Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Functionalized N95 Face Mask with a Chemical-Free Paper-Based Collector for Exhaled Breath Analysis: SARS-CoV-2 Detection with a Printed Immunosensor as a Case Study.

Exhaled breath electrochemical sensing is a promising biomedical technology owing to its portability, painlessness, cost-effectiveness, and user-friendliness. Here, we present a novel approach for target analysis in exhaled breath by integrating a comfortable paper-based collector into an N95 face mask, providing a universal solution for analyzing several biomarkers. As a model analyte, we detected SARS-CoV-2 spike protein from the exhaled breath by sampling the target analyte into the collector, followed by its detection out of the N95 face mask using a magnetic bead-based electrochemical immunosensor. This approach was designed to avoid any contact between humans and the chemicals. To simulate human exhaled breath, untreated saliva samples were nebulized on the paper collector, revealing a detection limit of 1 ng/mL and a wide linear range of 3.7-10,000 ng/mL. Additionally, the developed immunosensor exhibited high selectivity toward the SARS-CoV-2 spike protein, compared to other airborne microorganisms, and the SARS-CoV-2 nucleocapsid protein. Accuracy assessments were conducted by analyzing the simulated breath samples spiked with varying concentrations of SARS-CoV-2 spike protein, resulting in satisfactory recovery values (ranging from 97 ± 4 to 118 ± 1%). Finally, the paper-based hybrid immunosensor was successfully applied for the detection of SARS-CoV-2 in real human exhaled breath samples. The position of the collector in the N95 mask was evaluated as well as the ability of this paper-based analytical tool to identify the positive patient.

Establishing Healthy Breath Baselines With Tin Oxide Sensors: Fundamental Building Blocks for Noninvasive Health Monitoring.

INTRODUCTION: Volatile organic compounds (VOCs) in breath serve as a source of biomarkers for medical conditions relevant to warfighter health including Corona Virus Disease and other potential biological threats. Electronic noses are integrated arrays of gas sensors that are cost-effective and miniaturized devices that rapidly respond to VOCs in exhaled breath. The current study seeks to qualify healthy breath baselines of exhaled VOC profiles through analysis using a commercialized array of metal oxide (MOX) sensors. MATERIALS AND METHODS: Subjects were recruited/consented through word of mouth and using posters. For each sample, breath was analyzed using an array of MOX sensors with parameters that were previously established. Data were also collected using a lifestyle questionnaire and from a blood test to assess markers of general health. Sensor data were processed using a feature extraction algorithm, which were analyzed through statistical approaches to identify correlations with confounding factors. Reproducibility was also assessed through relative standard deviation values of sensor features within a single subject and between different volunteers. RESULTS: A total of 164 breath samples were collected from different individuals, and 10 of these volunteers provided an additional 9 samples over 6 months for the longitudinal study. First, data from different subjects were analyzed, and the trends of the 17 extracted features were elucidated. This revealed not only a high degree of correlation between sensors within the array but also between some of the features extracted within a single sensor. This helped guide the removal of multicollinear features for multivariate statistical analyses. No correlations were identified between sensor features and confounding factors of interest (age, body mass index, smoking, and sex) after P-value adjustment, indicating that these variables have an insignificant impact on the observed sensor signal. Finally, the longitudinal replicates were analyzed, and reproducibility assessment showed that the variability between subjects was significantly higher than within replicates of a single volunteer (P-value = .002). Multivariate analyses within the longitudinal data displayed that subjects could not be distinguished from one another, indicating that there may be a universal healthy breath baseline that is not specific to particular individuals. CONCLUSIONS: The current study sought to qualify healthy baselines of VOCs in exhaled breath using a MOX sensor array that can be leveraged in the future to detect medical conditions relevant to warfighter health. For example, the results of the study will be useful, as the healthy breath VOC data from the sensor array can be cross-referenced in future studies aiming to use the device to distinguish disease states. Ultimately, the sensors may be integrated into a portable breathalyzer or current military gear to increase warfighter readiness through rapid and noninvasive health monitoring.

Diagnostic accuracy of an exhaled breath test for TB in hospitalized patients with cough or risk.

Closing the TB diagnostic gap is an urgent priority, for which non-sputum-based tests are needed. We evaluated the diagnostic accuracy of Aeonose, an exhaled breath test (EBT), as a TB triage test.Patients with cough or TB risk factors admitted to a tertiary hospital in Lima, Peru, were prospectively enrolled and underwent EBT. We evaluated EBT sensitivity and specificity for diagnosing pulmonary TB using culture and Xpert as primary and secondary reference standards and conducted stratified analyses based on risk factors.EBT sensitivity was 85% (95% CI 72.9-93.4), and specificity was 51% (95% CI 46.0-56.6) in the training cohort (n = 417). EBT sensitivity was 70% (95% CI 47.1-86.8), and specificity was 54% (95% CI 44.8-63.6) in the validation cohort (n = 139) using the culture reference standard, with higher sensitivity (78%) when using the Xpert reference standard (n = 156). Sensitivity (60%) and specificity (48%) were lower when patients with prior TB were included. In a subset of participants randomly selected for interviews, 94% (15/16) preferred EBT to sputum-based testing.EBT had moderate sensitivity and low specificity as a TB triage test in this hospitalised cohort with cough or risk factors. Diagnostic accuracy was lower in people with prior TB..

Studying drug excretion into exhaled breath aerosol - A workflow based on an impaction sampling device and LC-HRMS/MS analysis.

BACKGROUND: Exhaled breath (EB) aerosol was in principle shown to be a suitable matrix for bioanalysis of volatile but also non-volatile compounds. This attracted particular interest in the field of drug analysis. However, a big gap still exists in the understanding how and which drugs and/or their metabolites are excreted into exhaled breath and could thus actually be detected. The current study aimed to develop an analytical workflow for the qualitative detection of non-volatile drugs in EB aerosol microparticles. RESULTS: The analyte selection covered different drug classes such as antihypertensives, anticonvulsants or opioid analgesics to investigate and understand the excretion of drugs and their metabolites into EB aerosol. A device for collecting aerosol particles from the lung through impaction was used for the non-invasive sampling procedure. Three expiration cycles per participant and device were collected. The sample preparation consisted of a collector extraction with methanol. Qualitative method development and validation were performed using reversed-phase liquid chromatography (LC) coupled to orbitrap-based high-resolution mass spectrometry (HRMS). Qualitative method validation was done according to published recommendations and international guidelines. Parameters such as selectivity, carry-over, limits of detection and identification, recovery, matrix effects, and long-term stability were evaluated. The limits of detection ranged from 100 pg/collector to 10,000 pg/collector. The procedure was finally used to analyze a total of 31 patient EB samples and demonstrated that e.g., tilidine and its metabolite nortilidine as well as tramadol and its active metabolite O-desmethyltramadol can be detected in EB aerosol. SIGNIFICANCE AND NOVELTY: The work shows a comprehensive workflow for elucidating drug excretion into exhaled breath aerosol. This bioanalytical strategy and the corresponding novel data from this study are the foundation for further method development and to better understand, which drugs and their metabolites can be addressed by exhaled breath aerosol bioanalysis.

Pioneering noninvasive colorectal cancer detection with an AI-enhanced breath volatilomics platform.

Background: The sensitivity and specificity of current breath biomarkers are often inadequate for effective cancer screening, particularly in colorectal cancer (CRC). While a few exhaled biomarkers in CRC exhibit high specificity, they lack the requisite sensitivity for early-stage detection, thereby limiting improvements in patient survival rates. Methods: In this study, we developed an advanced Mass Spectrometry-based volatilomics platform, complemented by an enhanced breath sampler. The platform integrates artificial intelligence (AI)-assisted algorithms to detect multiple volatile organic compounds (VOCs) biomarkers in human breath. Subsequently, we applied this platform to analyze 364 clinical CRC and normal exhaled samples. Results: The diagnostic signatures, including 2-methyl, octane, and butyric acid, generated by the platform effectively discriminated CRC patients from normal controls with high sensitivity (89.7%), specificity (86.8%), and accuracy (AUC = 0.91). Furthermore, the metastatic signature correctly identified over 50% of metastatic patients who tested negative for carcinoembryonic antigen (CEA). Fecal validation indicated that elevated breath biomarkers correlated with an inflammatory response guided by Bacteroides fragilis in CRC. Conclusion: This study introduces a sophisticated AI-aided Mass Spectrometry-based platform capable of identifying novel and feasible breath biomarkers for early-stage CRC detection. The promising results position the platform as an efficient noninvasive screening test for clinical applications, offering potential advancements in early detection and improved survival rates for CRC patients.

Systematic study of polymer gas sampling bags for offline analysis of exhaled breath.

Polymeric bags are a widely applied, simple, and cost-effective method for the storage and offline analysis of gaseous samples. Various materials have been used as sampling bags, all known to contain impurities and differing in their cost, durability, and storage capabilities. Herein, we present a comparative study of several well-known bag materials, Tedlar (PVF), Kynar (PVDF), Teflon (PTFE), and Nalophan (PET), as well as a new material, ethylene vinyl copolymer (EVOH), commonly used for storing food. We investigated the influences of storage conditions, humidity, bag cleaning, and light exposure on volatile organic compound concentration (acetone, acetic acid, isoprene, benzene, limonene, among others) in samples of exhaled human breath stored in bags for up to 48 h. Specifically, we show high losses of short-chain fatty acids (SCFAs) in bags of all materials (for most SCFAs, less than 50% after 8 h of storage). We found that samples in Tedlar, Nalophan, and EVOH bags undergo changes in composition when exposed to UV radiation over a period of 48 h. We report high initial impurity levels in all the bags and their doubling after a period of 48 h. We compare secondary electrospray ionization and proton transfer reaction mass spectrometry in the context of offline analysis after storage in sampling bags. We provide an analytical perspective on the temporal evolution of bag contents by presenting the intensity changes of all significantm/zfeatures. We also present a simple, automated, and cost-effective offline sample introduction system, which enables controlled delivery of collected gaseous samples from polymeric bags into the mass spectrometer. Overall, our findings suggest that sampling bags exhibit high levels of impurities, are sensitive to several environmental factors (e.g. light exposure), and provide low recoveries for some classes of compounds, e.g. SCFAs.

Identification potential biomarkers for diagnosis, and progress of breast cancer by using high-pressure photon ionization time-of-flight mass spectrometry.

BACKGROUND: In this study, exhaled breath testing has been considered a promising method for the detection and monitoring of breast cancer (BC). METHODS: A high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform was used to detect volatile organic compounds (VOCs) in breath samples. Then, machine learning (ML) models were constructed on VOCs for the diagnosis of BC and its progression monitoring. Ultimately, 1981 women with useable breath samples were included in the study, of whom 937 (47.3 %) had been diagnosed with BC. VOC panels were used for ML model construction for BC detection and progression monitoring. RESULTS: On the blinded testing cohort, this VOC-based model successfully differentiated patients with and without BC with sensitivity, specificity, and area under receiver operator characteristic curve (AUC) values of 85.9 %, 90.4 %, and 0.946. The corresponding AUC values when differentiating between patients with and without lymph node metastasis (LNM) or between patients with tumor-node-metastasis (TNM) stage 0/I/II or III/IV disease were 0.840 and 0.708, respectively. While developed VOC-based models exhibited poor performance when attempting to differentiate between patients based on pathological patterns (Ductal carcinoma in situ (DCIS) vs Invasive BC (IBC)) or molecular subtypes (Luminal vs Human epidermal growth factor receptor 2 (HER2+) vs Triple-negative BC (TNBC)) of BC. CONCLUSION: Collectively, the HPPI-TOFMS-based breathomics approaches may offer value for the detection and progression monitoring of BC. Additional research is necessary to explore the fundamental mechanisms of the identified VOCs.

Yolk-Shell Hierarchical Pore Au@MOF Nanostructures: Efficient Gas Capture and Enrichment for Advanced Breath Analysis.

Surface-enhanced Raman scattering (SERS) offers a promising, cost-effective alternative for the rapid, sensitive, and quantitative analysis of potential biomarkers in exhaled gases, which is crucial for early disease diagnosis. However, a major challenge in SERS is the effective detection of gaseous analytes, primarily due to difficulties in enriching and capturing them within the substrate's "hotspot" regions. This study introduces an advanced gas sensor combining mesoporous gold (MesoAu) and metal-organic frameworks (MOFs), exhibiting high sensitivity and rapid detection capabilities. The MesoAu provides abundant active sites and interconnected mesopores, facilitating the diffusion of analytes for detection. A ZIF-8 shell enveloping MesoAu further enriches target molecules, significantly enhancing sensitivity. A proof-of-concept experiment demonstrated a detection limit of 0.32 ppb for gaseous benzaldehyde, indicating promising prospects for the rapid diagnosis of early stage lung cancer. This research also pioneers a novel approach for constructing hierarchical plasmonic nanostructures with immense potential in gas sensing.

Validity of rapid urease test using swab of gastric mucus to mucosal forceps and 13 C-urease breath test: a multicenter prospective observational study.

BACKGROUND: Theoretically, a rapid urease test (RUT) using a swab of the gastric wall (Swab-RUT) for Helicobacter pylori (H. pylori) is safe. However, the validity and utility of Swab-RUT remain unclear. Therefore, we assessed the validity and utility of Swab-RUT compared to RUT using mucosal forceps of the gastric wall (Forceps-RUT) and 13C-urea breath test (UBT). METHODS: This study was a multicenter prospective observational study. When the examinees were suspected of H. pylori infection during esophagogastroduodenoscopy, we performed Swab-RUT and Forceps-RUT continuously. When the examinees were not suspected of H. pylori infection, we performed Swab-RUT alone. We validated the status of H. pylori infection using UBT. RESULTS: Ninety-four examinees were enrolled from four institutions between May 2016 and December 2020 (median age [range], 56.5 [26-88] years). In this study, the sensitivity, specificity, and accuracy of Swab-RUT to UBT were 0.933 (95% confidence interval: 0.779-0.992), 0.922 (0.827-0.974), and 0.926 (0.853-0.970), respectively. The Kappa coefficient of Swab-RUT to UBT was 0.833, and that of Swab-RUT to forceps-RUT was 0.936. No complications were observed in this study. CONCLUSIONS: Swab-RUT is a valid examination for the status of H. pylori infection compared to the conventional Forceps-RUT.

Assessment of Biochemical, Inflammatory Biomarkers and Ultra-Processed Food Consumption in Children with Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study.

OBJECTIVE: This study evaluated anthropometric, biochemical, and inflammatory biomarkers, as well as dietary intake in Brazilian children diagnosed with small intestinal bacterial overgrowth (SIBO) and compared them with their counterparts without SIBO. METHODS: This was a cross-sectional study with 106 children aged 7 to 10 years. A glucose-hydrogen breath test was performed to diagnose small intestinal bacterial overgrowth (SIBO). Anthropometric and dietary characteristics were assessed. Blood samples were collected and serum biochemical parameters and cytokines were measured. RESULTS: The occurrence of SIBO was 13.2%. Age, BMI, BMI/age WC, BFP, sex and biochemical markers were similar between SIBO-positive and SIBO-negative children (p > 0.05). High consumption of ultra-processed foods tended to be higher in SIBO-positive compared to SIBO-negative children (47.8 ± 8.2 vs. 42.6 ± 9.5, p = 0.06). Serum levels of IL-17 were higher in SIBO-positive than in SIBO-negative children [69.5 (5.4-125.7) vs. 53.4 (2.3-157.7), p = 0.03], while serum levels of IL-10 were lower in SIBO-positive than in SIBO-negative children [2.3 (0.6-7.2) vs. 5.7 (0.5-30.8), p = 0.04]. Finally, in a logistic regression adjusted for sex, BMI and age, consumption of ultra-processed foods (p = 0.03) and IL-6 levels (p = 0.003) were found to contribute to the occurrence of SIBO. CONCLUSION: this study identified for the first time an occurrence of 13% of SIBO in children living in the northeastern region of Brazil and showed that consumption of ultra-processed foods and serum levels of IL-6 may influence the occurrence of the SIBO in the pediatrics population.

Volatile organic compounds in cancer and exhaled breath detection technology.

The detection of volatile organic compounds (VOCs) in breath has become a potential method for early cancer screening. Although this approach has attracted increasing attention from the both scientific and medical communities, it has not received appreciable traction in the clinical setting. There are two main obstacles. One involves the identification of specific biomarkers or combinations thereof especially in early cancer. The other is the lack the specialized equipment for breath analysis having the appropriate sensitivity and specificity. Using metabolomics, this chapter examines the research strategies involving gas biomarkers in cancer patient breath, cancer cell gas metabolites and synthetic biomarkers. We briefly explore gas biomarkers of seven cancers and introduce principles of detection and clinical application. Large analytical instruments and small sensor technology are highlighted. Challenges to VOC analysis are presented including clinical use, extraction and detection, miniaturization efforts and examination of metabolic VOC pathways. Finally, VOCs in cancer and in exhaled breath detection technology are summarized and future prospects explored.

A randomised controlled clinical study of standard triple therapy, bismuth-based quadruple therapy and sequential therapy for Helicobacter pylori infection in children.

BACKGROUND AND AIM: Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. METHODS: A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. RESULTS: In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. CONCLUSION: The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.

A cross-sectional study on metoprolol concentrations in various biological samples and their inter-correlations.

BACKGROUND: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. METHODS: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. RESULTS: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6-500, 0.4-500, and 0.7-10,000 µg·L- 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L- 1) and (0.60, 0.40, and 0.70 µg·L- 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3-4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L- 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. CONCLUSION: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments.

Stability of selected exhaled breath volatiles stored in Tenax®TA adsorbent tubes at -80 °C.

Preservation of the breath sample integrity during storage and transport is one of the biggest challenges in off-line exhaled breath gas analysis. In this context, adsorbent tubes are frequently used as storage containers for use with analytical methods employing gas chromatography with mass spectrometric detection. The key objective of this short communication is to provide data on the recovery of selected breath volatiles from Tenax®TA adsorbent tubes that were stored at -80 °C for up to 90 d. For this purpose, an Owlstone Medical's ReCIVA®Breath Sampler was used for exhaled breath collection. The following fifteen compounds, selected to cover a range of chemical properties, were monitored for their stability: isoprene, n-heptane, n-nonane, toluene, p-cymene, allyl methyl sulfide, 1-(methylthio)-propane, 1-(methylthio)-1-propene,α-pinene, DL-limonene,ß-pinene,γ-terpinene, 2-pentanone, acetoin and 2,3 butanedione. All compounds, but one (acetoin), were found to be stable during the first 4 weeks of storage (recovery within ± 2 × RSD). Furthermore, n-nonane was stable during the whole of the investigated period.

A stepwise surface ionization method for ion mobility spectrometry.

RATIONALE: The detection of organic nitrogen compounds in exhaled breath is expected to provide an early warning of diseases such as kidney disease. Detecting these trace disease markers in exhaled breath with complex composition and high moisture content is a challenge. Surface ionization (SI) shows a highly selective ionization of organic nitrogen compounds, and it is a good candidate for breath analysis combined with ion mobility spectrometry (IMS). METHODS: A stepwise SI method of low-temperature adsorption/high-temperature ionization was proposed, and trimethylamine (TMA) was detected when combined with an ion mobility spectrometer. TMA at different concentrations and humidity levels and spiked in human breath was detected to evaluate the method's properties. RESULTS: TMA with concentrations from 2 to 200 ppb was detected. The peak intensity of the TMA characteristic ions was linearly related to the "e" exponent of the concentration with a curve fit of 0.996. A standard deviation of less than 0.306% was obtained with 10 replicate analyses of 10 ppb TMA. The signal intensity difference between dry and wet (relative humidity > 93%) TMA samples is only 2.7%, and the recovery rate of the sample was 106.819%. CONCLUSIONS: SI-IMS based on the stepwise SI method has the advantages of low ionization temperature, high detection sensitivity, strong resistance to humidity interference, and good repeatability. It is a promising method for detecting organic nitrogen compounds in exhaled breath.

Extraction and characterization of exosomes from the exhaled breath condensate and sputum of lung cancer patients and vulnerable tobacco consumers-potential noninvasive diagnostic biomarker source.

Noninvasive sample sources of exosomes, such as exhaled breath and sputum, which are in close proximity to the tumor microenvironment and may contain biomarkers indicative of lung cancer, are far more permissive than invasive sample sources for biomarker screening. Standardized exosome extraction and characterization approaches for low-volume noninvasive samples are critically needed. We isolated and characterized exhaled breath condensate (EBC) and sputum exosomes from healthy nonsmokers (n= 30), tobacco smokers (n= 30), and lung cancer patients (n= 40) and correlated the findings with invasive sample sources. EBC samples were collected by using commercially available R-Tubes. To collect sputum samples the participants were directed to take deep breaths, hold their breath, and cough in a collection container. Dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy were used to evaluate the exosome morphology. Protein isolation, western blotting, exosome quantification via EXOCET, and Fourier transform infrared spectroscopy were performed for molecular characterization. Exosomes were successfully isolated from EBC and sputum samples, and their yields were adequate and sufficiently pure for subsequent downstream processing and characterization. The exosomes were confirmed based on their size, shape, and surface marker expression. Remarkably, cancer exosomes were the largest in size not only in the plasma subgroups, but also in the EBC (p < 0.05) and sputum (p= 0.0036) subgroups, according to our findings. A significant difference in exosome concentrations were observed between the control sub-groups (p < 0.05). Our research confirmed that exosomes can be extracted from noninvasive sources, such as EBC and sputum, to investigate lung cancer diagnostic biomarkers for research, clinical, and early detection in smokers.

The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review.

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.

Methane gas in breath test is associated with non-alcoholic fatty liver disease.

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.