Human Exhaled Air Research Articles

Towards detection of cancer biomarkers in human exhaled air by transfer-learning-powered analysis of odor-evoked calcium activity in rat olfactory bulb

Detection of volatile organic compounds in exhaled air is a promising approach to non-invasive and scalable gastric cancer screening. This work proposes a new approach for the detection of volatile organic compounds by analyzing odor-evoked calcium responses in the rat olfactory bulb. We estimate the feasibility of gastric cancer biomarker detection added to the exhaled air of healthy participants. Our detector consists of a convolutional encoder and a similarity-based classifier over encoder outputs. To minimize overfitting on a small available training set, we involve a pre-training where the encoder is trained on synthetic data representing spatiotemporal patterns similar to real calcium responses in the olfactory bulb. We estimate the classification accuracy of exhaled air samples by matching their encodings with encodings of calibration samples of two classes: 1) exhaled air and 2) a mixture of exhaled air with the cancer biomarker. On our data, the accuracy increased from 0.68 on real data up to 0.74 if pre-training on synthetic data is involved. Our work is focused on proving the feasibility of proposed new approach rather than on comparing its efficiency with existing methods. Such detection is often performed with an electronic nose, but its output becomes unstable over time due to a sensor drift. In contrast to the electronic nose, rats can robustly detect low concentrations of biomarkers over lifetime. The feasibility of gastric cancer biomarker detection in exhaled air by bio-hybrid system is shown. Pre-training of neural models for images analysis increases the accuracy of detection.

Volatomics in healthcare: technical basis and clinical application

Volatilome is a collection of all volatile compounds, both organic and inorganic, the source of which is the object under study. Unlike the metabolome, which includes only compounds of endogenous origin, the concept of volatilome includes substances of both endogenous and exogenous origin. Exhaled air volatilome contains thousands of metabolites and volatile organic compounds (VOCs), which are formed both in the respiratory tract and in the systems of internal organs and tissues. The study of the chemical composition of human exhalation can provide clinically useful information about the state of human health, while the studies are non-invasive and safe for the patient. The instrumental methods used in the study of human volatilome make it possible to online examine large numbers of patients. All this contributes to a high interest on the part of the medical community in the study of human exhaled air volatilome and suggests that the methods of these research methods have a high potential for implementation in clinical practice.

Human exhaled air diagnostic markers for respiratory tract infections in subjects receiving mechanical ventilation

Diagnosing respiratory tract infections (RTIs) in critical care settings is essential for appropriate antibiotic treatment and lowering mortality. The current diagnostic method, which primarily relies on clinical symptoms, lacks sensitivity and specificity, resulting in incorrect or delayed diagnoses, putting patients at a heightened risk. In this study we developed a noninvasive diagnosis method based on collecting non-volatile compounds in human exhaled air. We hypothesized that non-volatile compound profiles could be effectively used for bacterial RTI diagnosis. Exhaled air samples were collected from subjects receiving mechanical ventilation diagnosed with or without bacterial RTI in intensive care units at the Johns Hopkins Hospital. Truncated proteoforms, a class of non-volatile compounds, were characterized by top-down proteomics, and significant features associated with RTI were identified using feature selection algorithms. The results showed that three truncated proteoforms, collagen type VI alpha three chain protein, matrix metalloproteinase-9, and putative homeodomain transcription factor II were independently associated with RTI with the p-values of 2.0 × 10−5, 1.1 × 10−4, and 1.7 × 10−3, respectively, using multiple logistic regression. Furthermore, a score system named ‘TrunScore’ was constructed by combining the three truncated proteoforms, and the diagnostic accuracy was significantly improved compared to that of individual truncated proteoforms, with an area under the receiver operator characteristic curve of 96.9%. This study supports the ability of this noninvasive breath analysis method to provide an accurate diagnosis for RTIs in subjects receiving mechanical ventilation. The results of this study open the doors to be able to potentially diagnose a broad range of diseases using this non-volatile breath analysis technique.

Isoprene and its Overall Impacts: Review

A clean environment is a suitable medium for providing requirements that sustain the organisms living therein. Hence, it is a ‘natural-store house’ to receive and provide the metabolic needs of the biotic and abiotic systems. It also accomplishes the crucial geochemical cycles that maintain their appropriate balance. The metabolites may be quantitatively and qualitatively meagre but cause good and bad impacts. The organisms also contribute to these metabolites. The anthropogenic interference a prime causes of environmental disturbances and renders the environment unsuitable. Isoprene is one of the biogenic and abiogenic volatile organic compounds prominently present in the lower troposphere. Normally, this volatile compound interacts with ozone, hydroxyl and oxides of nitrogen and causes depletion of ozone. Trees that combat unfavorable fluctuations in environmental parameters like high winds, tornadoes, extreme temperature, drought (a complex impact), flood, wild fires, and deficiency of nutrition, experience the influence of isoprene. Mostly the developing countries encounter poor air quality that contains particulate matter, pollutants resulting in respiratory illness, cardiovascular and cancerous ailments. The presence of volatile organic components in human exhaled air indicates their metabolic or the ambient environmental origin. The endogenous organic volatile compounds present in human breath are the biomarkers for the pathophysiological conditions and are of clinical and biomedical significance, specifically during non-invasive estimations. Although, isoprene has attracted researchers but its pathophysiological impacts need more investigations, hence, this presentation to evaluate the effects of isoprene in biosphere.

Разработка технологии исследования легочной сурфактантной системы с помощью электрической генерации капиллярных волн (экспресс метод)

Based on the use of a new design of a capillary wave generator, a method is proposed for studying the human surfactant system for diagnosing patients suffering from pulmonary diseases, including after infection with COVID-19. The study of the surfactant system of the lungs (SSL) in a healthy organism and in pathology is one of the important tasks of modern pulmonology. The proposed method for monitoring human exhaled air condensate consists in applying a condensate sample to the surface of an aqueous solution, on which capillary waves are created due to the phenomenon of electrostriction, the change in the amplitude and phase of which makes it possible to determine the surface tension of the liquid and the parameters of the surfactant layer. To this end, we have developed a design and received a patent for the invention of a liquid parameter meter containing a liquid cuvette, a generator associated with a system for creating capillary waves on the liquid surface and a system for recording the characteristics of liquid vibrations. Improving the technology of the CCL control process is aimed at solving the problems of reducing the time of measuring the CCL and reducing the cost of the method.

Respirometry Rate Measurement by Pyroelectric Effect of a Piezo Sounder—Monitor and Alarm by Single Device

This article describes a novel application of a piezoelectric sounder on an acoustic device as a respiratory detector. When human exhaled air at a temperature of 36.5 °C is blown onto the piezoelectric device in the sounder in a room of 26.4 °C, a peak voltage of 1–2 V directly appears without an amplifier. We herein present a theoretical model of how the device works, experimentally prove its validity, and show its potential to be used as a spirometry detector. The output voltage changes alongside the output of a medical spirometer for forced vital capacity test respiration. The device is noise robust under a variety of measurement conditions, including different masks, shields, snorkels, and sustained airway positive pressure devices. The S/N ratios for quiet sitting, walking, quick face swing, and mask movement were 38, 33.3, 32.3, and 30.9 dB, respectively. The piezoelectric sounder considered herein can return to the original function and generate an alarm if the measured reparation is abnormal.

Numerical methods of spectral analysis of multicomponent gas mixtures and human exhaled breath

In this paper, the application of machine learning and deep learning in the spectral analysis of multicomponent gas mixtures is considered. The experimental setup consists of a quantum cascade laser with a tuning range of 5.3–12.8 µm, a peak power of up to 150 mW, and an astigmatic Herriott gas cell with an optical path length of up to 76 m. Acetone, ethanol, methanol, and their mixtures are used as test substances. For the detection and clustering of substances, including molecular biomarkers, methods of machine learning, such as stochastic embedding of neighbors with a t-distribution, principal component analysis and classification methods, such as random forest, gradient boosting, and logistic regression, are proposed. A shallow convolutional neural network based on TensorFlow (Google) and Keras is used for the spectral analysis of gas mixtures. Model spectra of substances are used as a training sample, and model and experimental spectra are used as a test sample. It is shown that neural networks trained on model spectra (NIST database) can recognize substances in experimental gas mixtures. We propose using machine learning methods for clustering and classification of pure substances and gas mixtures and neural networks for the identification of gas mixture components. Using the experimental setup described, the experimentally obtained concentration limits are 80 ppb for acetone and 100–120 ppb for ethanol and methanol. The possibility of using the proposed methods for analyzing spectra of human exhaled air is shown, which is significant for biomedical applications.

Formulation of Chlorine-Dioxide-Releasing Nanofibers for Disinfection in Humid and CO2-Rich Environment.

Background: Preventing infectious diseases has become particularly relevant in the past few years. Therefore, antiseptics that are harmless and insusceptible to microbial resistance mechanisms are desired in medicine and public health. In our recent work, a poly(ethylene oxide)-based nanofibrous mat loaded with sodium chlorite was formulated. Methods: We tested the chlorine dioxide production and bacterial inactivation of the fibers in a medium, modeling the parameters of human exhaled air (ca. 5% (v/v) CO2, T = 37 °C, RH > 95%). The morphology and microstructure of the fibers were investigated via scanning electron microscopy and infrared spectroscopy. Results: Smooth-surfaced, nanoscale fibers were produced. The ClO2-producing ability of the fibers decreased from 65.8 ppm/mg to 4.8 ppm/mg with the increase of the sample weight from 1 to 30 mg. The effect of CO2 concentration and exposure time was also evaluated. The antibacterial activity of the fibers was tested in a 24 h experiment. The sodium-chlorite-loaded fibers showed substantial antibacterial activity. Conclusions: Chlorine dioxide was liberated into the gas phase in the presence of CO2 and water vapor, eliminating the bacteria. Sodium-chlorite-loaded nanofibers can be sources of prolonged chlorine dioxide production and subsequent pathogen inactivation in a CO2-rich and humid environment. Based on the results, further evaluation of the possible application of the formulation in face-mask filters as medical devices is encouraged.

Масс-спектрометрические исследования состава газовыделения живых организмов

The quantitative and qualitative composition of volatile organic compounds (VOCs) of human exhaled air, the air environment of various types of entomopathogenic fungi (EPF) of the genus Lecanicillium, used as an alternative to chemical pesticides to protect plants from pests, cabbage moth caterpillars, as well as spined soldier bug from the shield family, was studied using a quadrupole mass spectrometer. The main components found were acetone, acetic acid, and isoprene. These components in human exhalation are significant indicators for non-invasive disease diagnosis. For the first time, sulfur dioxide was found in the composition of VOC EPF, as one of the possible repellents. The caterpillars of cabbage moth secrete exclusively acetic acid.

Mass spectrometric gas release composition studies of living organisms

The quantitative and qualitative composition of volatile organic compounds (VOCs) of human exhaled air, the air environment of various types of entomopathogenic fungi (EPF) of the genus Lecanicillium, used as an alternative to chemical pesticides to protect plants from pests, cabbage moth caterpillars, as well as spined soldier bug from the shield family, was studied using a quadrupole mass spectrometer. The main components found were acetone, acetic acid, and isoprene. These components in human exhalation are significant indicators for non-invasive disease diagnosis. For the first time, sulfur dioxide was found in the composition of VOC EPF, as one of the possible repellents. The caterpillars of cabbage moth secrete exclusively acetic acid. Keywords: mass spectrometry, volatile organic compounds analysis, exhaled air, entomopathogenic fungi, Mamestra brassicae L., Podisus maculiventris S.

Influence of Human Behavior on Indoor Air Quality in a Care Facility for the Elderly in Japan

Volatile organic compounds (VOCs), CO2, temperature, and humidity in a private room in a care facility for the elderly were measured and the behavior of a resident and staff were recorded in order to clarify the effects of the resident’s behavior, especially defecation, on indoor air quality. Average indoor concentrations of total VOCs (in μg m−3) in summer, autumn, and winter were 40.9, 16.7, and 18.8, respectively. Average indoor concentrations of CO2 in summer, autumn, and winter were 813, 761, and 1144 ppm, respectively, revealing a tendency for the concentrations of CO2 to be higher in winter, in contrast to the VOC concentration. The concentrations of VOCs and CO2 were 1.1 to 1.5 times higher when the resident was present in the room than when the resident was absent. This result suggests that one of the main sources of VOC and CO2 emissions in indoor air was the resident. Acetic acid, 1-butanol, propanoic acid, hexanoic acid, and phenol, which are contained in human sweat, exhaled air, and excrement, were the predominant VOCs in the air of the room regardless of the season, and these five components accounted for more than 90% of the total VOCs. The concentrations of these components were higher when the resident was present in the room, suggesting that the resident was the main source of these components. Based on the changes in the VOC and CO2 concentrations over time and the records of the resident and the staff, it was noted that VOC concentrations decreased, in some cases, before and after diaper changes. Our research suggests that certain aspects of the behavior of residents can be inferred by monitoring changes in indoor air quality.

Selective Recognition of Acetone in Air Against Hydrogen By Impedance Measurement of Two-Terminal Electrochemical Sensors Based on Ionic Liquids

Introduction Ionic Liquids (ILs) are molten salts at room temperature and have both solvent and electrolyte properties. ILs have been actively studied for use in electrochemical gas sensors, thanks to their gas absorption property, electrochemical stability, and low evaporation loss. For example, gas sensors based on the changes in electrical double layer capacitance or in bulk impedance induced by gas dissolution in ionic liquids have been reported [1, 2]. However, there are few reports on the selective recognition of volatile organic compounds such as metabolites in human exhaled air against interfering gases. In this study, we demonstrated selective recognitions of acetone, which is a typical low-molecular-weight metabolic gas in human exhaled air, against hydrogen, which is a metabolite of enterobacteria, by electrochemical impedance measurement using ionic liquids. Method The interdigitated electrodes made of Cr/Pt shown in Fig. 1 were fabricated on a glass substrate. The 3-nm-thick chromium film acting as the adhesion layer was deposited by electron beam evaporation technique, which was followed by the pattern definition and evaporation of 100-nm-thick platinum electrode acting as the main electrical conduction layer. The droplet of 3-μL 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, a kind of ionic liquids, was casted onto the electrodes, which completed the fabrication of a two-terminal electrochemical sensor. The impedance measurements were performed under various atmospheres. The following shows the sequence of atmospheres under which the impedance responses of the fabricated sensors were measured. ⅰ) Dry air (3 min) ⅱ) (case Ⅰ) 25-ppm H2 in dry air (3 min)ⅱ) (case Ⅱ) 25-ppm CH3COCH3 in dry air (3 min) ⅲ) dry air (3 min)In the second process ii), case I or case II was chosen from two target gases; hydrogen and acetone. The gas flow rate was kept constant at 200 sccm. Impedance measurements were performed using an LCR meter (Keysight E4980A) with DC bias of 0.0 V and AC amplitude of 10 mV. The measurement frequency was varied from 300 kHz to 20 Hz. Results Fig. 2 shows the measured sensor response at (a) 200 kHz, (b) 30 Hz, and (c) 350 Hz. The sensor response is defined as impedance change ΔZ re due to target molecules normalized by the impedance in dry air Z re(Air), where Z re represents the real part of the impedance. The equation used to extract the sensor response is shown in Fig. 2. We noticed that the sensor response was strongly dependent on the measured frequency. Z re decreases at 200 kHz in both the CH3COCH3 and H2 atmospheres (Fig. 2(a)), whereas it is increased by the target molecules at 30 Hz (Fig. 2(b)). The directions of the impedance changes were the same for both the target molecules. On the other hand, at 350 Hz (Fig. 2(c)), Z re decreases in the CH3COCH3 atmosphere, although it stays constant in the H2 atmosphere. This clearly demonstrates that CH3COCH3 can be selectively detected against H2 by impedance measurement with an appropriate measurement frequency. Discussion and Conclusion We consider that the equivalent circuit of the present system includes an element related with the bulk IL resistance and one related with the electrical double layer at the electrode/IL interfaces. The measurement of the impedance phase angle reveals that the phase angle is close to 0 degrees at 200 kHz and close to -90 degrees at 30 Hz. Therefore, we consider that high-frequency (200 kHz) Z re is affected by the bulk IL resistance change induced by dissolved gaseous molecules and that low-frequency (30 Hz) Z re is influenced by the change in electrical double layer characteristics. On the other hand, at medium frequencies; namely 350 Hz in this study, the gas-induced effects both on bulk IL resistance and on the electric double layer characteristics causing Z re modulation may be compensated with each other, and no sensor response was observed under the H2 atmosphere as shown in Fig. 2(c). We will extract the equivalent circuit model for the system used in this experiment and examine how the parameters of circuit elements change in the H2 and CH3COCH3 atmospheres in comparison with the standard dry air atmosphere. By investigating the frequency dependence of the impact of each parameter change on Z re, we will clarify the mechanism of Z re constancy in the H2 atmosphere at medium frequencies.

Humidity Sensor Based on PEO/PEDOT:PSS Blends for Breath Monitoring

AbstractThe discrimination of humidity in exhaled breath is of utmost importance to turn breath analysis into an efficient noninvasive tool for early diagnosis or treatment monitoring of several diseases. Herein, by assembling different ratios of the conductive poly(3,4‐ethylenedioxythiophene): polystyrene sulfonate with the polymer matrix polyethylene oxide (PEO), humidity chemiresistor‐based sensors are designed and investigated. The testing results display a broad relative humidity detection range (6–92%), repeatability, reproducibility, and good reversibility. Meanwhile, the sensors possess good reliability for distinct temperatures and in the presence of typical volatile organic compounds found in human exhaled air. The hygroscopic idiosyncrasy of PEO is attributed to be the main responsible for the high sensibility toward humidity. In a proof‐of‐principle for detection of respiration humidity, the outcome shows the ability of the chemiresistors to detect the humidity variation in a real case of breath exposure up to 2 s intervals. The 30 d trial of stability readings shows a standard deviation of only 2.6%. These sensing devices appear as a new array component able to distinguish moisture from biomarkers of diagnosed diseases in breath analysis.

Experimental Setup Based on a Quantum Cascade Laser Tunable in the Wavelength Range of 5.3–12.8 µm for Spectral Analysis of Human Exhaled Air

Experimental Setup Based on a Quantum Cascade Laser Tunable in the Wavelength Range of 5.3–12.8 µm for Spectral Analysis of Human Exhaled Air

Isotopic gas analysis by means of mid-infrared photoacoustic spectroscopy targeting human exhaled air.

There is a great need for cost-efficient non-invasive medical diagnostic tools for analyzing humanly exhaled air. Compared to present day methods, photoacoustic spectroscopy (PAS) can provide a compact and portable (bedside), sensitive and inexpensive solution. We demonstrate a novel portable photoacoustic spectroscopic platform for isotopic measurements of methane (CH4). We identify and discriminate the 12CH4- and 13CH4 isotopologues and determine their mixing ratio. An Allan deviation analysis shows that the noise equivalent concentration for CH4 is 200 ppt (pmol/mol) at 100 s of integration time, corresponding to a normalized noise equivalent absorption coefficient of 5.1×10-9Wcm-1Hz-1/2, potentially making the PAS sensor a truly disruptive instrument for bedside monitoring using isotope tracers by providing real-time metabolism data to clinical personnel.

Экспериментальная установка на базе перестраиваемого в диапазоне волн 5.3-12.8 μm квантово-каскадного лазера для спектрального анализа выдыхаемого человеком воздуха

An experimental setup and a method for analyzing multicomponent gas mixtures, including human exhaled air, are presented. The installation consists of a quantum cascade laser, tunable in the wavelength range of 5.3-12.8 µm, with a peak power of 150 mW, and a multi-pass Herriot gas cell, which allows obtaining an optical path of up to 76 m. The registration time of a single spectrum is about 50 ms. For acetone and ethanol, which are potential biomarkers of some human diseases, the sensitivity threshold at the sub-ppm level was experimentally determined. A system of sample preparation and pre-drying is proposed, which allows analyzing both multicomponent gas mixtures and the air exhaled by a person. The variants of application of the described installation in biomedical applications are proposed.

SARS-CoV-2 Rapid Detection System using Electric Current-Spectrum for Human Exhaled Air Samples

The SARS-COV-2 Rapid Detection System is a SARS-COV-2 Electro-Spectroscopy detection system. The preliminary design of this system was studied theoretically in this paper. This system can detect the existence of sub-micro impurity particles in the human exhaled air, based on the unique shape, dimensions and density of these sub-micro impurities, such as viral particles, including CORONA viruses. This information is carried out by electron current buildup forming Electric Current-Spectrum (ECS) distinguishing the contents of the exhaled air. The design is based on Flashing Ratchet Potential (FRP) and beam of free electrons passing through the electrodes of the FRP. The ECS is characterized by curve deviations caused by interaction of low energy electrons’ (-β radiation) with matter, which depends on the matter’s shape, dimension and density. This interaction causes a scattering (delaying) or absorption of the electrons by matter, by elastic or inelastic collisions, respectively. The ability of FRP to drift back the delayed electrons to their initial points can be used to characterize the produced ECS. The effect of delayed electrons can be amplified to form a visualized deviation in the ECS by electron multiplication system and can be interpreted into distinguishable SARS-COV-2 Barcodes or Fingerprints.

Rapid Detection of Femtogram Amounts of Protein by Gel-Free Immunoblot.

The article presents a new method of immunoblotting for simple, rapid, and highly sensitive detection of proteins. Electrophoretic separation of sample is carried out under non-denaturing conditions in a thin conductive layer between cellulose membranes without polyacrylamide gel. The membrane surface is preliminarily modified with azidophenyl groups to photochemically immobilize proteins in situ. For visualization of protein bands, the membranes are treated with magnetic beads coated with specific antibodies, unbound particles are then removed with a magnet. The detection limit in the model system with biotinylated BSA and magnetic beads coated with streptavidin reaches 10 fg or about 105 molecules, while the total blotting time does not exceed 5 min. The method was applied for detection of IgA in a sample of human exhaled air. The method can be used for the analysis of various complex biological samples containing low amounts of the analyte.

All-Painting Process To Produce Respiration Sensor Using Humidity-Sensitive Nanoparticle Film and Graphite Trace

We propose an all-painting process to produce a respiration sensor made from a humidity-sensitive nanoparticle (NP) film and a graphite trace. The sensor is fabricated under ambient air with a simple vacuum-free process for green electronics: solely hand-painting on a cellulose acetate film. A humidity-sensitive silica NP film is painted by brush on pencil-trace graphite electrodes. An all-painted humidity sensor using this film shows 106% sensitivity within a 10–93% humidity change. The film is flexible and the humidity sensor operates as a respiration sensor after bending test. We design an all-painted respiration sensor using the humidity sensor and a painted resistor. Finally, we integrate the all-painted respiration sensor, a flexible temperature sensor, and a portable data logger as a portable bifunctional health-care device. The device on a mask can monitor human respiration rate and exhaled air temperature simultaneously.

Human exhaled air can efficiently support in vitro maturation of porcine oocytes and subsequent early embryonic development.

Air phase is an indispensable environmental factor affecting oocyte maturation and early embryo development. Human exhaled air was previously proved to be a reliable and inexpensive atmosphere that sustains normal early development of mouse and bovine embryos. However, whether human exhaled air can support in vitro maturation (IVM) of porcine oocytes is not yet known. To evaluate the feasibility of maturing oocytes in human exhaled air, we examined oocyte morphology, BMP15 expression, nuclear and cytoplasmic maturation. We found that cumulus expansion status, expression levels of BMP15 important for cumulus expansion and the rate of first polar body emission were similar among human exhaled air, 5% O2 or 20% O2 in air after IVM of 44 h. Furthermore, the percentage of metaphase II (MII) oocytes showing normal cortical and sub-membranous localization of cortical granules and diffused mitochondrial distribution patterns is comparable among groups. The cleavage, blastocyst rate and total cell number were not apparently different for parthenogenetic activated and somatic cloned embryos derived from MII oocytes matured in three air phases, suggesting oocytes matured in human exhaled air obtain normal developmental competence. Taken together, human exhaled air can efficiently support in vitro maturation of porcine oocytes and subsequent early embryonic development.