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Identification of the breathing cycle forms the basis of any breath-by-breath gas exchange analysis. Classically, the breathing cycle is defined as the time interval between the beginning of two consecutive inspiration phases. Based on this definition, several research groups have developed algorithms designed to estimate the volume and rate of gas transferred across the alveolar membrane ("alveolar gas exchange"); however, most algorithms require measurement of lung volume at the beginning of the ith breath (VLi-1; i.e., the end-expiratory lung volume of the preceding ith breath). The main limitation of these algorithms is that direct measurement of VLi-1 is challenging and often unavailable. Two solutions avoid the requirement to measure VLi-1 by redefining the breathing cycle. One method defines the breathing cycle as the time between two equal fractional concentrations of lung expired oxygen (Fo2) (or carbon dioxide; Fco2), typically in the alveolar phase, whereas the other uses the time between equal values of the Fo2/Fn2 (or Fco2/Fn2) ratios [i.e., the ratio of fractional concentrations of lung expired O2 (or CO2) and nitrogen (N2)]. Thus, these methods identify the breathing cycle by analyzing the gas fraction traces rather than the gas flow signal. In this review, we define the traditional approach and two alternative definitions of the human breathing cycle and present the rationale for redefining this term. We also explore the strengths and limitations of the available approaches and provide implications for future studies.

Prolonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO2tox). PO2tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO2tox. Using a double-blind, randomized 'sham' controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 h. One test gas consisted of 100% O2(HBO) and the other was a gas mixture containing 30.6% O2with the balance N2(Nitrox). The high O2stress dive (HBO) and low O2stress dive (Nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO2tox and one subject terminated the dive early due to severe symptoms of PO2tox. No symptoms of PO2tox were reported following the nitrox dive. A partial least-squares discriminant analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (±2%) and sensitivity and specificity of 0.93 (±10%) and 0.94 (±10%), respectively. The resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.

Background: Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). Methods: We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. Results: Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. Conclusions: Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings. [ABSTRACT FROM AUTHOR]

Objective: To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province. Methods: A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18–75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT). Results: The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%–95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%–98.4%), 92.7% (38/41, 95%CI 84.4%–101.0%),88.4% (38/43，95%CI 78.4%–98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy. Conclusion: VPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. Methods: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. Results: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. Conclusions: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future. [ABSTRACT FROM AUTHOR]

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC. [ABSTRACT FROM AUTHOR]

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10−6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter. Author summary: Small intestine bacterial overgrowth (SIBO) is common in low- and middle-income country children with an incidence of up to 30% in some populations. SIBO has been documented as early as 18 weeks of age using the glucose-hydrogen breath test. SIBO is associated with future linear growth shortfalls and decreased language scores on neurodevelopmental testing. Other studies have linked SIBO to enteric inflammation but no work has directly examined histologic associations with the hydrogen breath test. Further, no work linking the duodenal adherent microbiota to breath testing has been published to date. We conducted glucose-hydrogen breath testing and duodenoscopy with biopsy on Bangladeshi toddlers. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. SIBO was associated with enterocyte injury and with a significant increase in Campylobacter species in biopsy samples. These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury. Further, they show a novel association between SIBO and Campylobacter species. [ABSTRACT FROM AUTHOR]

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms. [ABSTRACT FROM AUTHOR]

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA. [ABSTRACT FROM AUTHOR]

Background of the Study: Mammograms are sometimes met with issues of overdiagnosis and underdiagnosis; therefore, they are less reliable in identifying cancer in women with dense breasts. As a result, it is critical to be aware of other sensitive screening techniques for the early diagnosis of breast cancer. Aim: The ultimate objective of this study was to assess the knowledge of nursing undergraduates regarding non-invasive biomarkers, such as volatile organic compounds in breath, nipple aspirate fluid, sweat, urine, and tears, for the early detection of breast cancer to help improve patient care, determine the risk factors, and encourage practice of breast self-examination. Methods: Cross-sectional research was done in the Department of Nursing at Farasan campus using a self-structured questionnaire as the study tool. A total of 260 students willingly participated. The study tool had evaluation questions focused on the non-invasive biomarkers of breast cancer, risk factors, and breast self-examination practices to collect data. The data were subjected to descriptive and inferential statistics. The statistical significance was calculated at P <.05. Data analyses were done using Microsoft Excel (2013). Results: A s ignificant knowledge gap existed among the study participants about the non-invasive biomarkers of breast cancer. A lesser percentage of students (25%) stated that they do breast self-examination on a monthly basis. The most common reasons for not doing the breast self-examination were "not knowing how to do the breast self-examination" (77.3%), fear of a positive diagnosis (53.9%), thinking that they are not at risk as all were in their teens and hence not required (44.7%), and lack of time (48.7%). Age and frequency of breast self-examination were significantly associated (P <.05) as those few students (22.7%) who were doing breast self-examination practices every 2–4 months belonged to a higher study year. Furthermore, knowledge regarding incidence rates and health care expenditure by the government on breast cancer was also significantly low (P <.05). Conclusions: Outcomes would help prioritize actions to help future nurses better understand breast cancer, allowing them to extend patient care in the best way possible. [ABSTRACT FROM AUTHOR]

Background and Aim: To date, no randomized trials have compared the efficacy of 7‐day vonoprazan, amoxicillin, and metronidazole triple therapy (VAM) versus 7‐day vonoprazan, amoxicillin, and clarithromycin triple therapy (VAC) as a first‐line treatment for Helicobacter pylori eradication. This study was performed to compare the efficacy of VAM and VAC as first‐line treatments. Methods: This prospective multicenter randomized trial was performed in Japan and involved 124 H. pylori‐positive patients without a history of eradication. Patients without antibiotic resistance testing of H. pylori were eligible. The patients were randomized to receive either VAC (vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200 or 400 mg twice a day) or VAM (vonoprazan 20 mg + amoxicillin 750 mg + metronidazole 250 mg twice a day) for 7 days, with stratification by age and sex. Eradication success was evaluated using the 13C‐urea breath test. We evaluated safety using patient questionnaires (UMIN000025773). Results: The intention‐to‐treat and per‐protocol eradication rates of VAM were 91.3% (95% confidence interval [CI], 82.0–96.7%) and 92.6% (95% CI, 83.7–97.6%), respectively, and those of VAC were 89.1% (95% CI, 77.8–95.9%) and 96.1% (95% CI, 86.5–99.5%), respectively. No significant difference was observed between VAM and VAC in either analysis (P = 0.76 and P = 0.70, respectively). Abdominal fullness was more frequent in patients who received VAM than VAC. Conclusions: These findings suggest that VAM as a first‐line treatment in Japan can be categorized as grade B (intention‐to‐treat cure rate of 90–95%) and have potential as a first‐line national insurance ‐approved regimen. [ABSTRACT FROM AUTHOR]

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe. [ABSTRACT FROM AUTHOR]

BackgroundSeveral studies suggest that far-field transmission (>6 ft) explains a significant number of COVID-19 superspreading outbreaks.ObjectiveTherefore, quantifying the ratio of near- and far-field exposure to emissions from a source is key to better understanding human-to-human airborne infectious disease transmission and associated risks.MethodsIn this study, we used an environmentally-controlled chamber to measure volatile organic compounds (VOCs) released from a healthy participant who consumed breath mints, which contained unique tracer compounds. Tracer measurements were made at 0.76 m (2.5 ft), 1.52 m (5 ft), 2.28 m (7.5 ft) from the participant, as well as in the exhaust plenum of the chamber.ResultsWe observed that 0.76 m (2.5 ft) trials had ~36-44% higher concentrations than other distances during the first 20 minutes of experiments, highlighting the importance of the near-field exposure relative to the far-field before virus-laden respiratory aerosol plumes are continuously mixed into the far-field. However, for the conditions studied, the concentrations of human-sourced tracers after 20 minutes and approaching the end of the 60-minute trials at 0.76 m, 1.52 m, and 2.28 m were only ~18%, ~11%, and ~7.5% higher than volume-averaged concentrations, respectively.SignificanceThis study suggests that for rooms with similar airflow parameters disease transmission risk is dominated by near-field exposures for shorter event durations (e.g., initial 20-25-minutes of event) whereas far-field exposures are critical throughout the entire event and are increasingly more important for longer event durations.Impact statementWe offer a novel methodology for studying the fate and transport of airborne bioaerosols in indoor spaces using VOCs as unique proxies for bioaerosols. We provide evidence that real-time measurement of VOCs can be applied in settings with human subjects to estimate the concentration of bioaerosol at different distances from the emitter. We also improve upon the conventional assumption that a well-mixed room exhibits instantaneous and perfect mixing by addressing spatial distances and mixing over time. We quantitatively assessed the exposure levels to breath tracers at alternate distances and provided more insights into the changes on "near-field to far-field" ratios over time. This method can be used in future to estimate the benefits of alternate environmental conditions and occupant behaviors.

Helicobacter pylori (H. pylori) infection is a cause of gastric disorders and is treated mainly by pharmacotherapy with antimicrobial agents. An association has been reported between dental caries and H. pylori infection. As antimicrobial agents are less effective inside dental caries because of impaired blood circulation, the presence of untreated dental caries (decayed teeth) may influence the success of H. pylori eradication treatment. In this cross-sectional study, we examined whether failed eradication of H. pylori was associated with decayed teeth in Japanese adults. Enrolled were 226 participants who received dental checkups among those treated for eradication of H. pylori at Asahi University Hospital between April 2019 and March 2021. Treatment efficacy was assessed by urea breath test. Eradication failed in 38 participants (17%), decayed teeth in 32 participants (14%), and number of 0.34 teeth per participants. Multivariate logistic regression analyses showed that failed eradication of H. pylori was associated with decayed teeth (presence: odds ratio, 2.672; 95% confidence interval, 1.093–6.531) after adjusting for gender, age, and brushing frequency. These results indicate that failed eradication of H. pylori was associated with decayed teeth and suggest that untreated dental caries may impact treatment for eradication of H. pylori. [ABSTRACT FROM AUTHOR]

Background: Breath testing using an electronic nose has been recognized as a promising new technique for the early detection of lung cancer. Imbalanced data are commonly observed in electronic nose studies, but methods to address them are rarely reported. Objective: The objectives of this study were to assess the accuracy of electronic nose screening for lung cancer with imbalanced learning and to select the best mechanical learning algorithm. Methods: We conducted a case‒control study that included patients with lung cancer and healthy controls and analyzed metabolites in exhaled breath using a carbon nanotube sensor array. The study used five machine learning algorithms to build predictive models and a synthetic minority oversampling technique to address imbalanced data. The diagnostic accuracy of lung cancer was assessed using pathology reports as the gold standard. Results: We enrolled 190 subjects between 2020 and 2023. A total of 155 subjects were used in the final analysis, which included 111 lung cancer patients and 44 healthy controls. We randomly divided samples into one training set, one internal validation set, and one external validation set. In the external validation set, the summary sensitivity was 0.88 (95% CI 0.84–0.91), the summary specificity was 1.00 (95% CI 0.85–1.00), the AUC was 0.96 (95% CI 0.94–0.98), the pAUC was 0.92 (95% CI 0.89–0.96), and the DOR was 207.62 (95% CI 24.62–924.64). Conclusion: Electronic nose screening for lung cancer is highly accurate. The support vector machine algorithm is more suitable for analyzing chemical sensor data from electronic noses. [ABSTRACT FROM AUTHOR]

Historical events leading to the development of the first handheld instrument for breath alcohol analysis using an electrochemical sensor are reviewed. The first prototype instrument, known as the Alcolmeter Pocket Model, became available in 1972 and weighed only 180 g and was about the size of a cellphone. By the mid-1970s, the Alcolmeter instrument was used by police forces in several countries as a preliminary roadside test of driver sobriety. Positive results in a roadside breath test were considered sufficient evidence to arrest a suspect for further evaluation and testing. This might entail an evidential-quality breath alcohol test or taking a sample of the driver's blood for analysis at a forensic laboratory. The main advantages of breath testing over blood testing are the non-invasive nature of the sampling procedure compared with sticking a needle in a vein to draw blood, and obtaining immediate information whether or not a person is in breach of the drunk driving legislation. [ABSTRACT FROM AUTHOR]

Background/Aims We performed a systematic review and meta-analysis evaluating the symptomatic response rate to antibiotics in patients with small intestinal bacterial overgrowth (SIBO). Similarly, we performed a meta-analysis on the symptomatic response to antibiotics in irritable bowel syndrome (IBS) patients with and without SIBO. Methods MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched from inception to March 2021. Randomized controlled trials and prospective studies reporting dichotomous outcomes were included. Results There were 6 studies included in the first meta-analysis comparing the efficacy of antibiotics to placebo or no antibiotic. This included 196 patients, of whom 101 received antibiotics and 95 received placebo or no antibiotics. Significantly more patients improved with antibiotics (relative risk [95% CI] = 2.46 [1.33-4.55], P = 0.004). There were 4 studies included in the analysis comparing symptomatic response rates in IBS patients with or without SIBO with 266 IBS patients, of whom 172 had SIBO and 94 did not. The pooled response rate for symptomatic response was 51.2% in the SIBO group vs 23.4% in the no SIBO group, respectively. Significantly more IBS patients with SIBO responded to antibiotics compared to those without SIBO (relative risk [95% CI] = 2.07 [1.40-3.08], P = 0.0003). Conclusions Antibiotics appear to be efficacious in treating SIBO, although small sample sizes and poor data quality limit this interpretation. Symptomatic response rates also appear to be higher in IBS patients with SIBO. This may be the first example of precision medicine in IBS as opposed to our current empiric treatment approach. Large-multicenter studies are needed to verify the results. [ABSTRACT FROM AUTHOR]

Alcohol ingested by humans can be analyzed via breath tests; however, approximately 1% can be excreted via the skin. In this paper, we present a capacitive sensor using hydrophobically treated anodic aluminum oxide (AAO) capable of detecting alcohol excreted through the epidermis. The degree of hydrophobicity based on the duration of exposure to 3-aminopropyltriethoxysilane vapor comprising a small number of Si–NH2 functional groups on the AAO surface was confirmed and the optimal exposure time was confirmed to be 60 min. The hydrophobized AAO showed a 4.8% reduction in sensitivity to moisture. Simultaneously, the sensitivity of the sensor to ethanol decreased by only 12%. Lastly, the fabricated sensor was successfully operated by attaching it to an ankle-type breathalyzer. [ABSTRACT FROM AUTHOR]

Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal symptoms (Rome IV) in postmenopausal women with functional constipation (FC, n = 40) as compared with age-adjusted postmenopausal women without FC. All women controlled their TRP intake in their daily diet. Urinary levels of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (indican, 3-IS), were determined by liquid chromatography/tandem mass spectrometry. Dysbiosis was assessed by a hydrogen–methane breath test. Women with FC consumed less TRP and had a lower urinary level of 5-HIAA, but higher levels of KYN and 3-IS compared with controls. The severity of symptoms showed a negative correlation with the 5-HIAA level, and a positive correlation with the 3-IS level. In conclusion, changes in TRP metabolism may contribute to FC in postmenopausal women, and dysbiosis may underlie this contribution. [ABSTRACT FROM AUTHOR]

Objective: To confirm the relevance of upper and lower airway inflammation in eosinophilic chronic rhinosinusitis (ECRS), the effects of endoscopic sinus surgery (ESS) on lower airway functions and inflammation need to be examined in ECRS patients. Methods: Chronic rhinosinusitis patients with nasal polyps (25 non-ECRS, 28 ECRS) were enrolled. The 12 patients in the ECRS group had comorbid asthma, in contrast to none in the non-ECRS group. We divided ECRS patients into 2 groups of ECRS with and without asthma. Clinical markers, including fraction of exhaled nitric oxide (FeNO), respiratory functions, and the Asthma Control Test (ACT) questionnaire, were investigated before and after ESS. Results: The FeNO levels in the ECRS with asthma group decreased after ESS. The mean FeNO levels in this group were 56.3 ppb before ESS and 24.9, 25.1, 25.0, and 15.5 ppb 1, 2, 3, and 4 months, respectively, after ESS. The mean forced expiratory rates in 1 second before and after ESS were 67.6% and 73.0%, respectively. The mean maximal expiratory flow rates at 50% of the vital capacity before and after ESS were 45.8% and 58.0%, respectively. Significant differences were observed in respiratory functions before and after ESS. The mean ACT scores in the ECRS with asthma group before and after ESS were 17.5 and 23.5, respectively. The ACT scores were significantly higher after than before ESS. Conclusions: The present results indicate that ECRS and bronchial asthma are common eosinophilic airway inflammatory diseases, and ESS for eosinophilic sinusitis may improve lower airway function. [ABSTRACT FROM AUTHOR]

In recent times, the global landscape of disease detection and monitoring has been profoundly influenced by the convergence of nanotechnology and biosensing techniques. Biosensors have enormous potential to monitor human health, with flexible or wearable variants, through monitoring of biomarkers in clinical and biological behaviors and applications related to health and disease, with increasing biorecognition, sensitivity, selectivity, and accuracy. The emergence of nanomaterial-based biosensors has ushered in a new era of rapid and sensitive diagnostic tools, offering unparalleled capabilities in the realm of disease identification. Even after the declaration of the end of the COVID-19 pandemic, the demand for efficient and accessible diagnostic methodologies has grown exponentially. In response, the integration of nanomaterial biosensors into breathalyzer devices has gained considerable attention as a promising avenue for low-cost, non-invasive, and early detection of COVID-19. This review delves into the forefront of scientific advancements, exploring the potential of emerging nanomaterial biosensors within breathalyzers to revolutionize the landscape of COVID-19 detection, providing a comprehensive overview of their principles, applications, and implications. [ABSTRACT FROM AUTHOR]

Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments. Current methods to monitor ketones include urine dipsticks, capillary blood monitors, and breath analyzers. However, these existing methods have certain disadvantages that preclude them from being used more widely. In this work, we introduce a novel acetone sensor device that can detect acetone levels in breath and overcome the drawbacks of existing sensing approaches. The critical element of the device is a robust sensor with the capability to measure acetone using a complementary metal oxide semiconductor (CMOS) chip and convenient data analysis from a red, green, and blue deconvolution imaging approach. The acetone sensor device demonstrated sensitivity of detection in the micromolar-concentration range, selectivity for detection of acetone in breath, and a lifetime stability of at least one month. The sensor device utility was probed with real tests on breath samples using an established blood ketone reference method. [ABSTRACT FROM AUTHOR]

Objective: To compare the Rapid Shallow Breathing Index (RSBI) obtained by the ventilometer and from mechanical ventilation parameters. Methods: Randomized crossover trial, including 33 intubated patients, on mechanical ventilation for at least 24 hours, undergoing spontaneous breathing test. Patients were submitted to the measurement of RSBI by four methods: disconnected from the ventilator through the ventilometer; in Pressure Support Ventilation (PSV) mode at a pressure of 7.ßcm H2O; in Continuous Positive Airway Pressure (CPAP) mode at a pressure of 5.ßcmH2O with flow trigger; in CPAP mode at a pressure of 5.ßcmH2O with pressure trigger. Results: No significant difference was detected between the RSBI obtained by the ventilometer and in the CPAP mode with flow and pressure triggers, however, in the PSV mode, the values were lower than in the other measurements (p.ß

Exhaled breath vapor contains hundreds of volatile organic compounds (VOCs), which are the byproducts of health and disease metabolism, and they have clinical and diagnostic potential. Simultaneous collection of breath VOCs and background environmental VOCs is important to ensure analyses eliminate exogenous compounds from clinical studies. We present a mobile sampling system to extract gaseous VOCs onto commercially available sorbent-packed thermal desorption tubes. The sampler can be connected to a number of commonly available disposable and reusable sampling bags, in the case of this study, a Tedlar bag containing a breath sample. Alternatively, the inlet can be left open to directly sample room or environmental air when obtaining a background VOC sample. The system contains a screen for the operator to input a desired sample volume. A needle valve allows the operator to control the sample flow rate, which operates with an accuracy of -1.52 ± 0.63% of the desired rate, and consistently generated that rate with 0.12 ± 0.06% error across repeated measures. A flow pump, flow sensor and microcontroller allow volumetric sampling, as opposed to timed sampling, with 0.06 ± 0.06% accuracy in the volume extracted. Four samplers were compared by sampling a standard chemical mixture, which resulted in 6.4 ± 4.7% error across all four replicate modular samplers to extract a given VOC. The samplers were deployed in a clinical setting to collect breath and background/environmental samples, including patients with active SARS-CoV-2 infections, and the device could easily move between rooms and can undergo required disinfection protocols to prevent transmission of pathogens on the case exterior. All components required for assembly are detailed and are made publicly available for non-commercial use, including the microcontroller software. We demonstrate the device collects volatile compounds, including use of chemical standards, and background and breath samples in real use conditions.

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration however require other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points, oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC–MS-MS. At the second time point, 98% of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100% in oral fluid, 98% in exhaled breath). Methadone-related results were 100% positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6%). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices. [ABSTRACT FROM AUTHOR]

Ventilator associated pneumonia (VAP) is an infectious disease in clinic with high incidence rate (about 5%-40%) and mortality (about 10%), which is mainly caused by bacteria. At present, the clinical diagnosis of VAP depends on the microbial pathogen diagnosis of sputum samples from the lower respiratory tract. The whole process takes more than 24 hours, which is easy to cause antibiotic misuse and initial treatment failure. In recent years, breath test has received widespread attention due to its non-invasive and convenient characteristics, which attempt to screen and diagnose VAP through analysis of volatile organic compounds (VOCs) in exhalation. Therefore, the research on characterization of VOCs released by VAP pathogens has certain guiding significance for the related breath tests. In this study, the main VAP pathogenic bacteria, including P. aeruginosa, S. aureus, E. coli, E. cloacae, K. pneumoniae, A. baumannii, S. maltophilia, and S. epidermidis, were cultured in tryptic soy broth (TSB) culture medium in vitro, and their headspace samples were obtained after 10 hours of shaking culture. Then, non-targeted detection of VOCs in the headspace was performed by using solid phase microextraction coupled to gas chromatography-mass spectrometry (SPME-GC-MS). It was found that a total of 44 differential amounts of VOCs were released by the 8 strains. Subsequently, these bacterial VOCs were classified and discussed according to ketones, aldehydes, ethers, alcohols, acids, esters, alkanes, benzenes, amides, and (nitrogen-containing) heterocycles. These results showed that there was some consistency in the types of VOCs released by the 8 VAP pathogens, such as the production of dimethyl ether and methyl mercaptan. However, there were some differences in the released VOCs among the different pathogens. For example, only S. aureus released 2-butanone and 3-hydroxy-2-butanone, only E. coli produced acetic acid, only E. coli, S. maltophilia, and S. aureus produced N-nenenebc methylformamide. In addition, K. pneumoniae and P. aeruginosa released dimethyl disulfide (DMDS), and S. maltophilia released dimethyl trisulfide (DMTS). This study systematically reports the similarities and differences in the types of VOCs released by VAP pathogens, providing a reference and foundament for VAP related breath research. In the future, it is expected to achieve rapid and non-invasive screening of VAP through exhalation. However, this study did not detect clinically isolated strains or samples, and it was not possible to verify whether there were any differences in results between standard strains and clinical strains. In future work, it is necessary to consider the characteristic spectra of clinically isolated strains and the landmark VOCs in the exhalation of clinical patients. [ABSTRACT FROM AUTHOR]

Background/Aims An increase in postprandial intestinal gas plays a role in bloating symptoms. We aim to study the utility of spot breath hydrogen (H2) level in predicting the response to a low fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) diet. Methods Patients with functional gastrointestinal disorders diagnosed by Rome IV criteria with bothersome bloating for > 6 months were prospectively enrolled. Patients completed 7-day food diaries and collected a breath sample 2 hours after their usual lunch at baseline and 4 weeks after low FODMAPs dietary advice by a dietitian. The responder was defined as an improvement of ≥ 30% bloating scores in the fourth week. Results Thirty-eight patients (32 female, 52.6 ± 13.8 years; 22 irritable bowel syndrome) completed the study. Twenty-one patients (55%) were classified as responders. Baseline global gastrointestinal symptoms, bloating, abdominal pain scores, and numbers of high FODMAPs items were similar between responders and non-responders. Both groups significantly decreased high FODMAPs items intake with similar numbers at the follow-up. The area under the curve for predicting low FODMAPs responsiveness using baseline H2 levels was 0.692 (95%CI, 0.51-0.86; P < 0.05), with the best cutoff at 8 parts per million (sensitivity 66.7%, specificity 82.4%). 66% of responders had baseline H2 level > 8 parts per million vs 17% of non-responders ( P < 0.05). The baseline spot hydrogen level in responders was 9.5 (3.3-17.3) vs 4.5 (3.3-6.3) in non-responders ( P < 0.05). Conclusions A higher baseline breath hydrogen level was associated with bloating improvement after low FODMAPs dietary advice. A spot breath test after lunch, a simple point-of-care test, is possibly helpful in managing patients with bloating. [ABSTRACT FROM AUTHOR]

Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21–32 and seven males, age: 21–55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007–0.030 g/210 L) or ten puffs (013–0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results. [ABSTRACT FROM AUTHOR]

Simple Summary: The current diagnostic modalities used during colorectal cancer follow-up appointments are known to have a limited sensitivity to detect recurrent disease. An electronic nose to detect volatile organic compounds (VOCs) in breath is shown to be a promising novel tool in the primary detection of lung cancer and colorectal cancer. To explore the potential role of an electronic nose in follow-up appointments for colorectal cancer patients, we evaluated the effects of surgery with curative intent on the exhaled VOC pattern. This pilot study showed that the VOC pattern changed shortly after surgery, paving the way for use in further clinical trials to address its added value during CRC follow-up appointments, and its ability to detect recurrent disease. As current follow-up modalities for colorectal carcinoma (CRC) have restricted sensitivity, novel diagnostic tools are needed. The presence of CRC changes the endogenous metabolism, resulting in the release of a specific volatile organic compounds (VOC) pattern that can be detected with an electronic nose or AeonoseTM. To evaluate the use of an electronic nose in the follow-up of CRC, we studied the effect of curative surgery on the VOC pattern recognition using AeonoseTM. A prospective cohort study was performed, in which 47 patients diagnosed with CRC were included, all of whom underwent curative surgical resection. Breath testing was performed before and after surgery using the AeonoseTM. A machine learning model was developed by discerning between the 94 pre-and postoperative breath samples. The training model differentiated between the pre-and postoperative CRC breath samples with a sensitivity and specificity of 0.78 (95%CI 0.61–0.90) and 0.73 (95%CI 0.56–0.86), respectively, with an accuracy of 0.76 (95%CI 0.66–0.85), and an area under the curve of 0.79 (95%CI 0.68–0.89). The internal validation of the test set resulted in an accuracy of 0.75 (95%CI 0.51–0.91) and AUC of 0.82 (95%CI 0.61–1). In conclusion, our results suggest that the VOC pattern of CRC patients is altered by curative surgery in a short period, indicating that the exhaled VOCs might be closely related to the presence of CRC. However, to use AeonoseTM as a potential diagnostic tool in the clinical follow-up of CRC patients, the performance of the models needs to be improved through further large-scale prospective research. [ABSTRACT FROM AUTHOR]

The interest around analysis of volatile organic compounds (VOCs) within breath has increased in the last two decades. Uncertainty remains around standardisation of sampling and whether VOCs within room air can influence breath VOC profiles. To assess the abundance of VOCs within room air in common breath sampling locations within a hospital setting and whether this influences the composition of breath. A secondary objective is to investigate diurnal variation in room air VOCs. Room air was collected using a sampling pump and thermal desorption (TD) tubes in the morning and afternoon from five locations. Breath samples were collected in the morning only. TD tubes were analysed using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS). A total of 113 VOCs were identified from the collected samples. Multivariate analysis demonstrated clear separation between breath and room air. Room air composition changed throughout the day and different locations were characterized by specific VOCs, which were not influencing breath profiles. Breath did not demonstrate separation based on location, suggesting that sampling can be performed across different locations without affecting results.

Background: Until now, there have been no randomized controlled trials directly evaluating the efficacy of high-dose ilaprazole-amoxicillin dual therapy (HT) in comparison to other standard treatments for H. pylori (Helicobacter pylori) infection. This study aimed to compare the effectiveness and safety of HT with bismuth quadruple therapy (BQT) as an initial treatment for H. pylori. Methods: This single-center, prospective, randomized clinical controlled trial recruited 225 consecutive patients. They were assigned to either HT group (ilaprazole, 10 mg, twice daily; amoxicillin 1,000 mg, three times daily) or BQT group (compound bismuth aluminate granules, 2.6 g, three times daily; ilaprazole, 5 mg, twice daily; amoxicillin, 1,000 mg, twice daily; clarithromycin, 500 mg, twice daily) for 14 days. The 13C-urea breath test assessed eradication success 4 weeks after treatment. The primary outcome focused on the eradication rate, with secondary outcomes including safety and compliance. Results: From February 2023 to March 2023, 228 subjects were screened, and 225 were randomized. The HT and BQT groups showed eradication rates of 76.3% and 61.3% (p = 0.015) both by intention-to-treat (ITT) analysis and per-protocol (PP) analysis. HT was associated with fewer adverse events than BQT (27.2% vs. 81.8%, p = 0.002). The most commonly reported adverse events was bitter taste of mouth (3.5% vs. 60.4%, p < 0.001). There was no significant difference in compliance between the two groups (89.5% vs. 92.8%, p = 0.264). Conclusion: The 14-day HT treatment demonstrates better efficacy in H. pylori eradication treatment and improved safety and compliance compared to BQT. The results provide supporting evidence for 14-day HT can be potentially considered as a first-line regimen for empirical treatment. [ABSTRACT FROM AUTHOR]

Background: Cirrhosis detection in primary care relies on low-performing biomarkers. Consequently, up to 75% of subjects with cirrhosis receive their first diagnosis with decompensation when causal treatments are less effective at preserving liver function. We investigated an unprecedented approach to cirrhosis detection based on dynamic breath testing. Methods: We enrolled 29 subjects with cirrhosis (Child–Pugh A and B), and 29 controls. All subjects fasted overnight. Breath samples were taken using Breath Biopsy® before and at different time points after the administration of 100 mg limonene. Absolute limonene breath levels were measured using gas chromatography–mass spectrometry. Results: All subjects showed a >100-fold limonene spike in breath after administration compared to baseline. Limonene breath kinetics showed first-order decay in >90% of the participants, with higher bioavailability in the cirrhosis group. At the Youden index, baseline limonene levels showed classification performance with an area under the roc curve (AUROC) of 0.83 ± 0.012, sensitivity of 0.66 ± 0.09, and specificity of 0.83 ± 0.07. The best performing timepoint post-administration was 60 min, with an AUROC of 0.91, sensitivity of 0.83 ± 0.07, and specificity of 0.9 ± 0.06. In the cirrhosis group, limonene bioavailability showed a correlation with MELD and fibrosis indicators, and was associated with signs of portal hypertension. Conclusions: Dynamic limonene breath testing enhances diagnostic performance for cirrhosis compared to static testing. The correlation with disease severity suggests potential for monitoring therapeutic interventions. Given the non-invasive nature of breath collection, a dynamic limonene breath test could be implemented in primary care. [ABSTRACT FROM AUTHOR]

Exhaled breath analysis has attracted considerable attention as a noninvasive and portable health diagnosis method due to numerous advantages, such as convenience, safety, simplicity, and avoidance of discomfort. Based on many studies, exhaled breath analysis is a promising medical detection technology capable of diagnosing different diseases by analyzing the concentration, type and other characteristics of specific gases. In the existing gas analysis technology, the electronic nose (eNose) analysis method has great advantages of high sensitivity, rapid response, real-time monitoring, ease of use and portability. Herein, this review is intended to provide an overview of the application of human exhaled breath components in disease diagnosis, existing breath testing technologies and the development and research status of electronic nose technology. In the electronic nose technology section, the three aspects of sensors, algorithms and existing systems are summarized in detail. Moreover, the related challenges and limitations involved in the abovementioned technologies are also discussed. Finally, the conclusion and perspective of eNose technology are presented. [ABSTRACT FROM AUTHOR]

Exhaled breath condensate (EBC) is routinely collected and analyzed in breath research. Because it contains aerosol droplets, EBC samples from SARS-CoV-2 infected individuals harbor the virus and pose the threat of infectious exposure. We report for the first time a safe and consistent method to fully inactivate SARS-CoV-2 in EBC samples and make EBC samples safe for processing and analysis. EBC samples containing infectious SARS-CoV-2 were treated with several concentrations of acetonitrile. The most commonly used 10% acetonitrile treatment for EBC processing failed to completely inactivate the virus in samples and viable virus was detected by the assay of SARS-CoV-2 infection of Vero E6 cells in a biosafety level 3 laboratory. Treatment with either 50% or 90% acetonitrile was effective to completely inactivate the virus, resulting in safe, non-infectious EBC samples that can be used for metabolomic analysis. Our study provides SARS-CoV-2 inactivation protocol for the collection and processing of EBC samples in the clinical setting and for advancing to metabolic assessments in health and disease.

Due to COVID-19 travel disruptions, the International Association of Breath Research hosted the planned 2021 Breath Summit virtually as a symposium with oral and poster presentations. The event was comprised of a week-long social media asynchronous online event for sharing research abstracts, posters and discussions. Subsequently, there were two days of real-time webinar platform interactions each featuring three technical presentations, open forum questions, answers, and commentary. The symposium was well attended and well received. It allowed the breath community to share new research and to reconnect with colleagues and friends. This report presents an overview of the topics presented and various salient discussion points.

Respiratory viral infections are considered a major public health threat, and breath metabolomics can provide new ways to detect and understand how specific viruses affect the human pulmonary system. In this pilot study, we characterized the metabolic composition of human breath for an early diagnosis and differentiation of influenza viral infection, as well as other types of upper respiratory viral infections. We first studied the non-specific effects of planned seasonal influenza vaccines on breath metabolites in healthy subjects after receiving the immunization. We then investigated changes in breath content from hospitalized patients with flu-like symptoms and confirmed upper respiratory viral infection. The exhaled breath was sampled using a custom-made breath condenser, and exhaled breath condensate (EBC) samples were analysed using liquid chromatography coupled to quadruplole-time-of-flight mass spectrometer (LC-qTOF). All metabolomic data was analysed using both targeted and untargeted approaches to detect specific known biomarkers from inflammatory and oxidative stress biomarkers, as well as new molecules associated with specific infections. We were able to find clear differences between breath samples collected before and after flu vaccine administration, together with potential biomarkers that are related to inflammatory processes and oxidative stress. Moreover, we were also able to discriminate samples from patients with flu-related symptoms that were diagnosed with confirmatory respiratory viral panels (RVPs). RVP positive and negative differences were identified, as well as differences between specific viruses defined. These results provide very promising information for the further study of the effect of influenza A and other viruses in human systems by using a simple and non-invasive specimen like breath.

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.

BackgroundAlcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol.MethodsWe computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in 49 studies.ResultsMeta-regression analyses indicated a significant and positive effect of pre-study drinks per month on alcohol-induced stimulation (β = 0.142, p

BackgroundA low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session.MethodsData were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7 ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway.ResultsContrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures.ConclusionThese data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Gastroparesis (GP) is a chronic disease characterized by upper gastrointestinal symptoms, primarily nausea and vomiting, and delayed gastric emptying (GE), in the absence of mechanical GI obstruction. The underlying pathophysiology of GP remains unclear, but factors contributing to the condition include vagal nerve dysfunction, impaired gastric fundic accommodation, antral hypomotility, gastric dysrhythmias, and pyloric dysfunction. Currently, gastric emptying scintigraphy (GES) is considered the gold standard for GP diagnosis. However, the overall delay in GE weakly correlates with GP symptoms and their severity. Recent research efforts have focused on developing treatments that address the presumed underlying pathophysiological mechanisms of GP, such as pyloric hypertonicity, with Gastric Peroral Endoscopic Myotomy (G-POEM) one of these procedures. New promising diagnostic tools for gastroparesis include wireless motility capsule (WMC), the 13 carbon-GE breath test, high-resolution electrogastrography, and the Endoluminal Functional Lumen Imaging Probe (EndoFLIP). Some of these tools assess alterations beyond GE, such as muscular electrical activity and pyloric tone. These modalities have the potential to characterize the pathophysiology of gastroparesis, identifying patients who may benefit from targeted therapies. The aim of this review is to provide an overview of the current knowledge on diagnostic pathways in GP, with a focus on the association between diagnosis, symptoms, and treatment. [ABSTRACT FROM AUTHOR]

Background: The day-to-day (DTD) management model encourages patients to actively participate in their healthcare by setting goals. We determined the effectiveness of the DTD model in the treatment of Helicobacter pylori (H. pylori) infection, as compared with conventional outpatient education (OE). Methods: We randomized 254 H. pylori-positive patients into a DTD group (127 patients) and an OE group (127 patients) prior to primary treatment with 14-day bismuth-containing quadruple therapy, including esomeprazole, amoxicillin, and clarithromycin. Both groups received consistent medication instructions. Patients in the DTD group recorded daily attendance after completing their daily medication plan from day 1 to day 14. The medication compliance, follow-up compliance, H. pylori eradication rates, and adverse events (AEs) were evaluated. Results: In the modified intention-to-treat (MITT) and per-protocol (PP) analyses, the DTD group showed significantly higher medication compliance than the OE group (P = 0.001 and P = 0.031, respectively). Both the MITT and PP analyses showed significant differences in follow-up compliance (P < 0.001 and P = 0.003, respectively) and timing of the review urea breath test (P < 0.001 and P = 0.001, respectively) between the two groups. However, no significant differences were observed in the H. pylori eradication rates (95.8% vs. 93.8%, P = 0.529) in the PP analysis, or AEs incidence (25.4% vs. 28.3%, P = 0.603) between the two groups. Conclusion: This study demonstrated the novel application of the DTD model in the treatment of H. pylori infection, which enabled patients to develop habitual medication-taking behaviors without physician intervention. [ABSTRACT FROM AUTHOR]

INTRODUCTION Few studies have examined the effect of feedback based on oral-malodor measurements on the motivation to quit smoking. Therefore, this study examined whether oral-malodor measurements were associated with the intention to quit smoking. METHODS This retrospective, uncontrolled before-after study invited smokers to a workplace health event in 2019 and 2020 to motivate them to quit smoking. They attended seminars on oral health and smoking cessation aids, and then underwent respiratory function and oral-malodor measurements using exhaled and oral cavity air, respectively. Intention to quit smoking was evaluated by answers to questions regarding the intention to quit in the next 1 or 6 months in questionnaires collected before and after the event. This study analyzed 241 men aged 20-54 years (mean: 33.2 ± 10.5) to examine factors associated with the intention to quit in multivariable logistic regression analyses for age, tobacco type (cigarettes and heated-tobacco products), and category of tobacco consumption. RESULTS Before the event, 8.7%, 17.0%, and 74.3% of smokers had intended to quit in the next month, the next six months, or had no intention to quit, respectively. After the event, the respective percentages were 17.8%, 26.6%, and 55.6%. A higher methyl mercaptan concentration, a volatile sulfide component of oral malodor, was significantly associated with the intention to quit in the next month (adjusted odds ratio, AOR=4.24; 95% CI: 1.52-11.8, p=0.006). The participants with higher daily tobacco consumption were less likely to acquire the intention to quit in the next six months (A0R=0.37; 95% CI: 0.15-0.92, p=0.032). Other variables, such as lung age deficit, exhaled CO concentration, and hydrogen sulfide concentration (another component of oral malodor), were not significantly associated. CONCLUSIONS Oral-malodor measurement feedback may help motivate men to quit smoking in the next 1 month rather than in the next six months. [ABSTRACT FROM AUTHOR]

Background and aims: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. Results: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29–99% in <50 years to 60–99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. Conclusion: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored. [ABSTRACT FROM AUTHOR]

Background: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. Methods: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization–time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. Results: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. Conclusions: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening. [ABSTRACT FROM AUTHOR]

A plasmonic sensing platform was developed as a noninvasive method to monitor gas-phase biomarkers related to cystic fibrosis (CF). The nanohole array (NHA) sensing platform is based on localized surface plasmon resonance (LSPR) and offers a rapid data acquisition capability. Among the numerous gas-phase biomarkers that can be used to assess the lung health of CF patients, acetaldehyde was selected for this investigation. Previous research with diverse types of sensing platforms, with materials ranging from metal oxides to 2-D materials, detected gas-phase acetaldehyde with the lowest detection limit at the µmol/mol (parts-per-million (ppm)) level. In contrast, this work presents a plasmonic sensing platform that can approach the nmol/mol (parts-per-billion (ppb)) level, which covers the required concentration range needed to monitor the status of lung infection and find pulmonary exacerbations. During the experimental measurements made by a spectrometer and by a smartphone, the sensing examination was initially performed in a dry air background and then with high relative humidity (RH) as an interferent, which is relevant to exhaled breath. At a room temperature of 23.1 °C, the lowest detection limit for the investigated plasmonic sensing platform under dry air and 72% RH conditions are 250 nmol/mol (ppb) and 1000 nmol/mol (ppb), respectively.

Given the significant cost of alcohol use disorder (AUD), identifying risk factors for alcohol seeking represents a research priority. Prominent addiction theories emphasize the role of motivation in the alcohol seeking process, which has largely been studied using preclinical models. In order to bridge the gap between preclinical and clinical studies, this study examined predictors of motivation for alcohol self-administration using a novel paradigm. Heavy drinkers (n = 67) completed an alcohol infusion consisting of an alcohol challenge (target breath alcohol = 60 mg%) and a progressive-ratio alcohol self-administration paradigm (maximum breath alcohol 120 mg%; ratio requirements range = 20-3 139 response). Growth curve modeling was used to predict breath alcohol trajectories during alcohol self-administration. K-means clustering was used to identify motivated (n = 41) and unmotivated (n = 26) self-administration trajectories. The data were analyzed using two approaches: a theory-driven test of a-priori predictors and a data-driven, machine learning model. In both approaches, steeper delay discounting, indicating a preference for smaller, sooner rewards, predicted motivated alcohol seeking. The data-driven approach further identified phasic alcohol craving as a predictor of motivated alcohol self-administration. Additional application of this model to AUD translational science and treatment development appear warranted.

Although exhaled aerosols and their patterns may seem chaotic in appearance, they inherently contain information related to the underlying respiratory physiology and anatomy. This study presented a multi-level database of simulated exhaled aerosol images from both normal and diseased lungs. An anatomically accurate mouth-lung geometry extending to G9 was modified to model two stages of obstructions in small airways and physiology-based simulations were utilized to capture the fluid-particle dynamics and exhaled aerosol images from varying breath tests. The dataset was designed to test two performance metrics of convolutional neural network (CNN) models when used for transfer learning: interpolation and extrapolation. To this aim, three testing datasets with decreasing image similarities were developed (i.e., level 1, inbox, and outbox). Four network models (AlexNet, ResNet-50, MobileNet, and EfficientNet) were tested and the performances of all models decreased for the outbox test images, which were outside the design space. The effect of continuous learning was also assessed for each model by adding new images into the training dataset and the newly trained network was tested at multiple levels. Among the four network models, ResNet-50 excelled in performance in both multi-level testing and continuous learning, the latter of which enhanced the accuracy of the most challenging classification task (i.e., 3-class with outbox test images) from 60.65% to 98.92%. The datasets can serve as a benchmark training/testing database for validating existent CNN models or quantifying the performance metrics of new CNN models. Dataset: The dataset is submitted and will be published as a supplement to this paper in the journal Data, this field will be filled by the editors of the journal. CFD Lung Diagnosis|Kaggle.Dataset License: license under (CC0, CC-BY, CC-BY-SA, CC-BYaeor-NC, etc.) [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary function tests such as spirometer and peak expiratory flow rate are the standard measures to test lung volumes and capacities; but generally there is a lack of such equipment in emergency departments. Hence there is a need for an easier, quicker and convenient outcome measure in such set-ups. Single breath count (SBC) can be a simple assessment method in such clinical settings. However no studies for normal values of SBC in young Healthy adults were found during the search for literature. Objective: The objective of this study was to estimate normal value of SBC in Healthy young adult population. Results: 100 participants were enrolled from 18-24 years of age in the study. The mean SBC was 39(±7) and 41(±9) in females and males respectively. The SBC had a significant positive correlation with age at r=0.3, p value 0.0051 and height at r=0.28, p value 0.0038. The SBC had a non-significant negative correlation with BMI and weight. Discussion: The results show that SBC was influenced significantly by gender (males>females), age and height of the individuals. However BMI and weight did not seem to influence the SBC. Conclusion: SBC is a test which is easy to perform and appears to correlate well with standard measures of pulmonary functions. We estimated the normal values of SBC in young healthy adults which can be used in the clinical set up. [ABSTRACT FROM AUTHOR]

Continuous monitoring for immunosuppressive status, infection and complications are a must for kidney transplantation (KTx) recipients. Traditional monitoring including blood sampling and kidney biopsy, which caused tremendous medical cost and trauma. Therefore, a cheaper and less invasive approach was urgently needed. We thought that a breath test has the potential to become a feasible tool for KTx monitoring. A prospective-specimen collection, retrospective-blinded assessment strategy was used in this study. Exhaled breath samples from 175 KTx recipients were collected in West China Hospital and tested by online ultraviolet photoionization time-of-flight mass spectrometry (UVP-TOF–MS). The classification models based on breath test performed well in classifying normal and abnormal values of creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and tacrolimus, with AUC values of 0.889, 0.850, 0.849 and 0.889, respectively. Regression analysis also demonstrated the predictive ability of breath test for clinical creatinine, eGFR, BUN, tacrolimus level, as the predicted values obtained from the regression model correlated well with the clinical true values (p < 0.05). The findings of this investigation implied that a breath test by using UVP-TOF–MS for KTx recipient monitoring is possible and accurate, which might be useful for future clinical screenings. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) has increasingly been shown to be related to extragastric diseases. Glycated hemoglobin A1c (HbA1c), an indicator of glycemic control, is closely linked to the event of diabetes. The purpose of this research was to analyze the association between H. pylori and HbA1c through a cohort study. Methods: The population who underwent multiple physical checkups in the physical examination center of Taizhou Hospital was included. All of them underwent urea breath test, serological examination and physical parameter measurement. Multiple regression was used for analyzing the influencing factors of HbA1c. In addition, the result of HbA1c on H. pylori infection was studied by restricted cubic spline (RCS) analysis. The triglyceride glucose (TyG) index represents the level of insulin resistance (IR) in the population. The population was classified on the basis of primary and last H. pylori infection, therefore, the variations of HbA1c and TyG index among totally different teams were investigated. Results: Multiple regression demonstrated that H. pylori was an influential factor in HbA1c. RCS analysis showed a nonlinear relationship between HbA1c and H. pylori infection. When HbA1c>5.7%, the chance of H. pylori infection was considerably enlarged. Additionally, long-term H. pylori infection increased HbA1c levels, while HbA1c levels decreased after H. pylori eradication. Similarly, long-term H. pylori infection also increased the TyG index. Conclusion: Prediabetes increases the danger of H. pylori infection, long-term H. pylori infection increases HbA1c and IR levels, and wipeout of H. pylori could have a positive impact for glycemic control in the population. [ABSTRACT FROM AUTHOR]