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Schematic diagram of the residual gas analyzer mass spectrometry (RGA-MS) system. TMP: turbo molecular pump; AMLV: all-metal leak valve.
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A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through (13)C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision (13)CO2 isotope enrichments in exhaled breath samples from indivi...
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... schematic diagram of the RGA (Prisma Plus, PT-M05-212- 111, Pfeiffer vacuum, 1-200 amu) coupled with a customized HV cylindrical chamber for measuring exhaled breath samples is depicted in figure 1. The typical baseline vacuum level in the HV chamber was ∼ 9.5 × 10 −8 Torr (1 Torr = 1.33 mbar). ...
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Exhaled breath analysis for early disease detection may provide a convenient method for painless and non-invasive diagnosis. In this work, a novel, compact and easy-to-use breath analyzer platform with a modular sensing chamber and direct breath sampling unit is presented. The developed analyzer system comprises a compact, low volume, temperature-c...
Citations
... However, in recent years, a simple residual gas analyzer (RGA)-based mass-spectrometry (MS) technique was employed for real-time breath analysis, which is also well-suited for non-invasive diagnosis of H. pylori bacterial infection. 22 We have utilized such an RGA-based concept as a non-invasive detection method that recognizes the mass-selective breathograms and unique breath patterns that reflect the specific gastric condition of an individual person. Therefore, the novel insight here is that the exact identification of the individual or multiple molecular species in exhaled breath is not mandatory for the diagnosis and classifications. ...
... The clinical validation of the residual gas analyzer (RGA)-based MS system for real-time exhaled breath analysis as well as the non-invasive diagnosis of H. pylori infection has been described elaborately elsewhere. 22 In brief, the system consists of a compact and specially designed breath gas chamber coupled with a high vacuum (∼10 −9 Torr) which is maintained by two turbo-molecular pumps backed up with a diaphragm pump. A residual gas analyzer (RGA) (QMG 220 M1, PrismaPlus, Pfeiffer Vacuum, mass range: 1-100 amu) that exploits a conventional quadrupole mass filter technology is connected with the gas chamber. ...
... To give a context, it is noteworthy to mention that the bacterial infection of H. pylori is medically recognized as one of the prime causes of the different gastric disorders, and 13 C-UBT is a widely accepted non-invasive methodology for the diagnosis of H. pylori infection using exhaled breath analysis. 22 Here, the proposed methodology of BPs has been shown to address the current limitations of the existed 13 C-UBT. Figure 6 illustrates such a situation exploiting the signature of a BP where the patients have various gastric disorders irrespective of whether the patient is harboring H. pylori infection or not in the stomach. ...
Conventional endoscopic biopsy tests are not suitable for early detection of the acute onset and progression of peptic ulcer as well as various gastric complications. This also limits its suitability for widespread population-based screening and consequently, many people with complex gastric phenotypes remain undiagnosed. Here, we demonstrate a new non-invasive methodology for accurate diagnosis and classification of various gastric disorders exploiting a pattern-recognition-based cluster analysis of a breathomics dataset generated from a simple residual gas analyzer-mass spectrometry. The clustering approach recognizes unique breathograms and “breathprints” signatures that clearly reflect the specific gastric condition of an individual person. The method can selectively distinguish the breath of peptic ulcer and other gastric dysfunctions like dyspepsia, gastritis, and gastroesophageal reflux disease patients from the exhaled breath of healthy individuals with high diagnostic sensitivity and specificity. Moreover, the clustering method exhibited a reasonable power to selectively classify the early-stage and high-risk gastric conditions with/without ulceration, thus opening a new non-invasive analytical avenue for early detection, follow-up, and fast population-based robust screening strategy of gastric complications in the real-world clinical domain.
... The methods used in these studies were ranked according to World Gastroenterology Organization global guidelines based Urease [19,23,24,29,32,33,35,39,40,42,44,46,50,51,52,53,54,55,57,59,63,64,65,67,70,72,78 [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,85]. p**; One-Way ANOVA, NA; Non Aplicated, ***; Calculations were conducted according to data compatibility, incompatible studies excluded. ...
... The methods used in these studies were ranked according to World Gastroenterology Organization global guidelines based Urease [19,23,24,29,32,33,35,39,40,42,44,46,50,51,52,53,54,55,57,59,63,64,65,67,70,72,78 [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,85]. p**; One-Way ANOVA, NA; Non Aplicated, ***; Calculations were conducted according to data compatibility, incompatible studies excluded. ...
Study Aims: The purpose of this study was to evaluate the test preferences for Helicobacter pylori detection in developing countries. Patients and methods: A systematic search of PubMed, Web of Science, EMBASE, ClinicalTrials.Gov, OVID, and the Cochran Library databases was performed to identify relevant review articles, editorials, and original studies published in the English language using the following. Results: Sufficient information was available to pool data from 67 randomized trials for meta-analyses. Non-invasive diagnostic methods, including the stool antigen test, were used in three studies to determine H. pylori infection. Another 64 (96%) studies were designed with invasive tests to address diagnoses related to H. pylori infection. The enzyme-linked immunosorbent assay method was used in 21 (32.3%) studies. Diagnostic processes in another 44 studies were performed with endoscopic biopsy specimens. Culture results were reported only in two studies with histopathology, and molecular test results were discussed in six studies, whereas histopathology results were given in only six studies. A significant difference in H. pylori positivity was found among countries. Conclusions: In light of these results, it will be important to address the following question: Which test is best for H. pylori diagnosis in developing countries? This is a complicated question, but changing H. pylori testing policies in developing countries is urgently needed to grant better access to service. Future studies should focus on clarifying which test is more appropriate for patients with an H. pylori infection while taking into account clinical characteristics, pre-infection status, and availability and cost.
... For all the enrolled individuals, there was no contradiction between the test reports of H. pylori infection of both tests. In 13 C-UBT, individuals with the value of δ DOB 13 C (‰) ≥ 3 ‰ at 30 min were considered to be H. pylori positive [9,10,19]. Patients receiving antibiotics, proton pump inhibitors or H 2 receptor antagonists 4 weeks prior to the study were excluded at the initial screening. The Ethics Committee Review Board of AMRI Hospital, Salt Lake, Kolkata, India, approved the protocol of the current study (Study no.: AMRI/ETHICS/2013/1). ...
... A CO 2 isotope analyser (CCIA 36-EP, LGR, USA) exploiting off-axis ICOS was utilized for extremely precise measurements of 12 CO 2 , 13 CO 2 and 12 C 16 O 18 O isotopes of CO 2 in a gas sample. The details of the ICOS system and its capability for high precision isotope measurements were described elsewhere [19][20][21] (16) and P(36) ro-vibrational lines in the (2,0 0 ,1)←(0,0 0 ,0) vibrational combination band of the CO 2 molecule. The isotopic ratios were expressed in the typical δ 13 C ‰ and δ 18 1) and (2), respectively: ...
The 13C-urea breath test (13C-UBT), developed a few decades ago, is widely used as a non-invasive diagnostic method to detect only the presence of the gastric pathogen Helicobacter pylori infection; however, the actual disease state, i.e. whether the person harbouring H. pylori has peptic ulcer disease (PUD) or non-ulcerous dyspepsia (NUD), is still poorly understood. Nevertheless, the present 13C-UBT has numerous limitations, drawbacks and pitfalls owing to the ingestion of 13C-labelled external urea. Here, we show that H. pylori is able to utilize the natural 13C and 18O-urea inherently present in the gastric juice in humans for its urease activity which has never been explored before. In vitro measurements of isotopic fractionations of gastric juice urea provide new insights into the actual state of the infection of PUD or NUD. We also provide evidence of the unusual 13C and 18O-isotopic fractionations of breath CO2 that are distinctively altered in individuals with PUD encompassing both gastric and duodenal ulcers as well as with NUD by the enzymatic activity of H. pylori in the gastric niche without oral administration of any 13C-enriched external urea. This deepens our understanding of the UBT exploiting the natural 13C and 18O-gastric juice urea in the pathogenesis of H. pylori infection, reveals the actual disease state of PUD or NUD and thus offers novel opportunities for a simple, robust, cost-effective and non-toxic global strategy devoid of any 13C-enriched urea for treating these common diseases by a single breath test. Graphical AbstractUrea breath test without any external urea
... pylori negative, n = 31) based on the reports of both 'gold-standard' invasive and non-invasive tests i.e. endoscopy, biopsy-based rapid urease test (RUT) and 13 C-UBT. In 13 C-UBT, the value of δ DOB 13 C (‰) ⩾ 3‰ at 30 min was reflected as H. pylori positive [19,20]. The H. pylori infection status of all the enrolled subjects was confirmed only when both tests showed the same result. ...
The gastric pathogen Helicobacter pylori utilizes molecular hydrogen (H2) as a respiratory substrate during colonization in the gastric mucosa. However, the link between molecular H2 and the pathogenesis of peptic-ulcer disease (PUD) and non-ulcerous dyspepsia (NUD) by the enzymatic activity of H. pylori still remains mostly unknown. Here we provide evidence that breath H2 excretion profiles are distinctly altered by the enzymatic activity of H. pylori for individuals with NUD and PUD. We subsequently unravelled the potential molecular mechanisms responsible for the alteration of H2 in exhaled breath in association with peptic ulcers, encompassing both gastric and duodenal ulcers, along with NUD. We also established that carbon-isotopic fractionations in the acid-mediated bacterial environment regulated by bacterial urease activity cannot discriminate the actual disease state i.e. whether it is peptic ulcer or NUD. However, our findings illuminate the unusual molecular H2 in breath that can track the precise evolution of PUD and NUD, even after the eradication of H. pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing ¹³C-urea breath test (¹³C-UBT) fails to diagnose.
... A standard residual gas analyzer (RGA)-based mass spectrometry (MS) technique was employed to measure the masses of H 2 S (i.e. 34 amu) in breath samples [23,24]. The detailed measurement procedure by the RGA-MS system can be found in the supplementary material. ...
There is a pressing need to develop a novel early-detection strategy for the precise evolution of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) patients. The current method based on a hydrogen breath test (HBT) for the detection of SIBO is highly controversial. HBT has many limitations and drawbacks. It often fails to indentify SIBO when IBS individuals have 'non-hydrogen-producing' colonic bacteria. Here, we show that hydrogen sulphide (H2S) in exhaled breath is distinctly altered for diarrhea-predominant IBS individuals with positive and negative SIBO by the activity of intestinal sulphate-reducing bacteria. Subsequently, by analyzing the excretion kinetics of breath H2S, we found a missing link between breath H2S and SIBO when HBT often fails to diagnose SIBO. Moreover, breath H2S can track the precise evolution of SIBO, even after the eradication of bacterial overgrowth. Our findings suggest that the changes in H2S in the bacterial environment may contribute to the pathogenesis of SIBO and the breath H2S as a potential biomarker for non-invasive, rapid and precise assessment of SIBO without the endoscopy-based microbial culture of jejunal aspirates, and thus may open new perspectives into the pathophysiology of SIBO in IBS subjects.
... In recent years, different application protocols and detection devices were developed. A recently published study describes a residual gas analyser-based mass spectrometry approach with possible pointof-care application [39]. A further study has evaluated a low dose capsule-based UBT approach compared to conventional UBT and invasive tests [40]. ...
Since the first evidence demonstrating the dramatically high incidence of H. pylori infection and the subsequent medical challenges it incurs, health management of H. pylori infection has been a high priority for health authorities worldwide. Despite a decreasing rate of infection in western countries, prevalence of H. pylori infection in developing and in some industrial countries is still very high. Whereas treatment and vaccination against H. pylori is a contemporary issue in medical communities, selective treatment and prior high-throughput screening of the subject population is a major concern of health organizations. So far, diagnostic tests are either elaborative and require relatively advanced medical care infrastructure or they do not fulfill the criteria recommended by the Maastricht IV/Florence consensus report. In this review, in light of recent scientific studies, we highlight current and possible future approaches for the diagnosis of H. pylori. We point out that novel non-invasive tests may not only cover the requirements of gold standard methods in H. pylori detection but also offer the potential for risk stratification of infection in a high throughput manner.
... pylori positive patients: 124) and without the infection of H. pylori (H. pylori negative patients: 100) depending on the reports of gold standard invasive and non-invasive methods, i.e. endoscopy and biopsy based rapid urease test (RUT) and 13 C-urea breath test ( 13 C-UBT).The 13 C-UBT was considered to be indicative of H. pylori positive when δ DOB 13 C (‰) ≥ 3‰ [19][20][21] . There were no mismatches between the two test-reports of all the subjects enrolled in this study (Supplementary Table 1). ...
The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 ((18)O) and carbon-13 ((13)C)-isotopic fractionations of breath CO2 during glucose metabolism are poorly understood. Using the excretion dynamics of (18)O/(16)O and (13)C/(12)C-isotope ratios of breath CO2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of (18)O in breath CO2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of (18)O in breath CO2 were manifested in individuals without the infections. In contrast, the (13)C-isotopic enrichments of breath CO2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to (13)C-enriched glucose uptake, whereas a distinguishable change of breath (13)C/(12)C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the (18)O and (13)C-isotopic exchange in breath CO2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath (12)C(18)O(16)O and (13)C(16)O(16)O can be used as potential molecular biomarkers to distinctively track the pathogenesis of Helicobacter pylori and also for eradication purposes and thus may open new perspectives into the pathogen's physiology along with isotope-specific non-invasive diagnosis of the infection.
... It is therefore of immense interest to develop a simple, robust and cost-effective alternative noninvasive diagnostic tool for the 13 C-GBT that can reliably and accurately analyze breath samples in real-time at the pointof-care. We have recently developed and validated a simple, low-cost residual gas analyzer-mass spectrometry (RGA-MS) method for non-invasive diagnosis of H. pylori infection [10]. The aim of the present study was therefore to standardize and validate this novel analytical RGA-MS method in the 13 C-GBT for non-invasive assessment of pre-diabetes and type 2 diabetes mellitus in real time, and eventually to explore its true potential for routine clinical practice. ...
... We employed the residual gas analyzer-mass spectrometry (RGA-MS) that exploits a conventional quadrupole mass filter technology with a Faraday cup detector to measure the masses of 13 The RGA-MS system and its potential for measuring carbon isotopes with a typical precision of ±0.25‰ in breath samples has been described in detail in our previous study [10]. In brief, an RGA was coupled with a high vacuum chamber (~9.0 × 10 −8 Torr) and the baseline vacuum was achieved by two turbo-molecular pumps backed up with a diaphragm pump. ...
... The readout of this test, 15 N 2 , is detected using IRMS, and portable MS detection devices are available and under development 27 , supporting eventual development into a POC technology. Residual gas analyser MS, a technique with great potential for portability, has recently been shown to be effective in clinical IRMS 28 , and represents one avenue forward. As with any new potential diagnostic approach, ultimate clinical usage and utility must be determined in trials. ...
There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of (15)N2 in exhaled breath of infected rabbits within 5-10 min. No increase in (15)N2 is detected in uninfected animals, and the increases in (15)N2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.
