass Spectrometry; Humans; Lung Neoplasms; Pilot Projects
PubMed: 35261323
DOI: 10.1080/07853890.2022.2048064 -
The Indian Journal of Medical Research May 2012Tuberculosis (TB) remains a significant public health issue worldwide especially in developing countries, where the disease is endemic, and effective TB diagnostic as... (Review)
Review
Tuberculosis (TB) remains a significant public health issue worldwide especially in developing countries, where the disease is endemic, and effective TB diagnostic as well as treatment-monitoring tools are serious barriers to defeating the disease. Detection of pathogen-specific metabolic pathways offers a potential alternative to current methods, which focus on bacterial growth, bacterial nucleic acid amplification, or detection of host immune response to the pathogen. Metabolic pathway detection may provide rapid and effective new tools for TB that can improve TB diagnostics for children and HIV infected patients. Metabolic breath tests are attractive because these are safe, and provide an opportunity for rapid point of care diagnostics and tool for drug efficacy evaluation during clinical trials. Our group has developed a rabbit urease breath test model to evaluate the sensitivity and the specificity of urease based detection of Mycobacterium tuberculosis. TB infected rabbits were given stable isotopically labelled urea as the substrate. The urea tracer was metabolized to 13 C-CO 2 and detected in exhaled breaths using portable infrared spectrometers. The signal correlated with bacterial load both for primary diagnostics and treatment monitoring. Clinical trials are currently ongoing to evaluate the value of the test in clinical management settings. Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and treatment response.
Topics: Animals; Breath Tests; Carbon Dioxide; Carbon Radioisotopes; Clinical Trials as Topic; Disease Models, Animal; Helicobacter pylori; Humans; Mycobacterium tuberculosis; Rabbits; Tuberculosis; Urease
PubMed: 22771606
DOI: No ID Found -
Journal of Pediatric Gastroenterology... Jun 2018Human starch digestion is a multienzyme process involving 6 different enzymes: salivary and pancreatic α-amylase; sucrase and isomaltase (from sucrose-isomaltase [SI]),...
BACKGROUND AND HYPOTHESES
Human starch digestion is a multienzyme process involving 6 different enzymes: salivary and pancreatic α-amylase; sucrase and isomaltase (from sucrose-isomaltase [SI]), and maltase and glucoamylase (from maltase-glucoamylase [MGAM]). Together these enzymes cleave starch to smaller molecules ultimately resulting in the absorbable monosaccharide glucose. Approximately 80% of all mucosal maltase activity is accounted for by SI and the reminder by MGAM. Clinical studies suggest that starch may be poorly digested in those with congenital sucrase-isomaltase deficiency (CSID). Poor starch digestion occurs in individuals with CSID and can be documented using a noninvasive C-breath test (BT).
METHODS
C-Labled starch was used as a test BT substrate in children with CSID. Sucrase deficiency was previously documented in study subjects by both duodenal biopsy enzyme assays and C-sucrose BT. Breath CO2 was quantitated at intervals before and after serial C-substrate loads (glucose followed 75 minutes later by starch). Variations in metabolism were normalized against C-glucose BT (coefficient of glucose absorption). Control subjects consisted of healthy family members and a group of children with functional abdominal pain with biopsy-proven sucrase sufficiency.
RESULTS
Children with CSID had a significant reduction of C-starch digestion mirroring that of their duodenal sucrase and maltase activity and C-sucrase BT.
CONCLUSIONS
In children with CSID, starch digestion may be impaired. In children with CSID, starch digestion correlates well with measures of sucrase activity.
Topics: Adolescent; Breath Tests; Carbohydrate Metabolism, Inborn Errors; Carbon Isotopes; Case-Control Studies; Child; Child, Preschool; Digestion; Duodenum; Female; Humans; Infant; Male; Starch; Sucrase-Isomaltase Complex
PubMed: 29762381
DOI: 10.1097/MPG.0000000000001858 -
BMJ Open Gastroenterology Jul 2021Clinical data comparing diagnostic strategies in the management of -associated diseases are limited. Invasive and noninvasive diagnostic tests for detecting infection...
OBJECTIVE
Clinical data comparing diagnostic strategies in the management of -associated diseases are limited. Invasive and noninvasive diagnostic tests for detecting infection are used in the clinical care of patients with dyspeptic symptoms. Modelling studies might help to identify the most cost-effective strategies. The objective of the study is to assess the cost-effectiveness of a 'test-and-treat' strategy with the urea breath test (UBT) compared with other strategies, in managing patients with -associated dyspepsia and preventing peptic ulcer in the UK.
DESIGN
Cost-effectiveness models compared four strategies: 'test-and-treat' with either UBT or faecal antigen test (FAT), 'endoscopy-based strategy' and 'symptomatic treatment'. A probabilistic cost-effectiveness analysis was performed using a simulation model in order to identify probabilities and costs associated with relief of dyspepsia symptoms (over a 4-week time horizon) and with prevention of peptic ulcers (over a 10-year time horizon). Clinical and cost inputs to the model were derived from routine medical practice in the UK.
RESULTS
For relief of dyspepsia symptoms, 'test-and-treat' strategies with either UBT (€526/success) and FAT (€518/success) were the most cost-effective strategies compared with 'endoscopy-based strategy' (€1317/success) and 'symptomatic treatment' (€1 029/success). For the prevention of peptic ulcers, 'test-and-treat' strategies with either UBT (€208/ulcer avoided/year) or FAT (€191/ulcer avoided/year) were the most cost-effective strategies compared with 'endoscopy-based strategy' (€717/ulcer avoided/year) and 'symptomatic treatment' (€651/ulcer avoided/year) (1 EUR=0,871487 GBP at the time of the study).
CONCLUSION
'Test-and-treat' strategies with either UBT or FAT are the most cost-effective medical approaches for the management of -associated dyspepsia and the prevention of peptic ulcer in the UK. A 'test-and-treat' strategy with UBT has comparable cost-effectiveness outcomes to the current standard of care using FAT in the UK.
Topics: Breath Tests; Cost-Benefit Analysis; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; United Kingdom; Urea
PubMed: 34244244
DOI: 10.1136/bmjgast-2021-000685