Could exhaled methane be used as a possible indicator for hemodynamic changes in trauma induced hemorrhagic shock? Scientific basis supported by a case study.

INTRODUCTION: Identification of severe blood loss and hemorrhagic shock in polytrauma patients poses a key challenge for trauma teams across the world, as there are just a few objective parameters, on which clinicians can rely. We investigated the relationship between exhaled air methane (CH4) concentration and blood loss in a polytrauma patient. Decreased blood flow in the superior mesenteric artery (SMA) is one of the first compensatory responses to blood loss. Gases produced by the anaerobic flora of the intestinal segment supplied by the SMA are the primary source of exhaled CH4, which diffuses through the intestinal microvessels into the circulation and is finally eliminated through the lungs. We hypothesized that diminution of exhaled CH4 indicates blood loss and tested our theory in a severely injured patient. METHODS: Exhaled CH4 concentrations of a severely injured patient were measured using a photoacoustic spectroscope (PAS) attached to the exhalation side of the breathing circuit. The primary objective was to investigate the relationship between exhaled CH4 and conventional indicators of hemorrhage including hemoglobin (Hb) levels, base deficit (BD) values and vital parameters (heart rate and systolic blood pressure) in the early phase of in-hospital care (first 4 h). RESULTS: A severely injured patient was admitted with unstable hemodynamic parameters and incomplete left lower limb amputation, (Injury Severity Score: 38, 74/36 mmHg, 76 bpm). At the time of arrival, considerably lower CH4 levels were detected (22,800 PAU) in the exhaled air. During the first 4 h fluid and massive blood resuscitation, the exhaled CH4 levels were continuously rising in parallel with Htc and Hb values. Corresponding to these changes, BD values displayed a decreasing tendency. DISCUSSION: Our study was conducted to characterize the changes in exhaled air CH4 concentration in response to hemorrhagic shock and to provide data on a viable clinical use of an experimental technique. According to our results, the real-time detection of exhaled air CH4 concentration is an applicable and promising technique for the early detection of bleeding and hemorrhagic shock in severely injured patients. Further research on large sample size and refinement of the PAS technique is required.

Identification of Exhaled Metabolites Correlated with Respiratory Function and Clinical Features in Adult Patients with Cystic Fibrosis by Real-Time Proton Mass Spectrometry.

Cystic fibrosis (CF) is a hereditary disease characterized by the progression of respiratory disorders, especially in adult patients. The purpose of the study was to identify volatile organic compounds (VOCs) as predictors of respiratory dysfunction, chronic respiratory infections of Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, and VOCs associated with severe genotype and highly effective modulator treatment (HEMT). Exhaled breath samples from 102 adults with CF were analyzed using PTR-TOF-MS, obtained during a forced expiratory maneuver and normal quiet breathing. Using cross-validation and building gradient boosting classifiers (XGBoost), the importance of VOCs for functional and clinical outcomes was determined. The presence of the previously identified VOCs indole, phenol, and dimethyl sulfide were metabolic outcomes associated with impaired respiratory function. New VOCs associated with respiratory disorders were methyl acetate, carbamic acid, 1,3-Pentadiene, and 2,3-dimethyl-2-butene; VOCs associated with the above mentioned respiratory pathogens were non-differentiable nitrogen-containing organic compounds m/z = 47.041 (CH5NO)+ and m/z = 44.044 (C2H5NH+), hydrocarbons (cyclopropane, propene) and methanethiol; and VOCs associated with severe CFTR genotype were non-differentiable VOC m/z = 281.053. No significant features associated with the use of HEMT were identified. Early non-invasive determination of VOCs as biomarkers of the severity of CF and specific pathogenic respiratory flora could make it possible to prescribe adequate therapy and assess the prognosis of the disease. However, further larger standardized studies are needed for clinical use.

Generating pooled quality control samples of volatile organic compounds.

Untargeted analysis of volatile organic compounds (VOCs) from exhaled breath and culture headspace are influenced by several confounding factors not represented in reference standards. In this study, we propose a method of generating pooled quality control (QC) samples for untargeted VOC studies using a split-recollection workflow with thermal desorption tubes. Sample tubes were desorbed and split from each sample and recollected onto a single tube, generating a pooled QC sample. This QC sample was then repeatedly desorbed and recollected with a sequentially lower split ratio allowing injection of multiple QC samples. We found pooled QC samples to be representative of complex mixtures using principal component analysis and may be useful in future longitudinal, multi-centre, and validation studies to assess data quality and adjust for batch effects.

Exhaled breath condensate (EBC) in respiratory diseases: recent advances and future perspectives in the age of omic sciences.

Exhaled breath condensate (EBC) is used as a promising noninvasive diagnostic tool in the field of respiratory medicine. EBC is achieved by cooling exhaled air, which contains aerosolized particles and volatile compounds present in the breath. This method provides useful information on the biochemical and inflammatory state of the airways. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, EBC analysis can reveal elevated levels of biomarkers such as hydrogen peroxide, nitric oxide and various cytokines, which correlate with oxidative stress and inflammation. Furthermore, the presence of certain volatile organic compounds in EBC has been linked to specific respiratory conditions, potentially serving as disease-specific fingerprints. The noninvasive nature of EBC sampling makes it particularly useful for repeated measures and for use in vulnerable populations, including children and the elderly. Despite its potential, the standardization of collection methods, analytical techniques and interpretation of results currently limits its use in clinical practice. Nonetheless, EBC holds significant promise for improving the diagnosis, monitoring and therapy of respiratory diseases. In this tutorial we will present the latest advances in EBC research in airway diseases and future prospects for clinical applications of EBC analysis, including the application of the Omic sciences for its analysis.

Electronic Nose Analysis of Exhaled Breath Volatile Organic Compound Profiles during Normoxia, Hypoxia, and Hyperoxia.

This study investigates volatile organic compound (VOC) profiles in the exhaled breath of normal subjects under different oxygenation conditions-normoxia (FiO2 21%), hypoxia (FiO2 11%), and hyperoxia (FiO2 35%)-using an electronic nose (e-nose). We aim to identify significant differences in VOC profiles among the three conditions utilizing principal component analysis (PCA) and canonical discriminant analysis (CDA). Our results indicate distinct VOC patterns corresponding to each oxygenation state, demonstrating the potential of e-nose technology in detecting physiological changes in breath composition (cross-validated accuracy values: FiO2 21% vs. FiO2 11% = 63%, FiO2 11% vs. FiO2 35% = 65%, FiO2 21% vs. FiO2 35% = 71%, and p < 0.05 for all). This research underscores the viability of breathomics in the non-invasive monitoring and diagnostics of various respiratory and systemic conditions.

Exhaled volatile organic compounds (VOCs) for prediction of asthma exacerbation in children.

OBJECTIVES: To find possible relationship between asthma exacerbation and metabolomic profile of airways, assessed by non-invasive method - free volatile organic compounds (VOCs) in exhaled air in children. MATERIAL AND METHODS: The study included 80 children aged 4-18 years with asthma: 42 children with a min. 3 asthma exacerbations in the past 12 months, and 38 children without a history of exacerbations in the past year. During the study visit, each patient was examined, medical history (including information regarding atopy and eosinophil blood count) was taken, spirometry and fractional exhaled nitric oxide (FeNO) were tested, an exhaled air sample was taken to test for the presence of VOCs, and the patient also completed standardized form - Asthma Control Questionnaire. Volatile organic compounds were measured by combined gas chromatography coupled to mass spectrometry. RESULTS: The obtained results of VOCs were correlated with the history of the disease. The 2 gas profiles were defined and they formed 2 clinically distinct clusters (p = 0.085). Cluster 2 was characterized for children with a higher number of bronchial asthma exacerbations and worse lung function parameters (predicted percentage forced expiratory volume in 1 s [FEV1] [p = 0.023], FEV1/ forced vital capacity ratio [FVC] [p = 0.0219]). The results were independent of the age, sex, BMI, atopy (house dust mite allergy) and eosinophil blood count. CONCLUSIONS: The study findings suggest that a relative group of gases may be a useful predictor of having asthma exacerbations in children. Additionally, a single FeNO value was unlikely to be clinically useful in predicting asthma exacerbations in children. The VOCs profile reflecting the metabolism of the airway epithelium and local microbiota was associated with the course of asthma, which strongly justifies further prospective validation studies. Int J Occup Med Environ Health. 2024;37(3):351-59.

Effect of a prolonged slow expiration technique on 24-h food intake in children hospitalized for moderate bronchiolitis: a randomized controlled trial.

BACKGROUND: Chest physiotherapy for airway clearance is not recommended in children hospitalized with bronchiolitis. The updated Cochrane meta-analysis suggests that slow expiratory techniques could slightly improve clinical severity, but the evidence certainty is low and the clinical significance of this change is unknown. We investigated whether the prolonged slow expiration technique (PSET) would impact the 24-h food intake of these children. METHODS: We conducted a two-arm double-blind randomized controlled trial. Hospitalized children aged from 1 to 12 months, bottle-fed or diversified and referred for airway clearance were included. Both groups received upper airway clearance at inclusion and standard treatments. The experimental group received PSET including rhinopharyngeal unclogging and targeted unprovoked cough. The primary outcome was the 24-h food intake. Clinical severity, vomit episodes and sleep quality were also recorded. An ordinary least squares linear regression for quantitative variables was modelled for between-group comparisons. RESULTS: From January 9, 2019, to December 1, 2022, 42 children were randomized with a 1:1 ratio (mean age: 5.0 (± 2.9) months). The 24-h food intake did not differ between groups (estimate: 1.8% (95%CI -7.0 to 10.6); p = 0.68). PSET had no effect on SpO2, clinical severity, RR and HR at the follow-up assessments (5 min, 30 min and 24 h after intervention), nor on the number of vomit episodes, total sleep time and SpO2 during sleep. CONCLUSIONS: PSET did not affect food intake or the 24-h course of bronchiolitis more than standard treatment in children hospitalized for moderate bronchiolitis. TRIAL REGISTRATION: NCT03738501  registered on 13/11/2018, Slow Expiratory Technique to Improve Alimentation in Children With Bronchiolitis (BRONCHIOL-EAT); https://classic. CLINICALTRIALS: gov/ct2/show/NCT03738501.

Reference values for exhaled nitric oxide in healthy children aged 6-18 years in China: a cross-sectional, multicenter clinical study.

BACKGROUND: The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6-18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. METHODS: We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6-18. All persons were studied after obtaining informed consent from children and their parents. RESULTS: The mean FeNO50 of 5949 Chinese children and adolescents aged 6-18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6-11 age group, age and height were correlated with the logarithm of FeNO50 (P < 0.001, P < 0.05). There was no significant correlation between the logarithm of FeNO200 and gender, age, height and BMI (all P > 0.05). The logarithm of CaNO was correlated with gender (P < 0.05). In the 12-18 age group, gender, height, and region were correlated with the logarithm of FeNO50 (all P < 0.001). There was only a weak correlation between the logarithm of FeNO200 and height (P < 0.001). The logarithm of CaNO was negatively correlated with age (P < 0.05). CONCLUSIONS: Higher FeNO50, FeNO200 and CaNO values were found in healthy children and adolescents in China compared with foreign reports, and is affected by age, height, gender, and region. This study provides useful references for clinical application of eNO in children, especially Asian children.

Deep-Learning-Based Blood Glucose Detection Device Using Acetone Exhaled Breath Sensing Features of α-Fe2O3-MWCNT Nanocomposites.

Owing to the correlation between acetone in human's exhaled breath (EB) and blood glucose, the development of EB acetone gas-sensing devices is important for early diagnosis of diabetes diseases. In this article, a noninvasive blood glucose detection device through acetone sensing in EB, based on an α-Fe2O3-multiwalled carbon nanotube (MWCNT) nanocomposite, was successfully developed. Different amounts of α-Fe2O3 were added to the MWCNTs by a simple solution method. The optimized acetone gas sensor showed a response of 5.15 to 10 ppm acetone gas at 200 °C. Also, the fabricated sensor showed very good sensing properties even in an atmosphere with high relative humidity. Since the EB has high humidity, the proposed sensor is a promising device to exactly detect the amount of acetone in EB with high humidity. The sensor was powered by a 3200 mAh battery with the possibility of charging using mains electricity. To increase the reliability and calibration of the sensing device, a practical test was taken to detect acetone EB from 50 volunteers, and a deep learning algorithm (DLA) was used to detect the effect of various factors on the amount of acetone in each person's acetone EB. The proposed device with ±15 errors had almost 85% correct responses. Also, the proposed device had excellent response, short response time, good selectivity, and good repeatability, leading it to be a suitable candidate for noninvasive blood glucose sensing.

High-quality identification of volatile organic compounds (VOCs) originating from breath.

INTRODUCTION: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers. OBJECTIVES: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population. METHODS: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy® OMNI® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching. RESULTS: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes. CONCLUSIONS: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization.

Exhaled Volatile Organic Compounds Detection in Pneumonia Screening: A Comprehensive Meta-analysis.

BACKGROUND: Pneumonia is a common lower respiratory tract infection, and early diagnosis is crucial for timely treatment and improved prognosis. Traditional diagnostic methods for pneumonia, such as chest imaging and microbiological examinations, have certain limitations. Exhaled volatile organic compounds (VOCs) detection, as an emerging non-invasive diagnostic technique, has shown potential application value in pneumonia screening. METHOD: A systematic search was conducted on PubMed, Embase, Cochrane Library, and Web of Science, with the retrieval time up to March 2024. The inclusion criteria were diagnostic studies evaluating exhaled VOCs detection for the diagnosis of pneumonia, regardless of the trial design type. A meta-analysis was performed using a bivariate model for sensitivity and specificity. RESULTS: A total of 14 diagnostic studies were included in this meta-analysis. The pooled results demonstrated that exhaled VOCs detection had a combined sensitivity of 0.94 (95% CI: 0.92-0.95) and a combined specificity of 0.83 (95% CI: 0.81-0.84) in pneumonia screening, with an area under the summary receiver operating characteristic (SROC) curve (AUC) of 0.96. The pooled diagnostic odds ratio (DOR) was 104.37 (95% CI: 27.93-390.03), and the pooled positive and negative likelihood ratios (LR) were 8.98 (95% CI: 3.88-20.80) and 0.11 (95% CI: 0.05-0.22), indicating a high diagnostic performance. CONCLUSION: This study highlights the potential of exhaled VOCs detection as an effective, non-invasive screening method for pneumonia, which could facilitate future diagnosis in pneumonia. Further high-quality, large-scale studies are required to confirm the clinical utility of exhaled VOCs detection in pneumonia screening. STUDY REGISTRATION: PROSPERO, Review no. CRD42024520498.

Difference in expiratory flow limitations development in normoxia and hypoxia in healthy individuals.

The present study investigated the maintenance/repeatability of expiratory flow limitation (EFL) between normoxia and hypoxia. Fifty-one healthy active individuals (27 men and 24 women) performed a lung function test and a maximal incremental cycling test in both normoxia and hypoxia (inspired oxygen fraction = 0.14) on two separate visits. During exercise in normoxia, 28 participants exhibited EFL (55 %). In hypoxia, another cohort of 28 participants exhibited EFL. The two groups only partly overlapped. Individuals with EFL only in normoxia reported lower maximal ventilation values in hypoxia than in normoxia (n=5; -13.5 ± 7.8 %) compared to their counterparts with EFL only in hypoxia (n=5; +6.7 ± 6.3 %) or without EFL (n=18; +5.1 ± 10.3 %) (p=0.004 and p<0.001, respectively). EFL development may be induced by different mechanisms in hypoxia vs. normoxia since the individuals who exhibited flow limitation were not the same between the two environmental conditions. This change seems influenced by the magnitude of the maximal ventilation change.

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

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

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

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

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

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

Breath and Sputum Analyses in Asthmatic Patients: An Overview.

Recent advancements in asthma management include non-invasive methodologies such as sputum analysis, exhaled breath condensate (EBC), and fractional exhaled nitric oxide (FeNO). These techniques offer a means to assess airway inflammation, a critical feature of asthma, without invasive procedures. Sputum analysis provides detailed insights into airway inflammation patterns and cellular composition, guiding personalized treatment strategies. EBC collection, reflecting bronchoalveolar lining fluid composition, provides a non-invasive window into airway physiology. FeNO emerges as a pivotal biomarker, offering insights into eosinophilic airway inflammation and aiding in asthma diagnosis, treatment monitoring, and the prediction of exacerbation risks. Despite inherent limitations, each method offers valuable tools for a more comprehensive assessment of asthma. Combining these techniques with traditional methods like spirometry may lead to more personalized treatment plans and improved patient outcomes. Future research is crucial to refine protocols, validate biomarkers, and establish comprehensive guidelines in order to enhance asthma management with tailored therapeutic strategies and improved patient outcomes.

Volatile organic compounds in cancer and exhaled breath detection technology.

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

A smart mask for exhaled breath condensate harvesting and analysis.

Recent respiratory outbreaks have garnered substantial attention, yet most respiratory monitoring remains confined to physical signals. Exhaled breath condensate (EBC) harbors rich molecular information that could unveil diverse insights into an individual's health. Unfortunately, challenges related to sample collection and the lack of on-site analytical tools impede the widespread adoption of EBC analysis. Here, we introduce EBCare, a mask-based device for real-time in situ monitoring of EBC biomarkers. Using a tandem cooling strategy, automated microfluidics, highly selective electrochemical biosensors, and a wireless reading circuit, EBCare enables continuous multimodal monitoring of EBC analytes across real-life indoor and outdoor activities. We validated EBCare's usability in assessing metabolic conditions and respiratory airway inflammation in healthy participants, patients with chronic obstructive pulmonary disease or asthma, and patients after COVID-19 infection.

A Prototype of Graphene E-Nose for Exhaled Breath Detection and Label-Free Diagnosis of Helicobacter Pylori Infection.

Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis.