Compounds In Human Breath Research Articles

Gas chromatography-ion mobility spectrometry for the detection of human disease: a review.

Gas chromatography-ion mobility spectrometry (GC-IMS) is an advanced technique used for detecting trace compounds, due to its non-destructive, straightforward, and rapid analytical capabilities. However, the application of GC-IMS in human disease screening is barely reported. This review summarizes the application and related parameters of GC-IMS in human disease diagnosis. GC-IMS detects volatile organic compounds in human breath, feces, urine, bile, etc. It can be applied to diagnose diseases, such as respiratory diseases, cancer, enteropathy, Alzheimer's disease, bacterial infection, and metabolic diseases. Several potential disease markers have been identified by GC-IMS, including ethanal (COVID-19), 2-heptanone (lung cancer) and 3-pentanone (pulmonary cryptococcosis). In conclusion, GC-IMS offers a non-invasive approach to monitor and diagnose human diseases with broad applications.

Volatile Organic Compounds in Human Breath.

A comprehensive analysis of volatile organic compounds (VOCs) from the exhaled breath sample is termed as breathomics. Breath samples are a complex mixture composed of a multitude of VOCs and other molecules. The analysis of total VOCs in exhaled breath provides a promising tool for the diagnosis of many diseases because it enables the observation of biochemical processes in the body in a non-invasive way. VOCs are produced in various physiological and pathophysiological conditions thus making it a potential biomarker for several diseases.

Selected ion flow tube mass spectrometry for targeted analysis of volatile organic compounds in human breath.

The analysis of volatile organic compounds (VOCs) within breath for noninvasive disease detection and monitoring is an emergent research field that has the potential to reshape current clinical practice. However, adoption of breath testing has been limited by a lack of standardization. This protocol provides a comprehensive workflow for online and offline breath analysis using selected ion flow tube mass spectrometry (SIFT-MS). Following the suggested protocol, 50 human breath samples can be analyzed and interpreted in <3 h. Key advantages of SIFT-MS are exploited, including the acquisition of real-time results and direct compound quantification without need for calibration curves. The protocol includes details of methods developed for targeted analysis of disease-specific VOCs, specifically short-chain fatty acids, aldehydes, phenols, alcohols and alkanes. A procedure to make custom breath collection bags is also described. This standardized protocol for VOC analysis using SIFT-MS is intended to provide a basis for wider application and the use of breath analysis in clinical studies.

A flexible virtual sensor array based on laser-induced graphene and MXene for detecting volatile organic compounds in human breath.

Detecting volatile organic compounds (VOCs) in human breath is critical for the early diagnosis of diseases. Good selectivity of VOC sensors is crucial for the accurate analysis of VOC biomarkers in human breath, which consists of more than 200 types of VOCs. In this paper, a flexible virtual sensor array (FVSA) was proposed based on a sensing layer of MXene and laser-induced graphene interdigital electrodes (LIG-IDEs) for detecting VOCs in exhaled human breath. The fabrication of LIG-IDEs avoids the costly and complicated procedures required for the preparation of traditional IDEs. The FVSA's responses of multiple parameters help build a unique fingerprint for each VOC, without a need for changing the temperature of the sensing element, which is commonly used in the VSA of semiconductor VOC sensors. Based on machine learning algorithms, we have achieved highly precise recognition of different VOCs and mixtures and accurate prediction (accuracy of 89.1%) of the objective VOC's concentration in variable backgrounds using this proposed FVSA. Moreover, a blind analysis validates the capacity of the FVSA to identify alcohol content in human breath with an accuracy of 88.9% using breath samples from volunteers before and after alcohol consumption. These results show that the proposed FVSA is promising for the detection of VOC biomarkers in human exhaled breath and early diagnosis of diseases.

On-line Detection of Volatile Sulfur Compounds in Breath Gas by Proton Transfer Reaction Mass Spectrometry†

To develop a kind of noninvasive method of breath diagnosis in diseases,much attention has been paid to the study of the relation between diseases and volatile organic compounds in human breath gas.However,the gas in oral cavity was usually ignored in many studies of breath gas. The bad breath odor of a participant was studied by a home-made proton transfer reaction mass spectrometer( PTR-MS). The breath via the mouth,breath via the nose and the air in the mouth cavity were monitored with the mode of multiple ion detect scans. The results show that three different volatile sulfur compounds that cause bad breath odor should be attributed to different sources. The source of methyl mercaptan in breath is oral cavity,and the source of hydrogen sulphide and dimethylsulfide in breath is lung or respiratory tract. The related result is very important to sampling and detection of breath gas.

Breath and Air Analysis: Applications in Resource-poor Settings

Recent research developments have led to the emergence of various portable and affordable gaseous-compound detecting devices. These non-invasive technologies detect volatile organic compounds in human breath or air, providing important information about us and our environment. While many of these technologies have been seamlessly integrated into Western countries, they have yet to be leveraged in developing nations. These devices can be used to easily and affordably screen patients for diabetes, monitor air quality of cities, and facilitate agricultural intensification. This article describes five scenarios where breath and air analysis technologies can address problems faced by populations in resource-poor settings.

Review article: breath analysis in inflammatory bowel diseases.

There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10(-7)) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1β showed an inverse relation with clinical disease activity. Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.

Real-time multi-marker measurement of organic compounds in human breath: towards fingerprinting breath

The prospects for exploiting proton transfer reaction-time of flight-mass spectrometry (PTR-ToF-MS) in medical diagnostics are illustrated through a series of case studies. Measurements of acetone levels in the breath of 68 healthy people are presented along with a longitudinal study of a single person over a period of 1 month. The median acetone concentration across the population was 484 ppbV with a geometric standard deviation (GSD) of 1.6, whilst the average GSD during the single subject longtitudinal study was 1.5. An additional case study is presented which highlights the potential of PTR-ToF-MS in pharmacokinetic studies, based upon the analysis of online breath samples of a person following the consumption of ethanol. PTR-ToF-MS comes into its own when information across a wide mass range is required, particularly when such information must be gathered in a short time during a breathing cycle. To illustrate this property, multicomponent breath analysis in a small study of cystic fibrosis patients is detailed, which provides tentative evidence that online PTR-ToF-MS analysis of tidal breath can distinguish between active infection and non-infected patients.

The effect of a paced auditory serial addition test (PASAT) intervention on the profile of volatile organic compounds in human breath: a pilot study

This study sought to identify if detectable changes in human breath profiles may be observed following a psychological intervention designed to induce stress, a paced auditory serial addition test (PASAT). Breath samples were collected from 22 participants (10 male and 12 female) following a double cross-over randomized design with two experimental interventions. One intervention required participants to listen to classical music chosen to be neutral. The other intervention required participants to undertake a PASAT that induced cardiovascular responses consistent with acute stress. Both interventions also involved two sequences of cognitive function tests. Blood-pressure and heart-rate were recorded throughout each intervention and distal breath samples were collected onto Tenax® TA/Carbograph 1 thermal desorption tubes, using an adaptive breath sampler. Samples were collected before and after the PASAT. Breath samples were analysed by thermal desorption gas chromatography-mass spectrometry. Data registration using retention indexing and peak deconvolution followed by partial least-squares discriminant analysis identified six stress sensitive compounds. A principal components analysis model based on these components generated a model that predicted post-PASAT versus post-neutral intervention samples with a sensitivity of 83.3% and a selectivity of 91.6% for females, compared to 100% sensitivity and 90% selectivity for males. Of the six compounds indole, 2-hydroxy-1-phenylethanone, benzaldehyde, and 2-ethylhexan-1-ol were identified on the basis of mass spectral, retention indexing and confirmation against pure standards. 2-methylpentadecane was tentatively identified from mass spectral and retention indexing, whilst one component has yet to be assigned, although the mass spectrum is indicative of a terpene. Indole and 2-methylpentadecane concentrations increased in response to the PASAT intervention, while the other compounds reduced in their abundance in human breath, possibly as a result of ventilation effects.

Applications of a confined DART (direct analysis in real time) ion source for online in vivo analysis of human breath

Human breath is composed of many volatile metabolites that can potentially provide information about a person's health status. A sensitive assay to identify these volatile organic compounds as biomarkers is ideal and important for early detection of many diseases. However, the diagnosis through online breath analysis based on mass spectrometry is difficult due to the low concentration of pertinent compounds in breath. The DART (direct analysis in real time) ion source is a novel atmospheric pressure ionization technique, which can efficiently ionize gaseous, liquid and solid samples with high throughput. A major problem in analysis of gaseous samples is its poor detection sensitivity due to open-air sampling. Recently, a confined DART ion source (cDART) was developed, where the plasma generated by the atmospheric pressure glow discharge ionizes gas-phase molecules in a Tee-shaped flow tube instead of open air. It leads to a significant increase of the ionization efficiency of gaseous samples. In this study, the cDART source was modified and applied in online analysis of exhaled breath. The limit of detection of the improved cDART source was determined to be at the level of low ppb. The cDART source was used in the real-time monitoring of an oral anesthetic drug. The concentration variations of two active ingredients in exhaled breath, menthol and benzocaine, and their metabolites with time were obtained. The results show that the cDART ion source is a powerful analytical tool to provide high sensitivity and high throughput analysis for volatile organic compounds in human breath, and can find potential applications in clinical diagnosis and therapy.

Determination of Volatile Organic Compounds in Human Breath by Optical Fiber Sensing

Determination of Volatile Organic Compounds in Human Breath by Optical Fiber Sensing

Identification of volatile lung cancer markers by gas chromatography–mass spectrometry: comparison with discrimination by canines

In this work, a chromatographic method for identification of volatile organic compounds was compared with canine recognition. Gas chromatography and mass spectrometry (GC–TOF MS) were used for determination of concentrations of trace gases present in human breath. The technique enables rapid determination of compounds in human breath, at the parts per billion level. Linear correlations were from 0.83–234.05 ppb, the limit of detection was the range 0.31–0.75 ppb, and precision, expressed as relative standard deviation (RSD), was less than 10.00 %. Moreover, trained dogs are able to discriminate breath samples of patients with diagnosed cancer. We found a positive correlation between dog indications and the ethyl acetate and 2-pentanone content of breath (r = 0.85 and r = 0.97, respectively). The methods presented for detection of lung cancer markers in exhaled air could be used as a potential non-invasive tool for screening. In addition, the canine method is relatively simple and inexpensive in comparison with chromatography.

Sparse representation-based classification for breath sample identification

It has been discovered that some compounds in human breath can be used to detect some diseases and monitor the development of the conditions. A sensor system in tandem with certain data evaluation algorithm offers an approach to analyze the compositions of breath. Currently, most algorithms rely on the generally designed pattern recognition techniques rather than considering the specific characteristics of data. They may not be suitable for odor signal identification. This paper proposes a Sparse Representation-based Classification (SRC) method for breath sample identification. The sparse representation expresses an input signal as the linear combination of a small number of the training signals, which are from the same category as the input signal. The selection of a proper set of training signals in representation, therefore, gives us useful cues for classification. Two experiments were conducted to evaluate the proposed method. The first one was to distinguish diabetes samples from healthy ones. The second one aimed to classify these diseased samples into different groups, each standing for one blood glucose level. To illustrate the robustness of this method, two different feature sets, namely, geometry features and principle components were employed. Experimental results show that the proposed SRC outperforms other common methods, such as K Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), Artificial Neural Network (ANN), and Support Vector Machine (SVM), irrespective of the features selected.

Analysis of 2‐propanol in exhaled breath using in situ enrichment and cataluminescence detection

We report a simple gaseous sensor for the sensitive detection of trace 2-propanol in exhaled breath using in situ enrichment and cataluminescence detection method on the surface of nanomaterials. The influences of heating voltage and absorption time on the CTL intensity were discussed, respectively. In the selected conditions, the linear range of 2-propanol concentration is 60-600 ppbv and the detection of limit is 11 ppbv. Moreover, the lifetime and selectivity of the sensor were also investigated. It has the potential to diagnostic volatile organic compounds in human breath.

Determination of volatile organic compounds in human breath for Helicobacter pylori detection by SPME‐GC/MS

Helicobacter pylori living in the human stomach release volatile organic compounds (VOCs) that can be detected in expired air. The aim of the study was the application of breath analysis for bacteria detection. It was accomplished by determination of VOCs characteristic for patients with H. pylori and the analysis of gases released by bacteria in suspension. Solid-phase microextraction was applied as a selective technique for preconcentration and isolation of analytes. Gas chromatography coupled with mass spectrometry was used for the separation and identification of volatile analytes in breath samples and bacterial headspace. For data calculation and processing, discriminant and factor analyses were used. Endogenous substances such as isobutane, 2-butanone and ethyl acetate were detected in the breath of persons with H. pylori in the stomach and in the gaseous mixture released by the bacteria strain but they were not identified in the breath of healthy volunteers. The canonical analysis of discrimination functions showed a strong difference between the three examined groups. Knowledge of substances emitted by H. pylori with the application of an optimized breath analysis method might become a very useful tool for noninvasive detection of this bacterium.

Application of Femtosecond Laser Mass Spectrometry to the Analysis of Volatile Organic Compounds

Femtosecond (fs) lasers have high intensity and ultrashort pulse duration. Tunneling ionization occurs for molecules subject to such intense laser fields. We have studied the mass spectra of a variety of molecules irradiated by intense fs laser pulses. These molecules include some typical volatile organic compounds contained in human breath and in the atmosphere. The results demonstrate that all of these molecules can be ionized by intense fs laser pulses. Dominant parent ion and some characteristic ionic fragments are observed for each molecule. The degree of fragmentation can be controlled by adjusting the laser intensity. Moreover, saturation ionization can occur for each molecule by increasing the laser intensity. These features indicate that fs laser mass spectrometry can be a sensitive tool to identify and quantify volatile organic compounds in human breath.

Development of a protocol to measure volatile organic compounds in human breath: a comparison of rebreathing and on-line single exhalations using proton transfer reaction mass spectrometry

Analysis of volatile organic compounds (VOCs) on human breath has great potential as a non-invasive diagnostic technique. It is, therefore, surprising that no single, standard procedure has evolved for breath sampling. Here we present a novel repeated-cycle isothermal rebreathing method, where one cycle comprises five rebreaths, which could be adopted for breath analysis of VOCs. For demonstration purposes, we present measurements of three common breath VOCs: isoprene, acetone and methanol. Their concentrations measured in breath are shown to increase with number of rebreaths until a plateau value is reached by at least 20 rebreaths. The average ratio of plateau concentration to single mixed expired breath concentration was found to be 1.92 ± 0.57 for isoprene, 1.25 ± 0.13 for acetone and 1.12 ± 0.12 for methanol (mean ± standard deviation). Measurements from on-line single exhalations are presented which demonstrate a positive slope in the time-dependent expirograms of isoprene and acetone. The slope of the isoprene expirogram is persistently linear and the end-expired concentration of isoprene is highly variable in the same subject depending on the duration of exhalation. End-expired values of acetone are not as sensitive to the length of exhalation, and are the same to within measurement uncertainty for any duration of exhalation for any subject. It is concluded that uncontrolled single on-line exhalations are not suitable for the reliable measurement of isoprene in the breath and that rebreathing can be the basis of an easily tolerated protocol for the reliable collection of breath samples.

Development of a Multibed Sorption Trap, Comprehensive Two-Dimensional Gas Chromatography, and Time-of-Flight Mass Spectrometry System for the Analysis of Volatile Organic Compounds in Human Breath

A method for the determination of volatile organic compounds (VOCs) at sub-trace levels in breath samples based on a multibed sorption trap for the collection and concentration of VOCs, a comprehensive multidimensional gas chromatograph (GCxGC) for the separation of complex mixtures, and a time-of-flight mass spectrometer detector is designed and developed. The good performance of the trap tube device developed for the concentration together with the high sensitivity and separation power of the GCxGC results in a powerful system. In the analysis of samples, more than 100 different compounds are detected of which between 65 and 85 are clearly identified. A total of approximately 250 different compounds are observed in all the samples evaluated of which 142 are identified. A preliminary study to evaluate breath biomarkers for active smoking is performed. The levels of previously described biomarkers are found to be strongly time-dependent with amounts found approximately 1 h after smoking returning to the levels found in nonsmoking volunteers. However, 2,5-dimethylfuran, 2-methylfuran, and furan are found to be effective biomarkers given that they were only found in samples taken from smokers and could still be detected more than 2 h after smoking.

Persistence of aroma compounds in human breath after consuming an aqueous model aroma mixture

Persistence of aroma compounds in the breath was studied from a model mixture containing five chemicals in an aqueous medium at two concentration levels. The breath of five subjects was monitored by atmospheric pressure ionization-mass spectrometry (API-MS) and the persistence of each compound computed as the ratio of instrumental responses between first and second breaths. Persistence was modelled, based on relevant physicochemical parameters of the compounds in the mixture. Vapour pressure was found to be the most significant parameter. Persistence was not influenced by panellists, volatile concentration levels or replications within subjects, although there were large differences in persistence among chemicals.

Application of low-temperature glassy carbon-coated macrofibers for solid-phase microextraction analysis of simulated breath volatiles.

With increasing interest in the detection of disease-related volatile organic compounds (VOCs) found in human breath, breath analysis could prove to be a very useful diagnostic tool, especially for the early detection of lung cancer. Solid-phase microextraction (SPME) is a technique well suited for breath analysis and has been applied to studying VOCs in the nanomolar concentration range. However, many compounds of interest in human breath are excreted at picomolar concentrations and may be unsuitable for analysis using conventional SPME sorbent phases. To extend the concentration range of conventional SPME, a novel 4-cm-long, low-temperature glassy carbon (LTGC) macrofiber was developed. The LTGC SPME macrofibers were used to extract five lung cancer-related VOCs (2-methylheptane, styrene, propylbenzene, decane, undecane) at conditions simulating human breath, and they were analyzed via gas chromatography/mass spectrometry. Results show that detection limits are lower using the SPME macrofibers compared to a conventional SPME fiber, in the low- to sub-picomolar range for the compounds of interest, which should be adequate for the analysis of these compounds in human breath. Also, the LTGC SPME macrofibers demonstrate significantly greater extraction efficiencies, sensitivity, and peak identification accuracy compared to that of commercial PDMS/DVB fibers without excessive chromatographic peak broadening. The use of SPME macrofibers broadens the potential range of application of SPME where the rapid extraction of very low levels of volatile compounds is required.