Video versus Direct Laryngoscopy for Urgent Intubation of Newborn Infants.

BACKGROUND: Repeated attempts at endotracheal intubation are associated with increased adverse events in neonates. When clinicians view the airway directly with a laryngoscope, fewer than half of first attempts are successful. The use of a video laryngoscope, which has a camera at the tip of the blade that displays a view of the airway on a screen, has been associated with a greater percentage of successful intubations on the first attempt than the use of direct laryngoscopy in adults and children. The effect of video laryngoscopy among neonates is uncertain. METHODS: In this single-center trial, we randomly assigned neonates of any gestational age who were undergoing intubation in the delivery room or neonatal intensive care unit (NICU) to the video-laryngoscopy group or the direct-laryngoscopy group. Randomization was stratified according to gestational age (<32 weeks or ≥32 weeks). The primary outcome was successful intubation on the first attempt, as determined by exhaled carbon dioxide detection. RESULTS: Data were analyzed for 214 of the 226 neonates who were enrolled in the trial, 63 (29%) of whom were intubated in the delivery room and 151 (71%) in the NICU. Successful intubation on the first attempt occurred in 79 of the 107 patients (74%; 95% confidence interval [CI], 66 to 82) in the video-laryngoscopy group and in 48 of the 107 patients (45%; 95% CI, 35 to 54) in the direct-laryngoscopy group (P<0.001). The median number of attempts to achieve successful intubation was 1 (95% CI, 1 to 1) in the video-laryngoscopy group and 2 (95% CI, 1 to 2) in the direct-laryngoscopy group. The median lowest oxygen saturation during intubation was 74% (95% CI, 65 to 78) in the video-laryngoscopy group and 68% (95% CI, 62 to 74) in the direct-laryngoscopy group; the lowest heart rate was 153 beats per minute (95% CI, 148 to 158) and 148 (95% CI, 140 to 156), respectively. CONCLUSIONS: Among neonates undergoing urgent endotracheal intubation, video laryngoscopy resulted in a greater number of successful intubations on the first attempt than direct laryngoscopy. (Funded by the National Maternity Hospital Foundation; VODE ClinicalTrials.gov number, NCT04994652.).

Advances in proteomics methods for the analysis of exhaled breath condensate.

The analysis of exhaled breath condensate (EBC) demonstrates a promising avenue of minimally invasive biopsies for diagnostics. EBC is obtained by cooling exhaled air and collecting the condensation to be utilized for downstream analysis using various analytical methods. The aqueous phase of breath contains a large variety of miscible small compounds including polar electrolytes, amino acids, cytokines, chemokines, peptides, small proteins, metabolites, nucleic acids, and lipids/eicosanoids-however, these analytes are typically present at minuscule levels in EBC, posing a considerable technical challenge. Along with recent improvements in devices for breath collection, the sensitivity and resolution of liquid chromatography coupled to online mass spectrometry-based proteomics has attained subfemtomole sensitivity, vastly enhancing the quality of EBC sample analysis. As a result, proteomics analysis of EBC has been expanding the field of breath biomarker research. We present an au courant overview of the achievements in proteomics of EBC, the advancement of EBC collection devices, and the current and future applications for EBC biomarker analysis.

Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting ß-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-ß-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.

Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.

Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress. We studied primary airway epithelial cells from healthy controls (HCs) and patients with PCD with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to the fluorescently labeled antigen Dermatophagoides pteronyssinus (Derp1-f). We immunoblotted for 3-nitrotyrosine (3-NT) and for oxidative response enzymes. We measured headspace NO above primary airway cells without and with a PCD-causing genotype. We measured nNO and exhaled breath condensate (EBC) H2O2 in vivo. Apical Derp1-f was cleared from HC better than from PCD cells. DUOX1 expression was lower in HC than in PCD cells at baseline and after 24-h Derp1-f exposure. HC cells had less 3-NT and NO3- than PCD cells. However, NO consumption by HC cells was less than that by PCD cells; NO loss was prevented by superoxide dismutase (SOD) and by apocynin. nNO was higher in HCs than in patients with PCD. EBC H2O2 was lower in HC than in patients with PCD. The PCD airway epithelium does not optimally clear antigens and is subject to oxidative and nitrosative stress. Oxidation associated with antigen stasis could represent a therapeutic target in PCD, one with convenient monitoring biomarkers.NEW & NOTEWORTHY The PCD airway epithelium does not optimally clear antigens, and antigen exposure can lead to NO oxidation and nitrosative stress. Oxidation caused by antigen stasis could represent a therapeutic target in PCD, and there are convenient monitoring biomarkers.

Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test.

BACKGROUND: Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath. METHODS: This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients' baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery). RESULTS: A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123. CONCLUSIONS: Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients' response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.

Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma.

BACKGROUND: Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases. METHODS: In this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline. RESULTS: In patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). The mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001). Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.).

Type-2 inflammation and lung function decline in chronic airway disease in the general population.

BACKGROUND: It is unclear if type-2 inflammation is associated with accelerated lung function decline in individuals with asthma and chronic obstructive pulmonary disease (COPD). We tested the hypothesis that type-2 inflammation indicated by elevated blood eosinophils (BE) and fraction of exhaled nitric oxide (FeNO) is associated with accelerated lung function decline in the general population. METHODS: We included adults from the Copenhagen General Population Study with measurements of BE (N=15 605) and FeNO (N=2583) from a follow-up examination and assessed forced expiratory volume in 1 s (FEV1) decline in the preceding 10 years. Based on pre- and post-bronchodilator lung function, smoking history and asthma at follow-up examination, participants were assigned as not having airway disease, asthma with full reversibility (AR), asthma with persistent obstruction (APO), COPD, and not classifiable airflow limitation (NAL). RESULTS: FEV1 decline in mL/year increased with 1.0 (95% CI 0.6 to 1.4, p<0.0001) per 100 cells/µL higher BE and with 3.2 (95% CI 2.0 to 4.5, p<0.0001) per 10 ppb higher FeNO. Adjusted FEV1 decline in mL/year was 18 (95% CI 17 to 20) in those with BE<300 cells/µL and FeNO<20 ppb, 22 (19-25) in BE≥300 cells/µL or FeNO≥20 ppb, and 27 (21-33) in those with BE≥300 cells/µL and FeNO≥20 ppb (p for trend<0.0001). Corresponding FEV1 declines were 24 (19-29), 33 (25-40) and 44 (31-56) in AR (0.002), 26 (14-37), 36 (12-60) and 56 (24-89) in APO (0.07), 32 (27-36), 31 (24-38) and 44 (24-65) in COPD (0.46), and 27 (21-33), 35 (26-45), and 37 (25-49) in NAL (0.10), respectively. CONCLUSIONS: Type-2 inflammation indicated by elevated BE and FeNO is associated with accelerated FEV1 decline in individuals with chronic airway disease in the general population, and this association was most pronounced in an asthma-like phenotype.

Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing.

BACKGROUND& AIMS: Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. METHODS: Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. RESULTS: A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N = 66) and ≥105 CFU/mL (N = 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P < .0001) and Klebsiella (P = .0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N = 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. CONCLUSIONS: Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide-related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities.

Machine Learning-Assisted Janus Colorimetric Face Mask for Breath Ammonia Analysis.

Artificial olfactory systems have been widely used in medical fields such as in the analysis of volatile organic compounds (VOCs) in human exhaled breath. However, there is still an urgent demand for a portable, accurate breath VOC analysis system for the healthcare industry. In this work, we proposed a Janus colorimetric face mask (JCFM) for the comfortable evaluation of breath ammonia levels by combining the machine learning K-nearest neighbor (K-NN) algorithm. Such a Janus fabric is designed for the unidirectional penetration of exhaled moisture, which can reduce stickiness and ensure facial dryness and comfort. Four different pH indicators on the colorimetric array serve as recognition elements that cross-react with ammonia, capturing the optical fingerprint information on breath ammonia by mimicking the sophisticated olfactory structure of mammals. The Euclidean distance (ED) is used to quantitatively describe the ammonia concentration between 1 ppm and 10 ppm, indicating that there is a linear relationship between the ammonia concentration and the ED response (R2 = 0.988). The K-NN algorithm based on RGB response features aids in the analysis of the target ammonia level and achieves a prediction accuracy of 96%. This study integrates colorimetry, Janus design, and machine learning to present a wearable and portable sensing system for breath ammonia analysis.

Disposable Peptidoglycan-Specific Biosensor for Noninvasive Real-Time Detection of Broad-Spectrum Gram-Positive Bacteria in Exhaled Breath Condensates.

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

Internal Standard Addition System for Online Breath Analysis.

Breath analysis with secondary electrospray ionization (SESI) coupled to mass spectrometry (MS) is a sensitive method for breath metabolomics. To enable quantitative assessments using SESI-MS, a system was developed to introduce controlled amounts of gases into breath samples and carry out standard addition experiments. The system combines gas standard generation through controlled evaporation, humidification, breath dilution, and standard injection with the help of mass-flow controllers. The system can also dilute breath, which affects the signal of the detected components. This response can be used to filter out contaminating compounds in an untargeted metabolomics workflow. The system's quantitative capabilities have been shown through standard addition of pyridine and butyric acid into breath in real time. This system can improve the quality and robustness of breath data.

Combining Thermal Desorption with Selected Ion Flow Tube Mass Spectrometry for Analyses of Breath Volatile Organic Compounds.

An instrument integrating thermal desorption (TD) to selected ion flow tube mass spectrometry (SIFT-MS) is presented, and its application to analyze volatile organic compounds (VOCs) in human breath is demonstrated for the first time. The rationale behind this development is the need to analyze breath samples in large-scale multicenter clinical projects involving thousands of patients recruited in different hospitals. Following adapted guidelines for validating analytical techniques, we developed and validated a targeted analytical method for 21 compounds of diverse chemical class, chosen for their clinical and biological relevance. Validation has been carried out by two independent laboratories, using calibration standards and real breath samples from healthy volunteers. The merging of SIFT-MS and TD integrates the rapid analytical capabilities of SIFT-MS with the capacity to collect breath samples across multiple hospitals. Thanks to these features, the novel instrument has the potential to be easily employed in clinical practice.

Femtosecond Laser Ionization Mass Spectrometry for Online Analysis of Human Exhaled Breath.

A variety of organic compounds in human exhaled breath were measured online by mass spectrometry using the fifth (206 nm) and fourth (257 nm) harmonic emissions of a femtosecond ytterbium (Yb) laser as the ionization source. Molecular ions were enhanced significantly by means of resonance-enhanced, two-color, two-photon ionization, which was useful for discrimination of analytes against the background. The limit of detection was 0.15 ppm for acetone in air. The concentration of acetone in exhaled breath was determined for three subjects to average 0.31 ppm, which lies within the range of normal healthy subjects and is appreciably lower than the range for patients with diabetes mellitus. Many other constituents, which could be assigned to acetaldehyde, ethanol, isoprene, phenol, octane, ethyl butanoate, indole, octanol, etc., were observed in the exhaled air. Therefore, the present approach shows potential for use in the online analysis of diabetes mellitus and also for the diagnosis of various diseases, such as COVID-19 and cancers.

Image Sensing of Gaseous Acetone Using Secondary Alcohol Dehydrogenase-Immobilized Mesh for Exhaled Air.

Human-borne acetone is a potent marker of lipid metabolism. Here, an enzyme immobilization method for secondary alcohol dehydrogenase (S-ADH), which is suitable for highly sensitive and selective biosensing of acetone, was developed, and then its applicability was demonstrated for spatiotemporal imaging of concentration distribution. After various investigations, S-ADH-immobilized meshes could be prepared with less than 5% variation by cross-linking S-ADH with glutaraldehyde on a cotton mesh at 40 °C for 15 min. Furthermore, high activity was obtained by adjusting the concentration of the coenzyme nicotinamide adenine dinucleotide (NADH) solution added to the S-ADH-immobilized mesh to 500 µM and the solvent to a potassium phosphate buffer solution at pH 6.5. The gas imaging system using the S-ADH-immobilized mesh was able to image the decrease in NADH fluorescence (ex 340 nm, fl 490 nm) caused by the catalytic reaction of S-ADH and the acetone distribution in the concentration range of 0.1-10 ppm-v, including the breath concentration of healthy people at rest. The exhaled breath of two healthy subjects at 6 h of fasting was quantified as 377 and 673 ppb-v, which were consistent with the values quantified by gas chromatography-mass spectrometry.

ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction (F ENO50 ).

BACKGROUND: Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s-1 (F ENO50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO50 . METHODS: Available individual F ENO50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of "healthy" were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. RESULTS: Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO50 (R2=0.12). F ENO device was neccessary as a predictor of F ENO50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. CONCLUSION: Available F ENO50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.

Testing for Helicobacter pylori in an era of antimicrobial resistance.

Antimicrobial resistance in Helicobacter pylori has reached alarming levels and is compromising traditional empiric treatment of H. pylori. Antimicrobial susceptibility testing is routinely performed for infectious diseases when there is a risk of resistance and is now recommended to guide therapy for H. pylori. This mini-review overviews the current diagnostics for H. pylori with a focus on tests that enable susceptibility-guided treatment, including molecular tests performed directly on stool and endoscopically collected specimens.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV-associated chronic lung disease.

OBJECTIVES: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. METHODS: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. RESULTS: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103). CONCLUSION: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation.

A study of 9 common breath VOCs in 504 healthy subjects using PTR-TOF-MS.

INTRODUCTION: This study employs Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) to analyze exhaled breath profiles of 504 healthy adults, focusing on nine common volatile organic compounds (VOCs): acetone, acetaldehyde, acetonitrile, ethanol, isoprene, methanol, propanol, phenol, and toluene. PTR-MS offers real-time VOC measurement, crucial for understanding breath biomarkers and their applications in health assessment. OBJECTIVES: The study aims to investigate how demographic factors-gender, age, and smoking history-affect VOC concentrations in exhaled breath. The objective is to enhance our understanding of breath biomarkers and their potential for health monitoring and clinical diagnosis. METHODS: Exhaled breath samples were collected using PTR-MS, measuring concentrations of nine VOCs. The data were analyzed to discern distribution patterns across demographic groups. RESULTS: Males showed higher average VOC levels for certain compounds. Propanol and methanol concentrations significantly increased with age. Smoking history influenced VOC levels, with differences among non-smokers, current smokers, and ex-smokers. CONCLUSION: This research provides valuable insights into demographic influences on exhaled VOC profiles, emphasizing the potential of breath analysis for health assessment. PTR-MS's real-time measurement capabilities are crucial for capturing dynamic VOC changes, offering advantages over conventional methods. These findings lay a foundation for advancements in non-invasive disease detection, highlighting the importance of considering demographics in breath biomarker research.