Volatile compounds, abundant in breath, can be used to accurately diagnose and monitor a range of medical conditions. This offers a non-invasive, low-cost approach with screening applications; however, uptake of this diagnostic approach has been limited by conflicting published outcomes. Most published reports rely on large scale screening of the public, at single time points and without reference to ambient air. Here, we present a novel approach to volatile sampling from cellular headspace and mouse breath that incorporates multi-time point analysis and ambient air subtraction revealing compound flux as an effective proxy of active metabolism. This approach to investigating breath volatiles offers a new avenue for disease biomarker discovery and diagnosis. Using gas chromatography mass spectrometry (GC/MS), we focus on low molecular weight, metabolic substrate/by-product compounds and demonstrate that this non-invasive technique is sensitive (reproducible at ~1 µg cellular protein, or ~500,000 cells) and capable of precisely determining cell type, status and treatment. Isolated cellular models represent components of larger mammalian systems and we show that stress- and pathology-indicative compounds are detectable in mice, supporting further investigation using this methodology as a tool to identify volatile targets in human patients.

ecent interest in breath methane has demonstrated considerable growth, with a 400% increase in publications per year between 2010 and 2020 compared to the previous decade. This surge has been facilitated by advancements in measurement techniques that have improved both the precision and ease of breath methane analysis. Consequently, there has been a growing appreciation for both the routes of production as well as the physiological effects of methane within the human body, shifting from a perspective of methane as an end-product of GI microbiota to viewing it as a potentially biologically active molecule with exciting potential implications for endogenous processes. The breath methane field stands at a pivotal juncture, where new technologies enable real-time, repeated measures of breath methane for the first time, paving the way for novel insights into personalized methane levels and their interplay with health. This review explores the origins, physiological effects, and measurement techniques of breath methane, highlighting potential pathways for future research.

The review is devoted to the physical, chemical and technological aspects of the breath-figures self-assembly process. Main stages of the process and the impact of the polymer architecture and physical parameters of the breath-figures self-assembly on the eventual pattern are covered. The review is focused on the hierarchy of spatial and temporal scales inherent for the breath-figures self-assembly. Multi-scale patterns arising from the process are addressed. The characteristic spatial lateral scales of patterns vary from nanometers to dozens of micrometers. The temporal scales of the process span from micro-seconds to seconds. The qualitative analysis performed in the paper demonstrates that the process is mainly governed by the interfacial phenomena, whereas the impact of inertia and gravity is negligible. Characterization and applications of polymer films manufactured with breath-figures self-assembly are discussed.

Objectives: Valsalva maneuver is performed during strength physical exercises, because it stabilizes the torso through increased intra-abdominal pressure. By contrast, yoga practitioners are discouraged from Valsalva. Instead, they use ujjayi breath, which consists of unstopped breathing through the narrowed glottis. Methods: This study was an observational research performed in healthy participants. The aim of this study was to evaluate veins in the groin area during different types of breathing. We examined 10 healthy people in the standing body position during: a) normal breathing b) Valsalva maneuver c) ujjayi breath. We measured the cross-sectional areas of the femoral and the great saphenous veins in the proximity to the sapheno-femoral junction. Results: In comparison with normal breathing, there were only slight dilatations of examined veins during Valsalva and ujjayi. The cross-sectional area of femoral vein increased by 7-9% during Valsalva, and 2-4% during ujjayi; cross-sectional area of the great saphenous vein increased by 17-18% during Valsalva and 15-16% during ujjayi. In all participants the terminal and preterminal valves of the great saphenous vein were competent. However, Valsalva maneuver was associated with complete closure of the terminal valve, while during ujjayi breath this valve was opening and closing, following the breathing. Conclusions: In the standing body position both Valsalva and ujjayi breath have minimal effect on cross-sectional areas of the veins in the groin. On the other hand, ujjayi breath allows for undisturbed flow through the sapheno-femoral junction, while Valsalva interrupts this flow, with blood stagnation distally from the terminal valve.

SIBO is a pathology of the small intestine and may predispose individuals to a range of nutritional deficiencies. Very little is known whether specific subtypes of SIBO, such as hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane –dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p<0.001), low serum ferritin (p=0.001) and low fiber intake (p=0.001). The M+ group was correlated with high serum folic acid (p=0.002) and low intakes of fiber (p=0.001) and lactose (p=0.002). The H+ group was associated with low lactose intake (p=0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of deficiencies in the body. Conversely, specific dietary patterns may predispose to the development of a SIBO subtype. The assessment of nutritional status and diet, along with diagnosis of SIBO substype, are believed to be key components of SIBO therapy.

Existing approaches to identifying predictive T-cell epitopes have traditionally utilized either 2-digit HLA super-families or more commonly autologous HLA alleles to facilitate the predictions, but frequently they may not consider their representation within a population. Here we propose a modification to this concept whereby subsets of individuals are selected for their specific HLA allele profiles and the representation they provide within a given population. Using this targeted approach to HLA selection and the linkages to specific individuals may enable the design of restricted experimental strategies.

A major limitation of near-infrared spectroscopy (NIRS) is its high sensitivity to the scalp and low sensitivity to the brain of adult humans. In the present work we use multi-distance hyperspectral NIRS (hNIRS) to investigate the optimal source-detector distances, range of wavelengths, and analysis techniques to separate cerebral responses to 30-s breath holds (BHs) from the responses in the superficial tissue layer in healthy adult humans. We observed significant responses to BHs in the scalp hemodynamics. Cerebral responses to BHs were detected in the cytochrome C oxidase redox (rCCO) at 4 cm without using data from the short-distance channel. Using the data from the 1 cm channel in the two-layer regression algorithm showed that hemodynamic and rCCO responses also occurred at 3cm. We found that the waveband 700-900 nm was optimal for the detection of cerebral responses to BHs in adults.

Deep inhalation breath hold (DIBH) has become a valuable technique in left breast cancer radiotherapy, offering the possibility to reduce radiation exposure to organs at risk (OARs) and minimize the risk of cardiac complications. The treatment method involves patients stopping breathing during irradiation to temporarily distance the heart from the radiation field, reducing potential cardiac and other complications. Research shows that DIBH reduces the radiation dose to the heart and lungs. However, the effectiveness of DIBH is determined by a variety of factors, including the patient's training, cooperation, anatomical features, age and choice of radiotherapy technique. Additionally, cardiovascular risk factors: diabetes, smoking, hypertension can affect the effectiveness and potential complications of DIBH. Moreover, lack of consent, fear, anxiety, depression and comorbid psychiatric disorders disqualify some patients from the DIBH treatment method. Careful patient selection, comprehensive training and optimization of treatment parameters are essential to maximize the benefits of DIBH while minimizing potential side effects. DIBH enhancement techniques, such as IMRT or VMAT, also have an important role to play. The purpose of this review article is to summarize the factors affecting the efficacy and side effects of DIBH in radiation therapy for left breast cancer, with the aim of optimizing its clinical application while minimizing side effects.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

Exhaled breath condensate (EBC) sample analysis is an entirely non-invasive novel sample collection method that is fast, easy to perform, and effort-appeared independent. EBC samples can be very useful in identifying the biomarkers of many diseases. This review provides an updated overview of EBC pH disturbances in different disorders as well as physiological levels among healthy individuals since 2012. Our meta-analysis addresses some of the key questions related to sample processing before pH measurement and discusses various methods of condensate standardization that can be employed prior to conducting a pH assay. Given the recent widespread interest in research into the use of EBC to identify biomarkers, it is necessary to establish a pathway leading from analytical methods for biomarker evaluation using EBC pH to clinical applications of this technology. This review fills a gap in the literature and attempts to connect theory to practical analytical approaches to analyzing EBC samples and making critical treatment-related decisions next to the patient's bed.

Breath volatile organic compound analysis is a non-invasive tool for assessing health status; the compositional profile of these compounds in the breath of patients with chronic kidney disease is believed to change with decreasing renal function. We aimed to identify breath volatile organic compounds for recognizing patients with chronic kidney disease. Using thermal desorption-gas chromatography-mass spectrometry, untargeted analysis of breath markers was performed using breath samples of healthy controls (n=18) versus non-dialysis (n=21) and hemodialysis (n=12) patients with chronic kidney disease in this cross-sectional study. A total of 303 volatile organic compounds alongside 12 clinical variables were used to determine the breath volatile organic compound profile. Metabolomic analysis revealed that age, systolic blood pressure, and fifty-eight breath volatile organic compounds differed significantly between the chronic kidney disease group (non-dialysis + hemodialysis) and healthy controls. Thirty-six volatile organic compounds and two clinical variables that showed significant associations with chronic kidney disease in the univariate analysis were further analyzed. Different spectras of breath volatile organic compounds between the control and chronic kidney disease groups were obtained. Multivariate model incorporating age, 2-methyl-pentane, and cyclohexanone showed high performance (accuracy, 86%) in identifying patients with chronic kidney disease, with odds ratios (95% confidence interval) P-values of 0.18 (0.07-2.49) 0.013; 2.10 (0.94-2.24) 0.025; and 2.31 (0.88–2.64) 0.008, respectively. Hence, renal dysfunction-associated characteristic profiles of breath volatile organic substances can be used as non-invasive markers to screen for chronic kidney disease.

Yogic and meditative traditions have long held that the fluctuations of the breath and the mind are intimately related. While respiratory modulation of cortical activity and attentional switching are established, the extent to which electrophysiological markers of attention exhibit synchronization with respiration is unknown. To this end, we examined 1) frontal midline theta-beta ratio, an indicator of attentional control state known to correlate with mind wandering episodes and functional connectivity of the executive control network; 2) pupil diameter (PD), a known proxy measure of locus coeruleus (LC) noradrenergic activity; and 3) respiration for evidence of phase synchronization and information transfer (multivariate Granger causality) during quiet restful breathing. Our results indicate that both TBR and PD are simultaneously synchronized with the breath, suggesting an underlying oscillation of an attentionally relevant electrophysiological index that is phase-locked to the respiratory cycle which could have the potential to bias the attentional system into switching states. We highlight the LC’s pivotal role as a coupling mechanism between respiration and TBR, and elaborate on its dual functions as both a chemosensitive respiratory nucleus and a pacemaker of the attentional system. We further suggest that an appreciation of the dynamics of this weakly coupled oscillatory system could help deepen our understanding of the traditional claim of a relationship between breathing and attention.

Many patients with Coronavirus disease 2019 (COVID-19) suffer from shortness of breath and severe chest pain. Here we report successful therapy of a patient with diagnosis of COVID-19, severe chest pain and significant shortness of breath, using radial extracorporeal shock wave therapy (rESWT). The latter started seven days after beginning of symptoms and drug therapy without success, and involved daily application of 15.000 to 20.000 radial extracorporeal shock waves over the intercostal muscles as well as the paravertebral muscles of the thoracic and lumbar spine, diaphragm and flanks. Immediately after the first rESWT session the patient experienced significant pain relief and improvement of breathing. Four days later the pain had completely subsided and breathing was largely normalized. This type of noninvasive, non-pharmacologic treatment could help many COVID-19 patients or patients who still suffer from breathing problems weeks after having been infected with SARS-CoV-2, giving them back quality of life.

One third of fatal car accidents and so much tragedies are due to alcohol abuse. These sad numbers could be mitigated if everyone had access to a breathalyzer anytime and anywhere. Having a breathalyzer built into a phone or a wearable could be the way to get around the reluctance to carry a separate device. Towards this goal, we propose an inexpensive breathalyzer that could be integrated in the screen of mobile devices. Our technology is based on the evaporation rate of the fog produced by the breath on the phone screen, which increases as a function of the breath alcohol content. The device simply uses a photodiode placed on the side of the screen to measure the signature of the scattered light intensity from the phone display that is guided through the stress layer of the Gorilla glass screen. A part of the display light is coupled to the stress layer via the evanescent field induced at the edge of the breath microdroplets. We demonstrate that the intensity signature measured at the detector can be linked to the blood alcohol content. We fabricated a prototype in a smartphone case powered by the phone’s battery, controlled by an application software installed in the smartphone and tested it in real-world environments. Limitations and future work toward a fully operational device are discussed.

In the present work a novel, portable and innovative eNose composed of a surface acoustic wave (SAW) sensor array based ZIF-8, and ZIF-67 nanocrystals (pure and combined with gold nanoparticles) as sensitive layers has been tested as a non-invasive system to detect and differentiate disease markers, such as acetone, ethanol and ammonia, related with early diagnosis of diabetes mellitus through exhaled breath. The sensors have been prepared by spin coating, achieving continuous and homogenous sensitive layers. Low concentrations (5 ppm, 10 ppm and 25ppm) of the marker analytes were measured, obtaining high sensitivities, good reproducibility, short time response and fast signal recovery.

Bacterial infection of the lower respiratory tract frequently occurs in mechanically ventilated pa-tients and may develop into life-threatening conditions. Yet existing diagnostic methods have moderate sensitivity and specificity, which results in the overuse of broad-spectrum antibiotics administrated prophylactically. This study aims to evaluate the suitability of volatile bacterial me-tabolites for breath-based test diagnosing Ventilation-Associated Pneumonia (VAP). The in vitro experiments with pathogenic microorganisms most prevalent in VAP patients (i.e., Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) were performed to identify bacteria-derived metabolites using specially designed cultivation system enabling headspace sam-pling for GC-MS analysis. Thirty-nine compounds were found to be significantly metabolized by tested species and, therefore, selected for monitoring in the exhaled breath of critically ill, me-chanically ventilated (MV) patients. The emission of volatiles from medical respiratory devices was investigated to estimate the risk of spoiling breath results with exogenous pollutants. Bacterial metabolites were then evaluated to differentiate VAP patients from non-infected MV controls using receiver operating characteristic (ROC) analysis, with AUC, sensitivity, and specificity calculated. Nine bacterial metabolites that passed verification through a non-parametric ANOVA test for significance and LASSO penalization were identified as key discriminators between VAP and non-VAP patients. The diagnostic model achieved an AUC of 0.893, with sensitivity and specificity values of 87% and 82.4%, respectively, being competitive with traditional methods. Further vali-dation could solidify its clinical utility in critical care settings.

Hierarchical honeycomb patterns were manufactured with the breath-figures self-assembly by drop-casting on the silicone-oil lubricated glass substrates. Silicone oil promoted spreading of the polymer solutions. The process was carried out with the industrial grade polystyrene and polystyrene with the molecular weight Mw=35.000. Both of polymers gave rise to the patterns, built from micro- and nano-scaled pores. Ordering of the pores was quantified with the Voronoi tessellations and calculating the Voronoi entropy. Measurement of the apparent contact angles evidenced the Cassie - Baxter wetting regime of the porous films.

Flexible humidity sensors (FHS) with fast response and durability to high-humidity environment are highly desirable for practical applications. Herein, an FHS based on crosslinked sodium alginate (SA) and MXene was fabricated, which exhibited high sensitivity (impedance varied from 107 to 105 Ω between 10% and 90% RH), good selectivity, prompt response (response/recover time of 4 s/11 s), high sensing linearity (R2 = 0.992) on a semi-logarithmic scale, relatively small hysteresis (~5% RH), good repeatability, and good resistance to high humid environment (negligible change in sensing properties after placed in 98% RH over 24 h). It is proposed that the formation of crosslinking structure of SA and introduction of MXene with good conductivity and high specific surface area contributed to the high performance of the composite FHS. Moreover, the FHS could promptly differentiate respiration status, recognize speech and measure fingertip movement, indicating potentials in breath monitoring and non-contact human-machine interactions. This work provides guidance for developing advanced flexible sensors with wide application scope in wearable electronics.

The wavelet spectral characteristics of three respiratory muscle signals (Scalenus (SC), Parasternal intercostal (IC) and Rectus abdominis (RA)) and one locomotor muscle Brachioradialis (BR) were analyzed in the time-frequency (T-F) domain during breath-holding (BH). Study was performed for an end-expiratory BH maneuver on twelve healthy, physically active, naive apneists (6 professional athletes; 6 recreational athletes, two in the post-COVID-19 period) using surface electromyography (sEMG). We observe individual effects dependent on muscle oxygenation and person’s fitness, consistent with the mechanism of motor unit (MU) recruitment and the transition of slow-twitch oxidative (type 1) to fast-twitch (oxidative) glycolytic (type 2) muscle fibers. Professional athletes had longer BH duration (BHD) and strong hypercapnic response on expiratory RA, which is activated abruptly at higher BHDs in a person-specific range below 250 Hz and dependent on BHD. This is in contrast with recreational athletes, who had strong hypoxic response on inspiratory IC, which is activated faster and gradually in the frequency range of 250-450 Hz (independent of the apneist and BHD). This pilot study preliminarily indicates that it is possible to non-invasively assess the physiological characteristics of skeletal muscles, especially oxygenation, and improve physical fitness tests by determining T-F features of elevated myoelectric IC and RA activity during BH.

Many individuals are wearing face masks improperly at ‘half mask’ and potentially breathing out microbes that can contaminate the air as well as anything below the nose. This note provides the first report that bacteria and fungi breathed out during nasal air exhalation are able to be cultured after landing on blood agar plates. The CFU’s are higher after both 10 breaths and extremely significant for 20 breaths compared to the control plates exposed to the air. Implications of this finding are that going ‘nose commando’ may be able to continue the spread of respiratory diseases such as COVID-19.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

We conducted many model simulations to understand the causes of the damages of coronavirus to lung tissues and constructed a diagram showing viral development, immune response and damage accumulation curves. We found that main causes are (1) the phase lag between the viral reproduction process and a belayed immune response, (2) the direct viral damages and massive collateral damages which are mainly caused by belated immune responses, and (3) further tissue damages triggered by accumulated wastes in lungs. We deduced from those causes that the key strategies for preventing lung damages include avoiding direct lung infection, altering host-virus interactions, promoting immune responses, diluting virus concentrations in lung tissues by promoting viral migration to the rest of the body, maintaining waste removal balance, protecting heart function and renal function, avoiding other infections, reducing allergic reactions and other inflammation, etc. We finally discussed how to use dietary, medical, emotional, lifestyle, environmental, mechanical factors, etc. to alter disease outcomes. We show why true benefits of those factors cannot be determined by randomized controlled trials, and why the multiple-factor optimization approach can be highly effective by examining organ usable capacity in the cause of death. This treatment protocol using water, air, salt, sound, temperature, emotion, exercise, etc. can be the most powerful cures for viral and non-viral lung infections because they do not depend on molecular specificity and are freely available to anyone.

The reliable online analysis of volatile compounds in exhaled breath remains a challenge as a plethora of molecules occur in different concentration ranges (i.e. ppt to %), and need to be detected against an extremely complex background matrix. While this complexity is commonly addressed by hyphenating a specific analytical technique with appropriate preconcentration and/or preseparation strategies prior to detection, we herein propose the combination of three analytical tools based on truly orthogonal measurement principles as an alternative solution: field-asymmetric ion mobility spectrometry (FAIMS), Fourier-transform infrared (FTIR) spectroscopy-based sensors utilizing substrate-integrated hollow waveguides (iHWG), and luminescence sensing (LS). These three tools have been integrated into a single compact analytical platform suitable for online exhaled breath analysis. The analytical performance of this prototype system was tested via artificial breath samples containing nitrogen (N2), oxygen (O2), carbon dioxide (CO2) and acetone as a model volatile organic compound (VOC) commonly present and detected in breath. Functionality of the combined system was demonstrated by detecting these analytes in their respectively breath-relevant concentration range and mutually independent of each other generating orthogonal yet correlated analytical signals. Finally, adaptation of the system towards the analysis of real breath samples during future studies is discussed.