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European Surgical Research. Europaische... 2023The potential for exhaled breath to be a valuable diagnostic tool is often overlooked as it can be difficult to imagine how a barely visible sample of breath could hold... (Review)
Review
BACKGROUND
The potential for exhaled breath to be a valuable diagnostic tool is often overlooked as it can be difficult to imagine how a barely visible sample of breath could hold such a rich source of information about the state of our health. However, technological advances over the last 50 years have enabled us to detect volatile organic compounds (VOCs) present in exhaled breath, and this provides the key to understanding the wealth of information contained within these readily available samples.
SUMMARY
VOCs are produced as a by-product of metabolism; hence, changes in the underlying physiological processes will be reflected in the exact composition of VOCs in exhaled breath. It has been shown that characteristic changes occur in the breath VOC profile associated with certain diseases including cancer, which may enable the non-invasive detection of cancer at primary care level for patients with vague symptoms. The use of breath testing as a diagnostic tool has many advantages. It is non-invasive and quick, and the test is widely accepted by patients and clinicians. However, breath samples provide a snapshot of the VOCs present in a particular patient at a given point in time, so this can be heavily influenced by external factors such as diet, smoking, and the environment. These must all be accounted for when attempting to draw conclusions about disease status. This review focuses on the current applications for breath testing in the field of surgery, as well as discussing the challenges encountered with developing a breath test in a clinical environment. The future of breath testing in the surgical setting is also discussed, including the translation of breath research into clinical practice.
KEY MESSAGES
Analysis of VOCs in exhaled breath can identify the presence of underlying disease including cancer as well as other infectious or inflammatory conditions. Despite the patient factors, environmental factors, storage, and transport considerations that must be accounted for, breath testing demonstrates ideal characteristics for a triage test, being non-invasive, simple, and universally acceptable to patients and clinicians. Many novel biomarkers and diagnostic tests fail to translate into clinical practice because their potential clinical application does not align with the requirements and unmet needs of the healthcare sector. Non-invasive breath testing, however, has the great potential to revolutionise the early detection of diseases, such as cancer, in the surgical setting for patients with vague symptoms.
Topics: Humans; Biomarkers; Neoplasms; Breath Tests; Volatile Organic Compounds; Exhalation
PubMed: 37311421
DOI: 10.1159/000531504 -
BMC Public Health Apr 2023The prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
The ADEM2 project: early pathogenic mechanisms of preschool wheeze and a randomised controlled trial assessing the gain in health and cost-effectiveness by application of the breath test for the diagnosis of asthma in wheezing preschool children.
BACKGROUND
The prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof-MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children.
METHODS
This study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath.
DISCUSSION
The potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies.
TRIAL REGISTRATION
Netherlands Trial Register, NL7336, Date registered 11-10-2018.
Topics: Humans; Child, Preschool; Child; Volatile Organic Compounds; Respiratory Sounds; Cost-Benefit Analysis; Asthma; Breath Tests
PubMed: 37013496
DOI: 10.1186/s12889-023-15465-6 -
World Journal of Gastroenterology Aug 2019Liver disease is characterized by breath exhalation of peculiar volatile organic compounds (VOCs). Thanks to the availability of sensitive technologies for breath...
Liver disease is characterized by breath exhalation of peculiar volatile organic compounds (VOCs). Thanks to the availability of sensitive technologies for breath analysis, this empiric approach has recently gained increasing attention in the context of hepatology, following the good results obtained in other fields of medicine. After the first studies that led to the identification of selected VOCs for pathophysiological purposes, subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application. Specific VOC patterns were found to discriminate subjects with liver cirrhosis, to rate disease severity, and, eventually, to forecast adverse clinical outcomes even beyond existing scores. Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease. However, clinical translation is still hampered by a number of methodological limitations, including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results. Given the low-cost and easy execution at bedside of the new technologies (e-nose), larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.
Topics: Breath Tests; Electronic Nose; Exhalation; Gastroenterology; Humans; Liver Diseases; Volatile Organic Compounds
PubMed: 31435162
DOI: 10.3748/wjg.v25.i30.4043 -
Polski Przeglad Chirurgiczny Jun 2018Helicobacter pylori (Hp) is classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen. Its influence on the carcinogenesis of gastric... (Comparative Study)
Comparative Study
BACKGROUND
Helicobacter pylori (Hp) is classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen. Its influence on the carcinogenesis of gastric cancer has been confirmed in many researches. The conclusion is obvious- early detection and eradication of Hp can prevent the development of the disease.
METHODS
The objective of the study was to analyse the clinical and practical value of Carbon-13 urea breath test (UBT) in patients hospitalized due to pain complaints in the upper abdomen and dyspeptic symptoms. Fifty patients were enrolled in the study. Each patient underwent urea breath test according to the instruction included by the producer. Thereafter, each patient included in the study group was performed endoscopy of the upper gastrointestinal tract with the biopsy of the mucosa to determine the urease activity with rapid urease test (RUT).
RESULTS
In the study group, 14 patients (28%) achieved a positive urease test result which was confirmed in RUT. Four (8%) patients, despite a positive breath test, did not have a positive result in urease activity from gastric mucosa. In 2 cases (4%) despite negative result of UBT there was urease actitvity confirmed in gastroscopic sections. The remaining 30 patients (60%) had a negative result in both studies.
CONCLUSIONS
The limited availability of the gold standard for diagnostics of upper gastrointestinal tract diseases (gastroscopy) is the basis for the search for new methods for the detection of Helicobacter pylori infection. The urea breath test is a method of high sensitivity and specificity. The positive result of urea breath test may be the basis for the inclusion of eradication therapy.
Topics: Adult; Aged; Breath Tests; Early Diagnosis; Endoscopy; Female; Helicobacter Infections; Humans; Male; Middle Aged; Sensitivity and Specificity; Urea; Urease; Young Adult
PubMed: 30426947
DOI: 10.5604/01.3001.0012.0669 -
International Journal of Environmental... Aug 2022Dairy products are frequently considered responsible for post-prandial symptoms and are withdrawn from the diet, even against medical advice. We analysed the symptoms...
Dairy products are frequently considered responsible for post-prandial symptoms and are withdrawn from the diet, even against medical advice. We analysed the symptoms patients consider as lactose related; we also evaluated if psychological profile may affect the interpretation of the relationship between lactose and symptoms. In 268 patients undergoing lactose breath test, symptoms considered evoked by lactose intake were recorded and their severity measured. In the second part, symptom onset of 40 randomly selected patients was detected after both lactose and glucose breath test were blindly performed. Questionnaires evaluating anxiety, suggestibility and personality trait were administered. : Symptoms depending on functional gastrointestinal disorders or reflux disease were frequent in self-reported lactose-intolerant patients. In comparison with lactose malabsorption, these symptoms proved to be more frequent in patients with negative lactose breath test. The blinded administration of lactose and glucose demonstrated that a correct link between lactose intake and symptom onset was possible, only in 47.5% of the subjects, making this test inaccurate. None of the investigated psychological characteristics were different between patients with a nocebo response and patients not experiencing nocebo. : Patients with self-reported lactose intolerance are frequently unaware about clinical presentation of this condition, and correct information is needed. The detection of symptom onset after lactose is an inaccurate test for lactose intolerance. Furthermore, the analysis of psychological characteristics of patients undergoing hydrogen breath test is not useful to select the subgroup at risk for a nocebo response. New strategies to diagnose lactose intolerance are mandatory.
Topics: Breath Tests; Glucose; Humans; Lactose; Lactose Intolerance; Perception
PubMed: 36011869
DOI: 10.3390/ijerph191610234 -
Journal of Breath Research Nov 2022Measuring the concentration of alcohol (ethanol) in exhaled breath (BrAC) provides a rapid and non-invasive way to determine the co-existing concentration in arterial... (Review)
Review
Measuring the concentration of alcohol (ethanol) in exhaled breath (BrAC) provides a rapid and non-invasive way to determine the co-existing concentration in arterial blood (A-BAC). The results of breath-alcohol testing are used worldwide as evidence of excessive drinking, such as when traffic offenders are prosecuted. Two types of breath-alcohol analyzer are in common use; hand-held instruments used as preliminary screening tests of sobriety and more sophisticated evidential instruments, the results of which are accepted as evidence for prosecution of drunken drivers. Most evidential breath-alcohol analyzers are designed to capture the last portion of a prolonged exhalation, which is thought to reflect the alcohol concentration in substantially alveolar air. The basic premise of breath-alcohol analysis is that there is a physiological relationship between A-BAC and BrAC and close agreement between the two analytical methods. This article reviews the principles and practice of breath-alcohol analysis and introduces the concept of standardizing the results to a secondary physiological gas (water vapor), which therefore serves as an internal standard. The measured BrAC is thus adjusted to an alveolar air water content of 43.95 mg lat 37 °C. This has several advantages, and means that a sample of breath can be captured without the person having to blow directly into the instrument. Adjusting the breath-alcohol concentration to water vapor concentration also compensates for variations in temperature of the expired air. The contact-free method of sampling breath means that a mouthpiece is unnecessary and the test subject does not need to make a continuous end exhalation.
Topics: Humans; Exhalation; Breath Tests; Steam; Ethanol
PubMed: 36368034
DOI: 10.1088/1752-7163/aca21b -
Oncotarget Nov 2015Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of... (Review)
Review
BACKGROUND
Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of adherence at virtually no risk in population-based screening. In this review, we summarize the current evidence of exhaled breath analysis for cancer detection using standard analysis techniques and electronic nose.
METHODS
Relevant studies were identified searching Pubmed and Web of Science databases until April 30, 2015. Information on breath test performance, such as sensitivity and specificity, was extracted together with volatile compounds that were used to discriminate cancer patients from controls. Performance of different breath analysis techniques is provided for various cancers together with information on methodological issues, such as breath sampling protocol and validation of the results.
RESULTS
Overall, 73 studies were included, where two-thirds of the studies were conducted on lung cancer. Good discrimination usually required a combination of multiple biomarkers, and area under the receiver operating characteristic curve or accuracy reached levels of 0.9 or higher in multiple studies. In 25% of the reported studies, classification models were built and validated on the same datasets. Huge variability was seen in different aspects among the studies.
CONCLUSIONS
Analyses of exhaled breath yielded promising results, although standardization of breath collection, sample storage and data handling remain critical issues. In order to foster breath analysis implementation into practice, larger studies should be implemented in true screening settings, paying particular attention to standardization in breath collection, consideration of covariates, and validation in independent population samples.
Topics: Biomarkers, Tumor; Breath Tests; Exhalation; Humans; Lung Neoplasms
PubMed: 26440312
DOI: 10.18632/oncotarget.5938 -
Current Oncology (Toronto, Ont.) Sep 2022Breath analysis is a promising non-invasive method for the detection and management of lung cancer. Exhaled breath contains a complex mixture of volatile and... (Review)
Review
Breath analysis is a promising non-invasive method for the detection and management of lung cancer. Exhaled breath contains a complex mixture of volatile and non-volatile organic compounds that are produced as end-products of metabolism. Several studies have explored the patterns of these compounds and have postulated that a unique breath signature is emitted in the setting of lung cancer. Most studies have evaluated the use of gas chromatography and mass spectrometry to identify these unique breath signatures. With recent advances in the field of analytical chemistry and machine learning gaseous chemical sensing and identification devices have also been created to detect patterns of odorant molecules such as volatile organic compounds. These devices offer hope for a point-of-care test in the future. Several prospective studies have also explored the presence of specific genomic aberrations in the exhaled breath of patients with lung cancer as an alternative method for molecular analysis. Despite its potential, the use of breath analysis has largely been limited to translational research due to methodological issues, the lack of standardization or validation and the paucity of large multi-center studies. It is clear however that it offers a potentially non-invasive alternative to investigations such as tumor biopsy and blood sampling.
Topics: Humans; Breath Tests; Complex Mixtures; Lung Neoplasms; Prospective Studies; Volatile Organic Compounds
PubMed: 36290855
DOI: 10.3390/curroncol29100578 -
European Review For Medical and... 2013Orocecal transit time (OCTT) is one of the main determinant of the hunger ratings and gastrointestinal sensitivity. While marked-isotopes scintigraphy is the gold... (Review)
Review
Orocecal transit time (OCTT) is one of the main determinant of the hunger ratings and gastrointestinal sensitivity. While marked-isotopes scintigraphy is the gold standard in its determination in the clinical frame, breath tests are cheap, well-tolerated and non-invasive alternatives. In fact C-13 and C-14 stable isotopes breath tests can be used to assess gastric emptying and OCTT in the clinical and research frames. Moreover, hydrogen (H2) lactulose breath test can be used to assess OCTT in the research frame only due to its laxative action; inulin breath test, devoid of this bias, could be replacing it. However, the main limitation in the use of breath tests in the OCTT determination is their low reproducibility.
Topics: Animals; Biomarkers; Breath Tests; Gases; Gastric Emptying; Gastrointestinal Diseases; Gastrointestinal Transit; Humans; Inulin; Lactulose; Predictive Value of Tests; Reproducibility of Results; Time Factors
PubMed: 24443067
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Oct 2013Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Small intestinal bacterial overgrowth (SIBO) is an under-recognised diagnosis with important clinical implications when untreated. However, the optimal treatment regimen remains unclear.
AIM
To perform a systematic review and meta-analysis comparing the clinical effectiveness of antibiotic therapies in the treatment of symptomatic patients with documented SIBO.
METHODS
Four databases were searched to identify clinical trials comparing effectiveness of: (i) different antibiotics, (ii) different doses of the same antibiotic and (iii) antibiotics compared with placebo. Data were independently extracted according to predetermined inclusion and exclusion criteria. Study quality was independently assessed. The primary outcome was normalisation of post-treatment breath testing. The secondary outcome was post-treatment clinical response.
RESULTS
Of 1356 articles identified, 10 met inclusion criteria. Rifaximin was the most commonly studied antibiotic (eight studies) with overall breath test normalisation rate of 49.5% (95% confidence interval, CI 44.0-55.1) (44.0%-55.1%) then (46.7%-55.5%), then (4.6%-17.8%). Antibiotic efficacy varied by antibiotic regimen and dose. Antibiotics were more effective than placebo, with a combined breath test normalisation rate of 51.1% (95% CI 46.7-55.5) for antibiotics compared with 9.8% (95% CI 4.6-17.8) for placebo. Meta-analysis of four studies favoured antibiotics over placebo for breath test normalisation with an odds ratio of 2.55 (95% CI 1.29-5.04). Clinical response was heterogeneously evaluated among six studies, but tended to correlate with breath test normalisation.
CONCLUSIONS
Antibiotics appear to be more effective than placebo for breath test normalisation in patients with symptoms attributable to SIBO, and breath test normalisation may correlate with clinical response. Studies were limited by modest quality, small sample size and heterogeneous design. Additional higher quality clinical trials of SIBO therapy are warranted.
Topics: Anti-Bacterial Agents; Bacterial Infections; Breath Tests; Humans; Intestine, Small; Rifamycins; Rifaximin
PubMed: 24004101
DOI: 10.1111/apt.12479